Trial Outcomes & Findings for Vitamin D3 in Systemic Lupus Erythematosus (NCT NCT00710021)

NCT ID: NCT00710021

Last Updated: 2017-04-26

Results Overview

Presence of an Interferon (IFN) Alpha signature response is defined as: a reduction in expression from baseline (Screening) of at least 50% for 1 of 3 IFN Alpha responsive genes (Ifit1, Ifi44, Mx1) with concurrent expression in the remaining 2 genes at a level not more than 25% above baseline, or a reduction in expression from baseline of at least 25% for 2 of the 3 IFN Alpha responsive genes with concurrent expression in the third gene at a level of no more than 25% above baseline. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were considered as response failures during calculation.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 57 participants
• Primary outcome timeframe: 0, Week 12
• Results posted on: 2017-04-26

Participant Flow

Participant milestones

Measure	Placebo Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).	Vitamin D3 4000 IU Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).
Overall Study STARTED	19	19	19
Overall Study Modified Intent-to-Treat (mITT)	19	17	18
Overall Study COMPLETED	18	16	18
Overall Study NOT COMPLETED	1	3	1

Reasons for withdrawal

Measure	Placebo Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).	Vitamin D3 4000 IU Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).
Overall Study Lost to Follow-up	1	0	0
Overall Study Subject's Decision	0	1	0
Overall Study Subject misrandomized	0	1	1
Overall Study Physician Decision	0	1	0

Baseline Characteristics

Vitamin D3 in Systemic Lupus Erythematosus

Baseline characteristics by cohort

Measure	Placebo n=19 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=17 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Total n=54 Participants Total of all reporting groups
Age, Continuous	38.7 years STANDARD_DEVIATION 12.3 • n=93 Participants	36.5 years STANDARD_DEVIATION 10.9 • n=4 Participants	38.3 years STANDARD_DEVIATION 12.9 • n=27 Participants	37.9 years STANDARD_DEVIATION 11.9 • n=483 Participants
Sex: Female, Male Female	18 Participants n=93 Participants	17 Participants n=4 Participants	16 Participants n=27 Participants	51 Participants n=483 Participants
Sex: Female, Male Male	1 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants	3 Participants n=483 Participants
Region of Enrollment United States	19 participants n=93 Participants	17 participants n=4 Participants	18 participants n=27 Participants	54 participants n=483 Participants
Years with Systemic Lupus Erythematosus (SLE) at Baseline	10.9 years STANDARD_DEVIATION 7.8 • n=93 Participants	10.0 years STANDARD_DEVIATION 7.8 • n=4 Participants	8.7 years STANDARD_DEVIATION 6.0 • n=27 Participants	9.9 years STANDARD_DEVIATION 7.1 • n=483 Participants
Number of American College of Rheumatology (ACR) Criteria met at Screening	5.4 number of criteria met STANDARD_DEVIATION 1.3 • n=93 Participants	5.5 number of criteria met STANDARD_DEVIATION 1.1 • n=4 Participants	5.8 number of criteria met STANDARD_DEVIATION 1.3 • n=27 Participants	5.6 number of criteria met STANDARD_DEVIATION 1.2 • n=483 Participants
Modified SELENA-SLEDAI Score	2.9 score STANDARD_DEVIATION 1.2 • n=93 Participants	2.7 score STANDARD_DEVIATION 1.2 • n=4 Participants	2.6 score STANDARD_DEVIATION 1.0 • n=27 Participants	2.7 score STANDARD_DEVIATION 1.1 • n=483 Participants

PRIMARY outcome

Timeframe: 0, Week 12

Population: Modified Intent-to-Treat. Although presence of a positive IFN Alpha Signature at the Screening visit was an entry criterion for the study, 8 subjects (4 Placebo, 2 Vitamin D3 2000 IU, 2 Vitamin D3 4000 IU ) who did not have a signature were included in the study.

Presence of an Interferon (IFN) Alpha signature response is defined as: a reduction in expression from baseline (Screening) of at least 50% for 1 of 3 IFN Alpha responsive genes (Ifit1, Ifi44, Mx1) with concurrent expression in the remaining 2 genes at a level not more than 25% above baseline, or a reduction in expression from baseline of at least 25% for 2 of the 3 IFN Alpha responsive genes with concurrent expression in the third gene at a level of no more than 25% above baseline. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were considered as response failures during calculation.

