Trial Outcomes & Findings for Atorvastatin in New Onset Type 1 Diabetes Mellitus (T1DM) (NCT NCT00529191)

Results Overview

The change in C-peptide measurements collected over a 4 hour period (0, 30, 60, 90, 120, 150, 180, 210 and 240 minutes) after a Mixed Meal Tolerance Test at baseline vs 12 months post-treatment were calculated. The area under the curve for these combined measurements is calculated and the unit of measure is nanogram x minutes / mL. Efficacy (success) is defined by \< 7.5% reduction in AUC for 4-hr MMTT.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

40 participants

Primary outcome timeframe

Baseline vs 12-month

Results posted on

2017-03-13

Participant Flow

Patients were recruited from medical clinics at CHOP from July 2007- January 2010

Participant milestones

Participant milestones
Measure	Atorvastatin Two out of every 3 patients will receive atorvastatin in tablet form. The subject will start on 10mg of atorvastatin daily for four weeks, and then titrate up to 20mg daily. There will be 12 months of treatment followed by 6 months of a washout period.	Placebo Placebo treated. Patients will receive tablets daily.There will be 12 months of treatment followed by 6 months of a washout period.
Overall Study STARTED	27	13
Overall Study COMPLETED	24	13
Overall Study NOT COMPLETED	3	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Atorvastatin in New Onset Type 1 Diabetes Mellitus (T1DM)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Atorvastatin n=27 Participants Two out of every 3 patients will receive atorvastatin.	Placebo n=13 Participants Placebo treatment	Total n=40 Participants Total of all reporting groups
Age, Categorical <=18 years	26 Participants n=5 Participants	12 Participants n=7 Participants	38 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	13.38 years STANDARD_DEVIATION 1.96 • n=5 Participants	13.30 years STANDARD_DEVIATION 2.03 • n=7 Participants	13.33 years STANDARD_DEVIATION 2.055 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	9 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	4 Participants n=7 Participants	20 Participants n=5 Participants
Region of Enrollment United States	27 participants n=5 Participants	13 participants n=7 Participants	40 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline vs 12-month

Population: Participants who completed their 12-month treatment were included in the analysis, in which the change in C-peptide AUC at baseline and 12-months were calculated. Efficacy (success) is defined by \< 7.5% reduction in AUC for 4-hr MMTT.

The change in C-peptide measurements collected over a 4 hour period (0, 30, 60, 90, 120, 150, 180, 210 and 240 minutes) after a Mixed Meal Tolerance Test at baseline vs 12 months post-treatment were calculated. The area under the curve for these combined measurements is calculated and the unit of measure is nanogram x minutes / mL. Efficacy (success) is defined by \< 7.5% reduction in AUC for 4-hr MMTT.

Outcome measures

Outcome measures
Measure	Atorvastatin n=27 Participants Two out of every 3 patients will receive atorvastatin.	Placebo n=13 Participants Placebo treatment	Atorvastatin YES Islet Cell Preservation Two out of every three patients will receive atorvastatin. Atorvastatin: Pill, initially at 10 mg, then after 4 weeks, 20 mg Once daily for a total of 12 months	Placebo YES Islet Cell Preservation Placebo treated. Patients will receive tablets daily.There will be 12 months of treatment followed by 6 months of a washout period.
Efficacy of a Daily Dose of Atorvastatin to Maintain Islet Cell Function as Measured by a 4-hour C-peptide Area Under Curve (AUC) in Patients With Newly Diagnosed Type 1 Diabetes Mellitus	345 nanogram*minutes/ml Standard Deviation 679	178 nanogram*minutes/ml Standard Deviation 308	—	—

SECONDARY outcome

Timeframe: Baseline vs 12 months

The C-peptide AUC measurements are collected over a 2 hour period (with 30 minute intervals) after a Mixed Meal Tolerance Test. The area under the curve from these combined measurements (from 0 to 120 or 0 to 240 minutes) is calculated and the unit of measure is nanogram\*minutes/ml. The change in C-peptide AUC in response to a 2 hour MMTT at baseline vs 12 months were calculated, and efficacy (success) is defined as \< 7.5% reduction.

