Trial Outcomes & Findings for Folate Supplementation in Schizophrenia (NCT NCT00249288)

NCT ID: NCT00249288

Last Updated: 2018-04-05

Results Overview

Baseline blood folate lab levels are reported by smoking status.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 46 participants
• Primary outcome timeframe: Baseline
• Results posted on: 2018-04-05

Participant Flow

Forty six participants were enrolled; 38 completed screening and 32 received study drug.

Participant milestones

Measure	Folate Participants receiving 2 mg/daily of folate, for 12 weeks	Placebo
Overall Study STARTED	19	19
Overall Study Initiated Treatment	17	15
Overall Study COMPLETED	14	14
Overall Study NOT COMPLETED	5	5

Reasons for withdrawal

Measure	Folate Participants receiving 2 mg/daily of folate, for 12 weeks	Placebo
Overall Study Lost to Follow-up	3	3
Overall Study Withdrawal by Subject	2	2

Baseline Characteristics

Folate Supplementation in Schizophrenia

Baseline characteristics by cohort

Measure	Placebo n=15 Participants Participants received 2 mg/daily of placebo, for 12 weeks	Folate n=17 Participants Patients underwent a 12 week trial of folate 2 mg/d	Total n=32 Participants Total of all reporting groups
Age, Continuous	46.5 years STANDARD_DEVIATION 11.3 • n=5 Participants	45.5 years STANDARD_DEVIATION 9.6 • n=7 Participants	46 years STANDARD_DEVIATION 10.3 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants
Region of Enrollment United States	15 participants n=5 Participants	17 participants n=7 Participants	32 participants n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	15 Participants n=5 Participants	17 Participants n=7 Participants	32 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline

Population: 1 past smoker and 1 never smoker are missing RBC folate values. For the present analysis, as opposed to a comparison of treatment groups, folate levels are compared across smoking status.

Baseline blood folate lab levels are reported by smoking status.

Outcome measures

Measure	Current Smoker n=17 Participants Study participants with current smoker status	Past Smoker n=8 Participants Participants with past smoker status	Never Smoker n=7 Participants Participants with never smoker status
Correlation Between Baseline Blood Folate and Smoking Status Serum folate, ng/ml	14.6 nanograms per milliliter Standard Deviation 3.3	14.6 nanograms per milliliter Standard Deviation 5.2	14.2 nanograms per milliliter Standard Deviation 4.1
Correlation Between Baseline Blood Folate and Smoking Status RBC folate, ng/ml	614 nanograms per milliliter Standard Deviation 142	542 nanograms per milliliter Standard Deviation 122	475 nanograms per milliliter Standard Deviation 161

PRIMARY outcome

Timeframe: Baseline

Population: One participant with CC genotype is missing RBC folate value. For the present analysis, as opposed to a comparison of treatment groups, folate levels are compared across MTHFR genotype.

Baseline blood folate lab levels are reported by MTHFR genotype.

Outcome measures

Measure	Current Smoker n=13 Participants Study participants with current smoker status	Past Smoker n=15 Participants Participants with past smoker status	Never Smoker Participants with never smoker status
Correlation Between Baseline Blood Folate and MTHFR Genotype Serum folate, ng/ml	13.3 nanograms/mL Standard Deviation 3.3	15.2 nanograms/mL Standard Deviation 4.1	—
Correlation Between Baseline Blood Folate and MTHFR Genotype RBC folate, ng/ml	624.8 nanograms/mL Standard Deviation 143.0	542.8 nanograms/mL Standard Deviation 150.6	—

PRIMARY outcome

Timeframe: Baseline

Population: All study participants at baseline. For the present analysis, as opposed to a comparison of treatment groups, folate levels are described for all participants at baseline.

Baseline blood folate lab levels and dietary intake levels are reported.

Outcome measures

Measure	Current Smoker n=32 Participants Study participants with current smoker status	Past Smoker Participants with past smoker status	Never Smoker Participants with never smoker status
Correlation Between Baseline Blood Folate Levels and Dietary Intake Serum folate, ng/ml	14.5 nanograms/mL Standard Deviation 3.9	—	—
Correlation Between Baseline Blood Folate Levels and Dietary Intake RBC folate, ng/ml	569.3 nanograms/mL Standard Deviation 148.1	—	—

PRIMARY outcome

Timeframe: Baseline score vs. week 12 score

The change from baseline to week 12 on the scale for the assessment of negative symptoms (SANS) modified total score. Total SANS scores range from 0-100. The SANS is comprised of 5 sub-scales: Affective Flattening or Blunting (score range 0-35), Alogia (score range 0-20), Avolition-Apathy (score range 0-15), Anhedonia-Asociality (score range 0-20), and Attention (0-10). For each sub-scale, the higher the score the more prominent the negative symptoms were. The total score was computed by adding all the sub-scale total scores. To compute change in scores, baseline scores were subtracted from week 12 scores, resulting in a change score. Lower values signify greater improvement (i.e. week 12 score was lower than baseline score). The SANS modified total score is the SANS total score minus the Attention subscale.