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=35 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=19 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=17 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
Percent of Participants With an IFN Alpha Signature Response at Week 12	25.7 Percent of participants	27.8 Percent of participants	36.8 Percent of participants	23.5 Percent of participants

SECONDARY outcome

Timeframe: 0, Week 6

Population: Modified Intent-to-Treat. Although presence of a positive IFN Alpha Signature at the Screening visit was an entry criterion for the study, 8 subjects (4 Placebo, 2 Vitamin D3 2000 IU, 2 Vitamin D3 4000 IU ) who did not have a signature were included in the study.

Presence of an Interferon (IFN) Alpha signature response is defined as: a reduction in expression from baseline (Screening) of at least 50% for 1 of 3 IFN Alpha responsive genes (Ifit1, Ifi44, Mx1) with concurrent expression in the remaining 2 genes at a level not more than 25% above baseline, or a reduction in expression from baseline of at least 25% for 2 of the 3 IFN Alpha responsive genes with concurrent expression in the third gene at a level of no more than 25% above baseline. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were considered as response failures during calculation.

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=35 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=19 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=17 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
Percent of Participants With an IFN Alpha Signature Response at Week 6	11.4 Percent of participants	5.6 Percent of participants	36.8 Percent of participants	17.6 Percent of participants

SECONDARY outcome

Timeframe: 0, Week 12

Population: Modified Intent-to-Treat. Although presence of a positive IFN Alpha Signature at the Screening visit was an entry criterion for the study, 8 subjects (4 Placebo, 2 Vitamin D3 2000 IU, 2 Vitamin D3 4000 IU) who did not have a signature were included in the study.

An Interferon (IFN) Alpha signature is defined as: expression of Mx1, Ifit1, or Ifi44 at a level greater than or equal to 4 standard deviations above the mean of a set of normal controls, or expression of 2 of the 3 genes at a level greater than or equal to 2 standard deviations above the mean of a set of normal controls. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were assumed as signatures during calculation.

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=35 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=19 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=17 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
Percent of Participants With IFN Alpha Signature at Week 12	97.1 Percent of participants	100.0 Percent of participants	78.9 Percent of participants	94.1 Percent of participants

SECONDARY outcome

Timeframe: Week 6

Population: Modified Intent-to-Treat. Although presence of a positive IFN Alpha Signature at the Screening visit was an entry criterion for the study, 8 subjects (4 Placebo, 2 Vitamin D3 2000 IU, 2 Vitamin D3 4000 IU) who did not have a signature were included in the study.

An Interferon (IFN) Alpha signature is defined as: expression of Mx1, Ifit1, or Ifi44 at a level greater than or equal to 4 standard deviations above the mean of a set of normal controls, or expression of 2 of the 3 genes at a level greater than or equal to 2 standard deviations above the mean of a set of normal controls. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were assumed as signatures during calculation.

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=35 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=19 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=17 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
Percent of Participants With IFN Alpha Signature at Week 6	97.1 Percent of participants	100.0 Percent of participants	84.2 Percent of participants	94.1 Percent of participants

SECONDARY outcome

Timeframe: 0, Week 12

Population: Modified Intent-to-Treat with available data

The Ifit1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. This gene encodes an interferon-induced protein with tetratricopeptide repeats. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 12 is represented as a negative value (and vice versa).

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=33 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=15 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=15 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 12	1.5 qRT-PCR fold change Standard Deviation 45.3	5.2 qRT-PCR fold change Standard Deviation 33.9	-8.6 qRT-PCR fold change Standard Deviation 40.5	-2.9 qRT-PCR fold change Standard Deviation 57.0

SECONDARY outcome

Timeframe: 0, Week 6

Population: Modified Intent-to-Treat with available data

The Ifit1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes an interferon-induced protein with tetratricopeptide repeats. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 6 is represented as a negative value (and vice versa).

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=30 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=17 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=16 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=13 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
qRT-PCR Fold Change in Ifit1 Gene Expression From Baseline to Week 6	-1.4 qRT-PCR fold change Standard Deviation 28.0	6.3 qRT-PCR fold change Standard Deviation 18.1	-15.5 qRT-PCR fold change Standard Deviation 38.0	-11.6 qRT-PCR fold change Standard Deviation 35.5

SECONDARY outcome

Timeframe: 0, Week 12

Population: Modified Intent-to-Treat with available data

The Ifi44 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes interferon-induced protein 44. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 12 is represented as a negative value (and vice versa).