Outcome measures

Outcome measures
Measure	Atorvastatin n=27 Participants Two out of every 3 patients will receive atorvastatin.	Placebo n=13 Participants Placebo treatment	Atorvastatin YES Islet Cell Preservation Two out of every three patients will receive atorvastatin. Atorvastatin: Pill, initially at 10 mg, then after 4 weeks, 20 mg Once daily for a total of 12 months	Placebo YES Islet Cell Preservation Placebo treated. Patients will receive tablets daily.There will be 12 months of treatment followed by 6 months of a washout period.
% Subjects Without Change in 2-hour C-peptide AUC in Response to the MMTT at Baseline vs. 12 Months	14.8 % of participants with efficacy	38.4 % of participants with efficacy	—	—

SECONDARY outcome

Timeframe: Visit 1, 2, 3, 4, 5, 6, 7

Mean daily insulin dose per kg body weight for the 1 week preceding each scheduled study visit.

Outcome measures

Outcome measures
Measure	Atorvastatin n=27 Participants Two out of every 3 patients will receive atorvastatin.	Placebo n=13 Participants Placebo treatment	Atorvastatin YES Islet Cell Preservation Two out of every three patients will receive atorvastatin. Atorvastatin: Pill, initially at 10 mg, then after 4 weeks, 20 mg Once daily for a total of 12 months	Placebo YES Islet Cell Preservation Placebo treated. Patients will receive tablets daily.There will be 12 months of treatment followed by 6 months of a washout period.
Mean Daily Insulin Dose Per kg Body Weight for 7 Days Visit 1	0.53 units/kg Standard Deviation 0.26	0.62 units/kg Standard Deviation 0.26	—	—
Mean Daily Insulin Dose Per kg Body Weight for 7 Days Visit 2	0.50 units/kg Standard Deviation 0.25	0.52 units/kg Standard Deviation 0.22	—	—
Mean Daily Insulin Dose Per kg Body Weight for 7 Days Visit 3	0.48 units/kg Standard Deviation 0.21	0.50 units/kg Standard Deviation 0.26	—	—
Mean Daily Insulin Dose Per kg Body Weight for 7 Days Visit 4	0.59 units/kg Standard Deviation 0.21	0.47 units/kg Standard Deviation 0.30	—	—
Mean Daily Insulin Dose Per kg Body Weight for 7 Days Visit 5	0.64 units/kg Standard Deviation 0.22	0.59 units/kg Standard Deviation 0.35	—	—
Mean Daily Insulin Dose Per kg Body Weight for 7 Days Visit 6	0.65 units/kg Standard Deviation 0.24	0.64 units/kg Standard Deviation 0.36	—	—
Mean Daily Insulin Dose Per kg Body Weight for 7 Days Visit 7	0.70 units/kg Standard Deviation 0.35	0.71 units/kg Standard Deviation 0.34	—	—