Outcome measures

Measure	Current Smoker n=14 Participants Study participants with current smoker status	Past Smoker n=14 Participants Participants with past smoker status	Never Smoker Participants with never smoker status
Efficacy of Folate Supplementation for Reducing Negative Symptoms as Measured by the SANS Modified Total	-8.5 Units on a scale Standard Deviation 7.6	-9.7 Units on a scale Standard Deviation 8.5	—

PRIMARY outcome

Timeframe: Baseline

Population: For the present analysis, as opposed to a comparison of treatment groups, B12 levels are compared across smoking status.

Baseline serum B12 lab levels are reported by smoking status.

Outcome measures

Measure	Current Smoker n=17 Participants Study participants with current smoker status	Past Smoker n=8 Participants Participants with past smoker status	Never Smoker n=7 Participants Participants with never smoker status
Correlation Between Baseline Serum B12 Levels and Smoking Status	625 picograms per milliliter Standard Deviation 273	436 picograms per milliliter Standard Deviation 130	574 picograms per milliliter Standard Deviation 160

PRIMARY outcome

Timeframe: Baseline

Population: 1 participant who have never smoker status is missing plasma homocysteine values. For the present analysis, as opposed to a comparison of treatment groups, homocysteine levels are compared across smoking status.

Baseline blood homocysteine lab levels are reported by smoking status.

Outcome measures

Measure	Current Smoker n=17 Participants Study participants with current smoker status	Past Smoker n=8 Participants Participants with past smoker status	Never Smoker n=6 Participants Participants with never smoker status
Correlation Between Baseline Homocysteine Levels and Smoking Status	9.1 micromoles per liter Standard Deviation 2.6	10.8 micromoles per liter Standard Deviation 1.6	9 micromoles per liter Standard Deviation 2.5

PRIMARY outcome

Timeframe: Baseline

Population: For the present analysis, as opposed to a comparison of treatment groups, B12 levels are compared across MTHFR genotype.

Baseline blood B12 lab levels are reported by MTHFR genotype.

Outcome measures

Measure	Current Smoker n=13 Participants Study participants with current smoker status	Past Smoker n=15 Participants Participants with past smoker status	Never Smoker Participants with never smoker status
Correlation Between Baseline Blood B12 Levels and MTHFR Genotype	605.5 picograms per milliliter Standard Deviation 312.9	557.1 picograms per milliliter Standard Deviation 170.1	—

PRIMARY outcome

Timeframe: Baseline

Population: For the present analysis, as opposed to a comparison of treatment groups, homocystein levels are compared across MTHFR genotype.

Baseline blood homocysteine lab levels are reported by MTHFR genotype.

Outcome measures

Measure	Current Smoker n=13 Participants Study participants with current smoker status	Past Smoker n=15 Participants Participants with past smoker status	Never Smoker Participants with never smoker status
Correlation Between Baseline Blood Homocysteine Levels and MTHFR Genotype	9.4 micromoles/liter Standard Deviation 2.9	9.6 micromoles/liter Standard Deviation 2.3	—

PRIMARY outcome

Timeframe: Baseline

Population: For the present analysis, as opposed to a comparison of treatment groups, B12 levels are described for all baseline participants.

Baseline serum B12 lab levels and dietary intake levels are reported.

Outcome measures

Measure	Current Smoker n=32 Participants Study participants with current smoker status	Past Smoker Participants with past smoker status	Never Smoker Participants with never smoker status
Correlation Between Baseline Serum B12 Levels and Dietary Intake	566.6 picograms/mL Standard Deviation 231.5	—	—

PRIMARY outcome

Timeframe: Baseline

Population: All study participants at baseline. For the present analysis, as opposed to a comparison of treatment groups, homocysteine levels are described for all baseline participants.

Baseline blood homocysteine lab levels and dietary intake levels are reported.

