Effectiveness of Vitamin Supplementation in Treating People With Residual Symptoms of Schizophrenia

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Donald C. Goff, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00611806
First received: February 7, 2008
Last updated: July 31, 2014
Last verified: July 2014
Results First Received: July 31, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Schizophrenia
Interventions: Dietary Supplement: Folic Acid
Dietary Supplement: B12
Other: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
189 Participants were screened for enrollment, but 49 were excluded. 40 were ineligible, 2 withdrew consent, 1 terminated because of an adverse event, and 6 were terminated because of study visit noncompliance.

Reporting Groups
  Description
Folate With B12

Participants will take folic acid plus B12 for 18 weeks.

Folic Acid: Folic acid 2mg po daily

B12: B12 400 micrograms po daily

Placebo

Participants will take placebo for 18 weeks.

Placebo: 1 capsule po daily


Participant Flow:   Overall Study
    Folate With B12     Placebo  
STARTED     94     46  
COMPLETED     78     43  
NOT COMPLETED     16     3  
Withdrawal by Subject                 8                 2  
Adverse Event                 2                 1  
Lost to Follow-up                 6                 0  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Folate With B12

Participants will take folic acid plus B12 for 18 weeks.

Folic Acid: Folic acid 2mg po daily

B12: B12 400 micrograms po daily

Placebo

Participants will take placebo for 18 weeks.

Placebo: 1 capsule po daily

Total Total of all reporting groups

Baseline Measures
    Folate With B12     Placebo     Total  
Number of Participants  
[units: participants]
  94     46     140  
Age  
[units: Years]
Mean ± Standard Deviation
  45.3  ± 1.1     45.9  ± 1.6     45.6  ± 1.35  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     94     46     140  
>=65 years     0     0     0  
Gender  
[units: participants]
     
Female     28     32     60  
Male     66     14     80  
Region of Enrollment  
[units: participants]
     
United States     94     46     140  



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Positive and Negative Syndrome Scale (PANSS)   [ Time Frame: Baseline vs. Week 16 ]

Measure Type Primary
Measure Title Positive and Negative Syndrome Scale (PANSS)
Measure Description The change from baseline on the Positive and Negative Syndrome Scale (PANSS).The PANNS has three subscales: positive (score range 7-49), negative (score range 7-49), and general psychopathology (score range 16-112). The PANSS positive symptom sub-scale is comprised of 7 items rated on a scale of 1-7, representing positive symptoms of schizophrenia. The PANSS negative symptom subscale is comprised of 7 items rated on a scale of 1-7 representing the negative symptoms of schizophrenia, and the general psychopathology subscale is comprised of 16 items rated on a scale of 1-7 representing symptoms of general psychopathology in mental illness. The total score was computed by adding all the items on the sub-scale together. Scores reported are change in symptoms per week, relative to baseline. A negative score represents a decrease in total PANSS score per week, whereas a positive score represents an increase in total PANSS score per week.
Time Frame Baseline vs. Week 16  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants analyzed were those who completed at least 1 post-baseline visit or more (n = 135). 120 participants completed the study to the week 16 endpoint; however, 15 participants did not complete the entire 16 weeks, but completed at least one post-baseline study visit where the PANSS assessment was performed.

Reporting Groups
  Description
Folate With B12

Participants will take folic acid plus B12 for 18 weeks.

Folic Acid: Folic acid 2mg po daily

B12: B12 400 micrograms po daily

Placebo

Participants will take placebo for 18 weeks.

Placebo: 1 capsule po daily


Measured Values
    Folate With B12     Placebo  
Number of Participants Analyzed  
[units: participants]
  89     46  
Positive and Negative Syndrome Scale (PANSS)  
[units: units on a scale]
Mean ( 95% Confidence Interval )
  -.21  
  ( -.35 to -.07 )  
  -.22  
  ( -.42 to -.03 )  

No statistical analysis provided for Positive and Negative Syndrome Scale (PANSS)



2.  Secondary:   Positive Sub Scale of the Positive and Negative Syndrome Scale (PANSS)   [ Time Frame: Baseline vs. Week 16 ]

Measure Type Secondary
Measure Title Positive Sub Scale of the Positive and Negative Syndrome Scale (PANSS)
Measure Description The change from baseline on the positive symptom sub-scale of the Positive and Negative Syndrome Scale (PANSS). Total PANSS positive symptom sub-scale scores range from 7-49. The PANSS positive symptom sub-scale is comprised of 7 items rated on a scale of 1-7: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. A score of one on each item 1 absent, 2 is minimal, 3 is mild, 4 is moderate, 5 is moderately severe, 6 is severe, and 7 is extreme. The total score was computed by adding all the items on the sub-scale together. Scores reported are change in symptoms per week, relative to baseline. A negative score represents a decrease in total PANSS score per week, whereas a positive score represents an increase in total PANSS score per week.
Time Frame Baseline vs. Week 16  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants analyzed were those who completed at least 1 post-baseline visit or more (n = 135). 120 participants completed the study to the week 16 endpoint; however, 15 participants did not complete the entire 16 weeks, but completed at least one post-baseline study visit where the PANSS assessment was performed.

Reporting Groups
  Description
Folate With B12

Participants will take folic acid plus B12 for 18 weeks.

