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| ID | Type | Description | Link |
|---|---|---|---|
| R01MH070831 | U.S. NIH Grant/Contract | View source | |
| DATR A5-ETPD |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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This study will evaluate the effectiveness of folate and B12 supplementation in reducing negative symptoms in people with schizophrenia.
About 30% of people with schizophrenia suffer from treatment-resistant psychotic symptoms, which may include social withdrawal, apathy, and depression. These negative symptoms can produce substantial distress for those affected, often disrupting social and occupational functioning and resulting in hospitalization. Although atypical antipsychotic medications have demonstrated some success in treating negative symptoms, the degree to which many negative symptoms respond is unclear. Depression and poor response to antidepressant medication have been linked to deficiency in the vitamins folate and B12. It is believed that vitamin supplementation with folate and B12 may offer a safe and inexpensive approach to improve outcomes for people with schizophrenia who have residual negative symptoms and have exhibited poor treatment response. This study will compare the effectiveness of folate and B12 versus placebo in reducing negative symptoms in people with schizophrenia.
Participation in this double-blind study will last 19 weeks. Potential participants will undergo initial screening, which will include a medical and psychiatric evaluation, physical exam, blood draw, urine sampling, and questionnaires. Participants will also be asked for permission to use a portion of the blood sample for genetic analysis. Eligible participants will be randomly assigned to take folate with B12 or placebo. Participants will first complete a 2-week stabilization phase, followed by the 16-week treatment study. Medication visits, occurring every 2 weeks during treatment, will include questions about medication side effects and the distribution of study medication. During specified medication visits, participants will complete various assessments, which will include questionnaires about schizophrenia, tests of learning and memory, repeat blood tests, and pregnancy tests. The medication visits will last between 15 minutes and 4 hours, depending on the scheduled assessments for that visit.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Folate with B12 | Active Comparator | Participants will take folic acid plus B12 for 18 weeks. |
|
| Placebo | Placebo Comparator | Participants will take placebo for 18 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Folic Acid | Dietary Supplement | Folic acid 2mg po daily |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Positive and Negative Syndrome Scale (PANSS) | 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. | Baseline vs. Week 16 |
| Measure | Description | Time Frame |
|---|---|---|
| Cognitive Deficits, as Measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Cognitive Battery Composite Score | Measured at Week 16 | |
| Positive Sub Scale of the Positive and Negative Syndrome Scale (PANSS) | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Donald Goff, MD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital Schizophrenia Program - Freedom Trail Clinic | Boston | Massachusetts | 02114 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23467813 | Result | Roffman JL, Lamberti JS, Achtyes E, Macklin EA, Galendez GC, Raeke LH, Silverstein NJ, Smoller JW, Hill M, Goff DC. Randomized multicenter investigation of folate plus vitamin B12 supplementation in schizophrenia. JAMA Psychiatry. 2013 May;70(5):481-9. doi: 10.1001/jamapsychiatry.2013.900. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | Placebo | Participants will take placebo for 18 weeks. Placebo: 1 capsule po daily |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Placebo | Participants will take placebo for 18 weeks. Placebo: 1 capsule po daily |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Positive and Negative Syndrome Scale (PANSS) | 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. | 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. | Posted | Mean | 95% Confidence Interval | units on a scale | Baseline vs. Week 16 |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalization due to worsening psychosis | Psychiatric disorders |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Nervous system disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Joshua L. Roffman, MD | Massachusetts General Hospital | 617-724-1920 | jroffman@partners.org |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D005492 | Folic Acid |
| D014805 | Vitamin B 12 |
| ID | Term |
|---|---|
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| B12 |
| Dietary Supplement |
B12 400 micrograms po daily |
|
|
| Placebo | Other | 1 capsule po daily |
|
| Baseline vs. Week 16 |
| Scale for Assessment of Negative Symptoms (SANS) | 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. | Baseline vs. Week 16 |
| Positive and Negative Syndrome Scale (PANSS) and FOLH1, MTHRF, MTR, and COMT Genotype | 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. | Baseline vs. Week 16 |
| Relationship Between Response of Negative and Positive Symptoms and the Change in RBC Folate, Serum Folate, Serum B12, and Plasma Homocysteine Concentrations | Measured at Week 16 |
| Touchstone innovare |
| Grand Rapids |
| Michigan |
| 49503 |
| United States |