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=33 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=15 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=15 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
qRT-PCR Fold Change in Ifi44 Gene Expression From Baseline to Week 12	1.4 qRT-PCR fold change Standard Deviation 10.8	2.9 qRT-PCR fold change Standard Deviation 11.7	-2.5 qRT-PCR fold change Standard Deviation 16.4	-0.3 qRT-PCR fold change Standard Deviation 9.8

SECONDARY outcome

Timeframe: 0, Week 6

Population: Modified Intent-to-Treat with available data

The Ifi44 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes interferon-induced protein 44. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 6 is represented as a negative value (and vice versa).

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=30 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=17 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=16 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=13 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
qRT-PCR Fold Change in Ifi44 Gene Expression From Baseline to Week 6	0.3 qRT-PCR fold change Standard Deviation 9.4	4.1 qRT-PCR fold change Standard Deviation 5.9	-3.9 qRT-PCR fold change Standard Deviation 12.8	-4.6 qRT-PCR fold change Standard Deviation 11.0

SECONDARY outcome

Timeframe: 0, Week 12

Population: Modified Intent-to-Treat with available data

The Mx1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes for the homolog of mouse myxovirus (influenza virus) resistance 1 protein. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 12 is represented as a negative value (and vice versa).

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=33 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=15 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=15 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
qRT-PCR Fold Change in Mx1 Gene Expression From Baseline to Week 12	3.5 qRT-PCR fold change Standard Deviation 11.9	4.8 qRT-PCR fold change Standard Deviation 11.6	-1.6 qRT-PCR fold change Standard Deviation 14.0	2.0 qRT-PCR fold change Standard Deviation 12.5

SECONDARY outcome

Timeframe: 0, Week 6

Population: Modified Intent-to-Treat with available data

The Mx1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes for the homolog of mouse myxovirus (influenza virus) resistance 1 protein. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 6 is represented as a negative value (and vice versa).

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=30 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=17 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=16 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=13 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
qRT-PCR Fold Change in Mx1 Gene Expression From Baseline to Week 6	1.0 qRT-PCR fold change Standard Deviation 13.5	0.7 qRT-PCR fold change Standard Deviation 6.7	-4.8 qRT-PCR fold change Standard Deviation 10.5	1.4 qRT-PCR fold change Standard Deviation 19.5

SECONDARY outcome

Timeframe: 0, Week 12

Population: Modified Intent-to-Treat with available data

C3 is a blood test that measures the activity of the complement component 3 (C3) protein. The normal C3 range is 75 to 135 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C3. A decrease in C3 level over time may indicate disease activity. An increase in C3 from baseline to Week 12 is represented as a positive value (and vice versa).

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=34 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=18 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=16 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
Change in Serum C3 Level From Baseline to Week 12	1.9 mg/dL Standard Deviation 11.0	2.9 mg/dL Standard Deviation 11.1	1.8 mg/dL Standard Deviation 16.1	0.7 mg/dL Standard Deviation 11.1

SECONDARY outcome

Timeframe: 0, Week 6

Population: Modified Intent-to-Treat with available data

C3 is a blood test that measures the activity of the complement component 3 (C3) protein. The normal C3 range is 75 to 135 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C3. A decrease in C3 level over time may indicate disease activity. An increase in C3 from baseline to Week 6 is represented as a positive value (and vice versa).

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=33 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=19 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=15 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
Change in Serum C3 Level From Baseline to Week 6	3.8 mg/dL Standard Deviation 10.5	3.7 mg/dL Standard Deviation 10.3	3.3 mg/dL Standard Deviation 10.9	3.8 mg/dL Standard Deviation 11.2

SECONDARY outcome

Timeframe: 0, Week 12

Population: Modified Intent-to-Treat with available data

C4 is a blood test that measures the activity of the complement component 4 (C4) protein. The normal range for males is 12 to 72 mg/dL and the normal range for females is 13 to 75 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C4. A decrease in C4 level over time may indicate disease activity. An increase in C4 from baseline to Week 12 is represented as a positive value (and vice versa).