SECONDARY outcome

Timeframe: 3, 6, 9, 12, and 18 months

Outcome measures

Outcome measures
Measure	Atorvastatin n=27 Participants Two out of every 3 patients will receive atorvastatin.	Placebo n=13 Participants Placebo treatment	Atorvastatin YES Islet Cell Preservation Two out of every three patients will receive atorvastatin. Atorvastatin: Pill, initially at 10 mg, then after 4 weeks, 20 mg Once daily for a total of 12 months	Placebo YES Islet Cell Preservation Placebo treated. Patients will receive tablets daily.There will be 12 months of treatment followed by 6 months of a washout period.
Levels of HbA1c at Months 3, 6, 9, 12 and 18 3 months	6.68 percentage of glycated hemoglobin Standard Deviation 0.95	6.39 percentage of glycated hemoglobin Standard Deviation 0.95	—	—
Levels of HbA1c at Months 3, 6, 9, 12 and 18 6 months	7.13 percentage of glycated hemoglobin Standard Deviation 0.90	6.62 percentage of glycated hemoglobin Standard Deviation 1.22	—	—
Levels of HbA1c at Months 3, 6, 9, 12 and 18 9 months	7.47 percentage of glycated hemoglobin Standard Deviation 1.44	6.86 percentage of glycated hemoglobin Standard Deviation 0.91	—	—
Levels of HbA1c at Months 3, 6, 9, 12 and 18 12 months	7.38 percentage of glycated hemoglobin Standard Deviation 1.19	7.26 percentage of glycated hemoglobin Standard Deviation 1.45	—	—
Levels of HbA1c at Months 3, 6, 9, 12 and 18 18 months	8.04 percentage of glycated hemoglobin Standard Deviation 1.82	7.94 percentage of glycated hemoglobin Standard Deviation 2.62	—	—

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 18

Population: All participants contributing data

Blood glucose control as determined from home glucose meter downloads for the 1 week preceding the visit. The number of subjects with hypoglycemic episodes requiring treatment (BG \< 70 mg/dl)

Outcome measures

Outcome measures
Measure	Atorvastatin n=27 Participants Two out of every 3 patients will receive atorvastatin.	Placebo n=13 Participants Placebo treatment	Atorvastatin YES Islet Cell Preservation Two out of every three patients will receive atorvastatin. Atorvastatin: Pill, initially at 10 mg, then after 4 weeks, 20 mg Once daily for a total of 12 months	Placebo YES Islet Cell Preservation Placebo treated. Patients will receive tablets daily.There will be 12 months of treatment followed by 6 months of a washout period.
Blood Glucose Control (Number of Participants With Hypoglycemia) Baseline	16 Participants	7 Participants	—	—
Blood Glucose Control (Number of Participants With Hypoglycemia) 12 Month	16 Participants	9 Participants	—	—
Blood Glucose Control (Number of Participants With Hypoglycemia) 18 Month	8 Participants	8 Participants	—	—

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 18

Population: All subjects contributing data

number of episodes of hypoglycemia requiring any treatment, defined by the need for treatment with glucagon or third party intervention.

Outcome measures

Outcome measures
Measure	Atorvastatin n=27 Participants Two out of every 3 patients will receive atorvastatin.	Placebo n=13 Participants Placebo treatment	Atorvastatin YES Islet Cell Preservation Two out of every three patients will receive atorvastatin. Atorvastatin: Pill, initially at 10 mg, then after 4 weeks, 20 mg Once daily for a total of 12 months	Placebo YES Islet Cell Preservation Placebo treated. Patients will receive tablets daily.There will be 12 months of treatment followed by 6 months of a washout period.
Number of Episodes of Hypoglycemia Requiring Any Treatment Baseline	4.13 episodes Standard Deviation 3.95	2.86 episodes Standard Deviation 3.98	—	—
Number of Episodes of Hypoglycemia Requiring Any Treatment Month 12	3.44 episodes Standard Deviation 3.01	2.44 episodes Standard Deviation 2.51	—	—
Number of Episodes of Hypoglycemia Requiring Any Treatment Month 18	2.75 episodes Standard Deviation 3.65	2.5 episodes Standard Deviation 2.2	—	—

SECONDARY outcome

Timeframe: 12 months treatment

Compliance is defined as \>=80% expected dosage consumed during the visit period.