Folic Acid: Folic acid 2mg po daily

B12: B12 400 micrograms po daily

Placebo

Participants will take placebo for 18 weeks.

Placebo: 1 capsule po daily


Measured Values
    Folate With B12     Placebo  
Number of Participants Analyzed  
[units: participants]
  89     46  
Positive Sub Scale of the Positive and Negative Syndrome Scale (PANSS)  
[units: units on a scale]
Mean ( 95% Confidence Interval )
  -.06  
  ( -.12 to -.01 )  
  -.04  
  ( -.11 to .03 )  

No statistical analysis provided for Positive Sub Scale of the Positive and Negative Syndrome Scale (PANSS)



3.  Secondary:   Scale for Assessment of Negative Symptoms (SANS)   [ Time Frame: Baseline vs. Week 16 ]

Measure Type Secondary
Measure Title Scale for Assessment of Negative Symptoms (SANS)
Measure Description The change from baseline on the scale for the assessment of negative symptoms (SANS) total score. Total SANS scores range from 0-100. The SANS is comprised of 5 subscores: 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 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. Scores reported are change in symptoms per week, relative to baseline. A negative score represents a decrease in total SANS score per week, whereas a positive score represents an increase in total SANS score per week.
Time Frame Baseline vs. Week 16  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants analyzed were those who completed at least 1 post-baseline visit or more (n = 135). 120 participants completed the study to the week 16 endpoint; however, 15 participants did not complete the entire 16 weeks, but completed at least one post-baseline study visit where the SANS assessment was performed.

Reporting Groups
  Description
Folate With B12

Participants will take folic acid plus B12 for 18 weeks.

Folic Acid: Folic acid 2mg po daily

B12: B12 400 micrograms po daily

Placebo

Participants will take placebo for 18 weeks.

Placebo: 1 capsule po daily


Measured Values
    Folate With B12     Placebo  
Number of Participants Analyzed  
[units: participants]
  89     46  
Scale for Assessment of Negative Symptoms (SANS)  
[units: units on a scale]
Mean ( 95% Confidence Interval )
  -.19  
  ( -.35 to -.03 )  
  .02  
  ( -.21 to .24 )  

No statistical analysis provided for Scale for Assessment of Negative Symptoms (SANS)



4.  Secondary:   Positive and Negative Syndrome Scale (PANSS) and FOLH1, MTHRF, MTR, and COMT Genotype   [ Time Frame: Baseline vs. Week 16 ]

Measure Type Secondary
Measure Title Positive and Negative Syndrome Scale (PANSS) and FOLH1, MTHRF, MTR, and COMT Genotype
Measure Description The change from baseline on the Positive and Negative Syndrome Scale (PANSS) (including FOLH1, MTHRF, MTR, and COMT genotype simultaneously into a linear mixed model).The PANNS has three sub-scales: positive (score range 7-49), negative (score range 7-49), and general psychopathology (score range 16-112). The PANSS negative and positive symptom sub-scale is comprised of 7 items rated on a scale of 1-7 representing the negative and positive symptoms of schizophrenia, respectively, and the general psychopathology sub-scale is comprised of 16 items rated on a scale of 1-7 representing symptoms of general psychopathology in mental illness. The total score was computed by adding all the items on the sub-scale together. Scores reported are change in symptoms per week, relative to baseline. A negative score represents a decrease in total PANSS score per week, whereas a positive score represents an increase in total PANSS score per week.
Time Frame Baseline vs. Week 16  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants analyzed were those who completed at least 1 post-baseline visit or more (n = 135) and agreed to the DNA blood draw (n = 120).

Reporting Groups
  Description
Folate With B12

Participants will take folic acid plus B12 for 18 weeks.

Folic Acid: Folic acid 2mg po daily

B12: B12 400 micrograms po daily

Placebo

Participants will take placebo for 18 weeks.

Placebo: 1 capsule po daily


Measured Values
    Folate With B12     Placebo  
Number of Participants Analyzed  
[units: participants]
  79     41  
Positive and Negative Syndrome Scale (PANSS) and FOLH1, MTHRF, MTR, and COMT Genotype  
[units: units on a scale]
Mean ( 95% Confidence Interval )
  -.21  
  ( -.35 to -.07 )  
  -.1  
  ( -.31 to .11 )  

No statistical analysis provided for Positive and Negative Syndrome Scale (PANSS) and FOLH1, MTHRF, MTR, and COMT Genotype



5.  Secondary:   Cognitive Deficits, as Measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Cognitive Battery Composite Score   [ Time Frame: Measured at Week 16 ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

6.  Secondary:   Relationship Between Response of Negative and Positive Symptoms and the Change in RBC Folate, Serum Folate, Serum B12, and Plasma Homocysteine Concentrations   [ Time Frame: Measured at Week 16 ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Joshua L. Roffman, MD
Organization: Massachusetts General Hospital
phone: 617-724-1920
e-mail: jroffman@partners.org


Publications of Results:

Responsible Party: Donald C. Goff, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00611806     History of Changes
Other Study ID Numbers: R01 MH070831, R01MH070831, DATR A5-ETPD
Study First Received: February 7, 2008
Results First Received: July 31, 2014
Last Updated: July 31, 2014
Health Authority: United States: Federal Government