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=34 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=18 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=16 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
Change in Serum C4 Level From Baseline to Week 12	.9 mg/dL Standard Deviation 3.9	1.9 mg/dL Standard Deviation 4.4	0.2 mg/dL Standard Deviation 2.5	-0.3 mg/dL Standard Deviation 2.9

SECONDARY outcome

Timeframe: 0, Week 6

Population: Modified Intent-to-Treat with available data

Outcome measure description: C4 is a blood test that measures the activity of the complement component 4 (C4) protein. The normal range for males is 12 to 72 mg/dL and the normal range for females is 13 to 75 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C4. A decrease in C4 level over time may indicate disease activity. An increase in C4 from baseline to Week 6 is represented as a positive value (and vice versa).

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=33 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=19 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=15 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
Change in Serum C4 Level From Baseline to Week 6	-0.2 mg/dL Standard Deviation 2.7	0.4 mg/dL Standard Deviation 2.8	0.3 mg/dL Standard Deviation 3.3	-0.8 mg/dL Standard Deviation 2.7

SECONDARY outcome

Timeframe: 0, Week 12

Population: Modified Intent-to-Treat with available data

Patients with systemic lupus erythematosus (SLE) may have autoantibodies (e.g., self against self) to double-stranded DNA. Double-stranded DNA is one of multiple diagnostic tests for SLE and levels may be associated with disease activity. A positive test for autoantibodies to double-stranded DNA is based on the normal range from the local laboratory. Change in status (+ or -) from baseline is evaluated.

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=34 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=17 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=16 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12 Positive at Baseline, Positive at Week 12	88.2 Percent of participants	77.8 Percent of participants	94.1 Percent of participants	100.0 Percent of participants
Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12 Positive at Baseline, Negative at Week 12	6.0 Percent of participants	11.0 Percent of participants	0.0 Percent of participants	0.0 Percent of participants
Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12 Negative at Baseline, Positive at Week 12	2.9 Percent of participants	5.6 Percent of participants	0.0 Percent of participants	0.0 Percent of participants
Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 12 Negative at Baseline, Negative at Week 12	2.9 Percent of participants	5.6 Percent of participants	5.9 Percent of participants	0.0 Percent of participants

SECONDARY outcome

Timeframe: 0, Week 6

Population: Modified Intent-to-Treat with available data

Patients with systemic lupus erythematosus (SLE) may have autoantibodies (e.g., self against self) to double-stranded DNA. Double-stranded DNA is one of multiple diagnostic tests for SLE and levels may be associated with disease activity. A positive test for autoantibodies to double-stranded DNA is based on the normal range from the local laboratory. Change in status (+ or -) from baseline is evaluated.

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=34 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=19 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=16 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6 Positive at Baseline, Positive at Week 6	91.2 Percent of participants	88.9 Percent of participants	94.7 Percent of participants	93.7 Percent of participants
Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6 Positive at Baseline, Negative at Week 6	2.9 Percent of participants	0.0 Percent of participants	0.0 Percent of participants	6.3 Percent of participants
Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6 Negative at Baseline, Positive at Week 6	0.0 Percent of participants	0.0 Percent of participants	0.0 Percent of participants	0.0 Percent of participants
Change in Status for Anti-double-stranded DNA Autoantibody From Baseline to Week 6 Negative at Baseline, Negative at Week 6	5.9 Percent of participants	11.1 Percent of participants	5.3 Percent of participants	0.0 Percent of participants

SECONDARY outcome

Timeframe: 0, Week 12

Population: Modified Intent-to-Treat with available data

The modified Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus (SLE) Disease Activity Index (SELENA-SLEDAI) score is a weighted scale score ranging from 0 to 105 based on the presence or absence of 24 manifestations of SLE. The SELENA-SLEDAI assesses disease activity for 10 days prior to and including the day of assessment. For this study, the SELENA-SLEDAI score was modified to include proteinuria defined by dipstick rather than 24 hour urine. Positive change in the SELENA-SLEDAI score indicate increased disease activity.

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=34 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=18 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=16 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
Change in SELENA-SLEDAI Total Score From Baseline to Week 12	0.2 Change in Scores on a Scale Standard Deviation 1.8	0.2 Change in Scores on a Scale Standard Deviation 1.9	0.0 Change in Scores on a Scale Standard Deviation 0.7	0.2 Change in Scores on a Scale Standard Deviation 1.8

SECONDARY outcome

Timeframe: Week 12

Population: Modified Intent-to-Treat with available data

The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Cardiorespiratory-specific" body system.

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=34 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=18 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=16 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
Cardiorespiratory BILAG Status at Week 12	2.9 Percent with grade A or B	0.0 Percent with grade A or B	0.0 Percent with grade A or B	6.3 Percent with grade A or B

SECONDARY outcome

Timeframe: Week 12

Population: Modified Intent-to-Treat with available data

The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Constitutional-specific" body system.

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=34 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=18 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=16 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
Constitutional BILAG Status at Week 12	0.0 Percent with grade A or B	0.0 Percent with grade A or B	0.0 Percent with grade A or B	0.0 Percent with grade A or B

SECONDARY outcome

Timeframe: Week 12

Population: Modified Intent-to-Treat with available data

The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Gastrointestinal-specific" body system.

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=34 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=18 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=16 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
Gastrointestinal BILAG Status at Week 12	0.0 Percent with grade A or B	0.0 Percent with grade A or B	0.0 Percent with grade A or B	0.0 Percent with grade A or B

SECONDARY outcome

Timeframe: Week 12

Population: Modified Intent-to-Treat with available data

The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Hematological-specific" body system.

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=34 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=18 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=16 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
Hematological BILAG Status at Week 12	0.0 Percent with grade A or B	0.0 Percent with grade A or B	0.0 Percent with grade A or B	0.0 Percent with grade A or B

SECONDARY outcome

Timeframe: Week 12

Population: Modified Intent-to-Treat with available data

The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Mucocutaneous-specific" body system.

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=34 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=18 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=16 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
Mucocutaneous BILAG Status at Week 12	5.9 Percent with grade A or B	0.0 Percent with grade A or B	5.6 Percent with grade A or B	12.5 Percent with grade A or B

SECONDARY outcome

Timeframe: Week 12

Population: Modified Intent-to-Treat with available data

Outcome measure description: The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Musculoskeletal-specific" body system.

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=34 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=18 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=16 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
Musculoskeletal BILAG Status at Week 12	5.9 Percent with grade A or B	11.1 Percent with grade A or B	5.6 Percent with grade A or B	0.0 Percent with grade A or B

SECONDARY outcome

Timeframe: Week 12

Population: Modified Intent-to-Treat with available data

The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Neuropsychiatric-specific" body system.

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=34 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=18 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=16 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
Neuropsychiatric BILAG Status at Week 12	0.0 Percent with grade A or B	0.0 Percent with grade A or B	0.0 Percent with grade A or B	0.0 Percent with grade A or B

SECONDARY outcome

Timeframe: Week 12

Population: Modified Intent-to-Treat with available data

The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Ophthalmic-specific" body system.

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=34 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=18 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=16 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
Ophthalmic BILAG Status at Week 12	0.0 Percent with grade A or B	0.0 Percent with grade A or B	0.0 Percent with grade A or B	0.0 Percent with grade A or B

SECONDARY outcome

Timeframe: Week 12

Population: Modified Intent-to-Treat with available data

The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Renal-specific" body system.

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=34 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=18 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=16 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
Renal BILAG Status at Week 12	0.0 Percent with grade A or B	0.0 Percent with grade A or B	0.0 Percent with grade A or B	0.0 Percent with grade A or B

SECONDARY outcome

Timeframe: From start of study treatment through Week 12

Population: Safety

Grades are based on National Cancer Institute--Common Terminology Criteria (NCI-CTCAE) Version 3.0 over the duration of the study. Participants who experienced at least one grade 3 or higher adverse event (AE) are counted only once. The adverse events are treatment-emergent, which means that the AE occurred after taking the first dose of study drug.

Outcome measures

Measure	Vitamin D3 2000 and 4000 IU (Pooled ) n=35 Participants This is a statistically pooled group of those participants randomized to either vitamin D3 2,000 IU or vitamin D3 4,000 IU treatment (e.g., pooled group for statistical analysis purposes only).	Vitamin D3 4000 IU n=18 Participants Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).	Placebo n=19 Participants Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=17 Participants Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).
Percent of Participants With Adverse Events of Grade 3 or Above	22.9 Percent of participants	22.2 Percent of participants	5.3 Percent of participants	23.5 Percent of participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Vitamin D3 2000 IU