Outcome measures

Outcome measures
Measure	Atorvastatin n=27 Participants Two out of every 3 patients will receive atorvastatin.	Placebo n=13 Participants Placebo treatment	Atorvastatin YES Islet Cell Preservation Two out of every three patients will receive atorvastatin. Atorvastatin: Pill, initially at 10 mg, then after 4 weeks, 20 mg Once daily for a total of 12 months	Placebo YES Islet Cell Preservation Placebo treated. Patients will receive tablets daily.There will be 12 months of treatment followed by 6 months of a washout period.
Study Drug Compliance Rate Overall	85.1 % of compliant participants	76.9 % of compliant participants	—	—

SECONDARY outcome

Timeframe: Baseline, Week 1, Month 3, Month 6, Month 9, Month 12,

Relationship between atorvastatin's effect on HDL and LDL cholesterol and the preservation of islet cell function. Islet cell preservation defined as: \<7.5% Reduction in C-Pep

Outcome measures

Outcome measures
Measure	Atorvastatin n=24 Participants Two out of every 3 patients will receive atorvastatin.	Placebo n=8 Participants Placebo treatment	Atorvastatin YES Islet Cell Preservation n=3 Participants Two out of every three patients will receive atorvastatin. Atorvastatin: Pill, initially at 10 mg, then after 4 weeks, 20 mg Once daily for a total of 12 months	Placebo YES Islet Cell Preservation n=5 Participants Placebo treated. Patients will receive tablets daily.There will be 12 months of treatment followed by 6 months of a washout period.
HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function Baseline- HDL Cholesterol (mg/dL)	47.58 mg/dl Standard Deviation 16.39	44.75 mg/dl Standard Deviation 18	47.33 mg/dl Standard Deviation 2.31	53.2 mg/dl Standard Deviation 16.39
HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function Baseline - LDL Cholesterol (mg/dL)	99.04 mg/dl Standard Deviation 22.37	96.13 mg/dl Standard Deviation 22.99	83.67 mg/dl Standard Deviation 25.97	99 mg/dl Standard Deviation 13.04
HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function Week 1- HDL Cholesterol (mg/dL)	45.43 mg/dl Standard Deviation 14.33	48.25 mg/dl Standard Deviation 14.26	52.33 mg/dl Standard Deviation 5.69	47.2 mg/dl Standard Deviation 13.88
HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function Week 1 - LDL Cholesterol (mg/dL)	68.91 mg/dl Standard Deviation 16.4	97.63 mg/dl Standard Deviation 17.9	57.67 mg/dl Standard Deviation 12.06	86.4 mg/dl Standard Deviation 12.46
HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function Month 3- HDL Cholesterol (mg/dL)	45.05 mg/dl Standard Deviation 14.49	48.25 mg/dl Standard Deviation 18.69	43.33 mg/dl Standard Deviation 4.04	49.25 mg/dl Standard Deviation 12.31
HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function Month 3 - LDL Cholesterol (mg/dL)	61 mg/dl Standard Deviation 20.88	106.25 mg/dl Standard Deviation 18.44	48 mg/dl Standard Deviation 12.17	91.5 mg/dl Standard Deviation 20.21
HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function Month 6- HDL Cholesterol (mg/dL)	48 mg/dl Standard Deviation 16.07	50.5 mg/dl Standard Deviation 20.7	51.67 mg/dl Standard Deviation 5.51	54.75 mg/dl Standard Deviation 19.47
HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function Month 6 - LDL Cholesterol (mg/dL)	63.1 mg/dl Standard Deviation 24.52	102.5 mg/dl Standard Deviation 16.21	54 mg/dl Standard Deviation 7	96.75 mg/dl Standard Deviation 20.93
HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function Month 9- HDL Cholesterol (mg/dL)	49.1 mg/dl Standard Deviation 14.86	45.88 mg/dl Standard Deviation 12.57	55.33 mg/dl Standard Deviation 11.15	50 mg/dl Standard Deviation 21.71
HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function Month 9 - LDL Cholesterol (mg/dL)	67.24 mg/dl Standard Deviation 24.7	97 mg/dl Standard Deviation 4.17	65.33 mg/dl Standard Deviation 28.01	90.75 mg/dl Standard Deviation 8.06
HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function Month 12 - HDL Cholesterol (mg/dL)	47.95 mg/dl Standard Deviation 14.49	45.75 mg/dl Standard Deviation 16.34	57.33 mg/dl Standard Deviation 14.15	47 mg/dl Standard Deviation 8.31
HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function Month 12 - LDL Cholesterol (mg/dL)	61.52 mg/dl Standard Deviation 20.04	102.75 mg/dl Standard Deviation 20.9	66 mg/dl Standard Deviation 23.64	96.4 mg/dl Standard Deviation 6.66