Outcome measures

Measure	Current Smoker n=31 Participants Study participants with current smoker status	Past Smoker Participants with past smoker status	Never Smoker Participants with never smoker status
Correlation Between Baseline Blood Homocysteine Levels and Dietary Intake	9.6 micromoles/liter Standard Deviation 2.4	—	—

PRIMARY outcome

Timeframe: Baseline

Population: All participants at baseline. For the present analysis, as opposed to a comparison of treatment groups, folate and B12 levels are described for all baseline participants.

Baseline blood folate and B12 lab levels and dietary intake levels are reported.

Outcome measures

Measure	Current Smoker n=16 Participants Study participants with current smoker status	Past Smoker Participants with past smoker status	Never Smoker Participants with never smoker status
Correlation Between Baseline Blood Folate or B12 Levels and Dietary Intake Natural folate, mcg	198.8 micrograms Standard Deviation 73.3	—	—
Correlation Between Baseline Blood Folate or B12 Levels and Dietary Intake Total folate, mcg	531.3 micrograms Standard Deviation 386.5	—	—
Correlation Between Baseline Blood Folate or B12 Levels and Dietary Intake Dietary folate, mcg	765.7 micrograms Standard Deviation 637.7	—	—
Correlation Between Baseline Blood Folate or B12 Levels and Dietary Intake Synthetic folate, mcg	333.4 micrograms Standard Deviation 362.9	—	—
Correlation Between Baseline Blood Folate or B12 Levels and Dietary Intake Total B12, mcg	7.5 micrograms Standard Deviation 7.3	—	—

SECONDARY outcome

Timeframe: Baseline

Population: One deficit syndrome participant and one participant without deficit syndrome are missing RBC folate values. For the present analysis, as opposed to a comparison of treatment groups, folate levels are compared across deficit syndrome status.

Baseline blood folate lab levels are reported by deficit syndrome status.

Outcome measures

Measure	Current Smoker n=17 Participants Study participants with current smoker status	Past Smoker n=14 Participants Participants with past smoker status	Never Smoker Participants with never smoker status
Correlations Between Baseline Blood Folate and Clinical Ratings of Negative Symptoms by Comparing Lab Levels in Deficit Syndrome Versus Non-deficit Syndrome Patients Serum folate, ng/ml	14.9 nanograms/mL Standard Deviation 4.3	14.0 nanograms/mL Standard Deviation 3.5	—
Correlations Between Baseline Blood Folate and Clinical Ratings of Negative Symptoms by Comparing Lab Levels in Deficit Syndrome Versus Non-deficit Syndrome Patients RBC folate, ng/ml	585 nanograms/mL Standard Deviation 171	546 nanograms/mL Standard Deviation 123	—

SECONDARY outcome

Timeframe: Baseline

Population: For the present analysis, as opposed to a comparison of treatment groups, B12 levels are compared across deficit syndrome status.

Baseline blood B12 lab levels are reported by deficit syndrome status.

Outcome measures

Measure	Current Smoker n=17 Participants Study participants with current smoker status	Past Smoker n=14 Participants Participants with past smoker status	Never Smoker Participants with never smoker status
Correlations Between Baseline Blood B12 Levels and Clinical Ratings of Negative Symptoms by Comparing Lab Levels in Deficit Syndrome Versus Non-deficit Syndrome Patients	603 picograms/mL Standard Deviation 193	513 picograms/mL Standard Deviation 275	—

SECONDARY outcome

Timeframe: Baseline

Population: One participant without deficit syndrome is missing homocysteine. For the present analysis, as opposed to a comparison of treatment groups, homocysteine levels are compared across deficit syndrome status.

Baseline blood homocysteine lab levels are reported by deficit syndrome status.

Outcome measures

Measure	Current Smoker n=17 Participants Study participants with current smoker status	Past Smoker n=13 Participants Participants with past smoker status	Never Smoker Participants with never smoker status
Correlations Between Baseline Blood Homocysteine Levels and Clinical Ratings of Negative Symptoms by Comparing Lab Levels in Deficit Syndrome Versus Non-deficit Syndrome Patients	9.4 micromoles/liter Standard Deviation 2.6	9.7 micromoles/liter Standard Deviation 2.5	—

Adverse Events

Folate

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Michelle Hill

Schizophrenia Program, Massachusetts General Hospital

Phone: 617-912-7846

Email: michelehill1@gmail.com

Results disclosure agreements

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