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Vitamin D3 4000 IU

Serious events: 3 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=19 participants at risk Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=17 participants at risk Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).	Vitamin D3 4000 IU n=18 participants at risk Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).
Infections and infestations Cellulitis	0.00% 0/19 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	0.00% 0/17 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.6% 1/18 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Infections and infestations Sinusitis	0.00% 0/19 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	0.00% 0/17 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.6% 1/18 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	0.00% 0/19 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	0.00% 0/17 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.6% 1/18 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Nervous system disorders Cerebrovascular accident	0.00% 0/19 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	0.00% 0/17 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.6% 1/18 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Vascular disorders Hypertension	0.00% 0/19 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	0.00% 0/17 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.6% 1/18 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Vascular disorders Hypertensive emergency	0.00% 0/19 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	0.00% 0/17 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.6% 1/18 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)

Other adverse events

Measure	Placebo n=19 participants at risk Participants received a 12-week course of oral vitamin D3-placebo (cholecalciferol placebo, 1 dose daily).	Vitamin D3 2000 IU n=17 participants at risk Participants received a 12-week course of oral Vitamin D3 (cholecalciferol, 2,000 international units \[IU\] daily).	Vitamin D3 4000 IU n=18 participants at risk Participants received a 12-week course of oral vitamin D3 (cholecalciferol, 4,000 IU daily).
Blood and lymphatic system disorders Anaemia	0.00% 0/19 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	17.6% 3/17 • Number of events 3 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	16.7% 3/18 • Number of events 3 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Blood and lymphatic system disorders Lymphopenia	10.5% 2/19 • Number of events 2 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.9% 1/17 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.6% 1/18 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Gastrointestinal disorders Diarrhoea	10.5% 2/19 • Number of events 2 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	0.00% 0/17 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.6% 1/18 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Infections and infestations Upper respiratory tract infection	0.00% 0/19 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	0.00% 0/17 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	22.2% 4/18 • Number of events 4 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Investigations Blood albumin decreased	5.3% 1/19 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.9% 1/17 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.6% 1/18 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Investigations Blood creatinine increased	0.00% 0/19 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	11.8% 2/17 • Number of events 2 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.6% 1/18 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Investigations Blood glucose decreased	10.5% 2/19 • Number of events 2 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.9% 1/17 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	0.00% 0/18 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Investigations Blood potassium decreased	21.1% 4/19 • Number of events 4 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.9% 1/17 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.6% 1/18 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Investigations Haemoglobin decreased	21.1% 4/19 • Number of events 4 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	17.6% 3/17 • Number of events 3 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	27.8% 5/18 • Number of events 5 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Investigations Lymphocyte count decreased	15.8% 3/19 • Number of events 3 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.9% 1/17 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	11.1% 2/18 • Number of events 2 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Investigations Neutrophil count decreased	10.5% 2/19 • Number of events 2 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	17.6% 3/17 • Number of events 3 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	27.8% 5/18 • Number of events 5 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Investigations White blood cell count decreased	31.6% 6/19 • Number of events 7 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	11.8% 2/17 • Number of events 2 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	27.8% 5/18 • Number of events 5 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/19 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	11.8% 2/17 • Number of events 2 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.6% 1/18 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Metabolism and nutrition disorders Hypoalbuminaemia	5.3% 1/19 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	0.00% 0/17 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	16.7% 3/18 • Number of events 3 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/19 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	11.8% 2/17 • Number of events 2 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	11.1% 2/18 • Number of events 2 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/19 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	11.8% 2/17 • Number of events 2 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.6% 1/18 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/19 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	11.8% 2/17 • Number of events 2 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.6% 1/18 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Musculoskeletal and connective tissue disorders Back pain	10.5% 2/19 • Number of events 2 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	0.00% 0/17 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.6% 1/18 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	15.8% 3/19 • Number of events 3 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	11.8% 2/17 • Number of events 2 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.6% 1/18 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Renal and urinary disorders Lupus nephritis	5.3% 1/19 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.9% 1/17 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.6% 1/18 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Skin and subcutaneous tissue disorders Cutaneous lupus erythematosus	5.3% 1/19 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.9% 1/17 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	5.6% 1/18 • Number of events 1 • Baseline to 12 weeks This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)

Additional Information

Director, Clinical Research Operations Program

DAIT/NIAID

Phone: 301-594-7669

Email: DAITClinicalTrialsGov@niaid.nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place