Adverse Events

Atorvastatin

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Atorvastatin n=27 participants at risk Two out of every 3 patients will receive atorvastatin.	Placebo n=13 participants at risk Placebo treatment
Endocrine disorders Hypoglycemia	11.1% 3/27 • Number of events 3 • Events were reported over the one year treatment phase of the study. Adverse events were reported or observed at interim visits, and were systematically collected.	0.00% 0/13 • Events were reported over the one year treatment phase of the study. Adverse events were reported or observed at interim visits, and were systematically collected.
Nervous system disorders Headache	25.9% 7/27 • Number of events 11 • Events were reported over the one year treatment phase of the study. Adverse events were reported or observed at interim visits, and were systematically collected.	23.1% 3/13 • Number of events 3 • Events were reported over the one year treatment phase of the study. Adverse events were reported or observed at interim visits, and were systematically collected.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	3.7% 1/27 • Number of events 1 • Events were reported over the one year treatment phase of the study. Adverse events were reported or observed at interim visits, and were systematically collected.	15.4% 2/13 • Number of events 4 • Events were reported over the one year treatment phase of the study. Adverse events were reported or observed at interim visits, and were systematically collected.
Respiratory, thoracic and mediastinal disorders Respiratory Infection	33.3% 9/27 • Number of events 11 • Events were reported over the one year treatment phase of the study. Adverse events were reported or observed at interim visits, and were systematically collected.	30.8% 4/13 • Number of events 7 • Events were reported over the one year treatment phase of the study. Adverse events were reported or observed at interim visits, and were systematically collected.
Respiratory, thoracic and mediastinal disorders Sore Throat	11.1% 3/27 • Number of events 3 • Events were reported over the one year treatment phase of the study. Adverse events were reported or observed at interim visits, and were systematically collected.	7.7% 1/13 • Number of events 2 • Events were reported over the one year treatment phase of the study. Adverse events were reported or observed at interim visits, and were systematically collected.
Gastrointestinal disorders Nausea	14.8% 4/27 • Number of events 5 • Events were reported over the one year treatment phase of the study. Adverse events were reported or observed at interim visits, and were systematically collected.	15.4% 2/13 • Number of events 2 • Events were reported over the one year treatment phase of the study. Adverse events were reported or observed at interim visits, and were systematically collected.
General disorders Fever	29.6% 8/27 • Number of events 11 • Events were reported over the one year treatment phase of the study. Adverse events were reported or observed at interim visits, and were systematically collected.	15.4% 2/13 • Number of events 2 • Events were reported over the one year treatment phase of the study. Adverse events were reported or observed at interim visits, and were systematically collected.
Gastrointestinal disorders Gastroenteritis	14.8% 4/27 • Number of events 4 • Events were reported over the one year treatment phase of the study. Adverse events were reported or observed at interim visits, and were systematically collected.	15.4% 2/13 • Number of events 2 • Events were reported over the one year treatment phase of the study. Adverse events were reported or observed at interim visits, and were systematically collected.
Gastrointestinal disorders Diarrhea	3.7% 1/27 • Number of events 1 • Events were reported over the one year treatment phase of the study. Adverse events were reported or observed at interim visits, and were systematically collected.	15.4% 2/13 • Number of events 2 • Events were reported over the one year treatment phase of the study. Adverse events were reported or observed at interim visits, and were systematically collected.

Additional Information

Steven Willi, MD

Children's Hospital of Philadelphia

Phone: 215-590-3174

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place