| URMC Severe Mental Disorders Program | Rochester | New York | 14623 | United States |
| Lost to Follow-up |
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| BG002 | Total | Total of all reporting groups |
| Years |
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| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
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| Secondary | Cognitive Deficits, as Measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Cognitive Battery Composite Score | Not Posted | Measured at Week 16 |
| Secondary | Positive Sub Scale of the Positive and Negative Syndrome Scale (PANSS) | 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. | 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. | Posted | Mean | 95% Confidence Interval | units on a scale | Baseline vs. Week 16 |
|
|
|
| Secondary | Scale for Assessment of Negative Symptoms (SANS) | 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. | 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. | Posted | Mean | 95% Confidence Interval | units on a scale | Baseline vs. Week 16 |
|
|
|
| Secondary | Positive and Negative Syndrome Scale (PANSS) and FOLH1, MTHRF, MTR, and COMT Genotype | 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. | 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). | Posted | Mean | 95% Confidence Interval | units on a scale | Baseline vs. Week 16 |
|
|
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| Secondary | Relationship Between Response of Negative and Positive Symptoms and the Change in RBC Folate, Serum Folate, Serum B12, and Plasma Homocysteine Concentrations | Not Posted | Measured at Week 16 |
| 4 |
| 94 |
| 21 |
| 94 |
| EG001 | Placebo | Participants will take placebo for 18 weeks. Placebo: 1 capsule po daily | 4 | 46 | 16 | 46 |
| Cholelithiasis | Gastrointestinal disorders | Systematic Assessment |
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| Body Numbness | Nervous system disorders | Systematic Assessment |
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| Suicidal Tendency | Psychiatric disorders | Systematic Assessment |
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| Vision Decreased | Eye disorders | Systematic Assessment |
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| Brain Tumor | Nervous system disorders | Systematic Assessment |
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| Irritation of Skin | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Tachycardia | Cardiac disorders | Systematic Assessment |
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| Hypoglycemia | Endocrine disorders | Systematic Assessment |
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| Cholelithiasis | Gastrointestinal disorders | Systematic Assessment |
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| Dirrhea | Gastrointestinal disorders | Systematic Assessment |
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| Dry Mouth | Gastrointestinal disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Enuresis | Renal and urinary disorders | Systematic Assessment |
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| Numbness | Nervous system disorders | Systematic Assessment |
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| Delusions | Psychiatric disorders | Systematic Assessment |
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| Dizziness | Nervous system disorders | Systematic Assessment |
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| Injury | Nervous system disorders | Systematic Assessment |
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| Insomnia | Nervous system disorders | Systematic Assessment |
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| Manic Psychosis | Psychiatric disorders | Systematic Assessment |
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| Muscle Spasm | Nervous system disorders | Systematic Assessment |
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| Psychosis | Psychiatric disorders | Systematic Assessment |
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| Somnolence | Nervous system disorders | Systematic Assessment |
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| Suicidal Tendency | Psychiatric disorders | Systematic Assessment |
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| Back Pain | General disorders | Systematic Assessment |
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| Chest Pain | General disorders | Systematic Assessment |
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| Malaise | General disorders | Systematic Assessment |
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| Eye Blood Shot | Eye disorders | Systematic Assessment |
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| Vision Decreased | Eye disorders | Systematic Assessment |
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| Asthema | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Brain Tumor | Nervous system disorders | Systematic Assessment |
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| Infection | Infections and infestations | Systematic Assessment |
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| Laboratory Test Abnormality | General disorders | Systematic Assessment |
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| Irritation of Skin | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
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| D006571 | Heterocyclic Compounds |
| D045728 | Corrinoids |
| D045725 | Tetrapyrroles |
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |