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

NCT ID: NCT00611806

Last Updated: 2014-08-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-31
• Study Completion Date: 2010-12-31

Brief Summary

This study will evaluate the effectiveness of folate and B12 supplementation in reducing negative symptoms in people with schizophrenia.

Detailed Description

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.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Folate with B12

Participants will take folic acid plus B12 for 18 weeks.

Group Type: ACTIVE_COMPARATOR

Folic Acid

Intervention Type: DIETARY_SUPPLEMENT

Folic acid 2mg po daily

B12

Intervention Type: DIETARY_SUPPLEMENT

B12 400 micrograms po daily

Placebo

Participants will take placebo for 18 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

1 capsule po daily

Interventions

Folic Acid

Folic acid 2mg po daily

Intervention Type: DIETARY_SUPPLEMENT

B12

B12 400 micrograms po daily

Intervention Type: DIETARY_SUPPLEMENT

Placebo

1 capsule po daily

Intervention Type: OTHER

Other Intervention Names

cobalamin

Eligibility Criteria

Inclusion Criteria

• Diagnosis of schizophrenia, any subtype
• Treated with an antipsychotic medication for at least 6 months at a stable dose for at least 6 weeks before study entry
• PANSS total score of at least 60, with a score of at least 3 (moderate) on one negative symptom item or on one positive symptom item
• Simpson Angus Scale (SAS) for Extrapyramidal Syndrome (EPS) total score of 12 or less
• A score of 2 (mild) or less on all items of the Calgary Depression Scale (CDS)
• Speaks English adequately enough to complete cognitive testing

Exclusion Criteria

• Serum B12 concentration less than 300 ug/L
• Complete blood count results consistent with megaloblastic anemia
• Serum creatinine concentration greater than 1.4
• Current use of folate or B12 supplementation
• Current use of any of the following medications: phenobarbital, phenytoin, carbamazepine, valproic acid, fosphenytoin, primidone, or pyrimethamine
• Alcohol or other substance abuse within 3 months before study entry (nicotine allowed)
• Positive baseline urine toxic screen
• Unstable medical illness
• Unstable psychiatric illness
• Seizure disorder
• Pregnant or breastfeeding

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 68 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Donald C. Goff, MD

Director of the Schizophrenia Clinical and Research Program

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Donald Goff, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital Schizophrenia Program - Freedom Trail Clinic

Boston, Massachusetts, United States

Touchstone innovare

Grand Rapids, Michigan, United States

URMC Severe Mental Disorders Program

Rochester, New York, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 23467813 (View on PubMed)

Other Identifiers

R01MH070831

Identifier Type: NIH

Identifier Source: secondary_id

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DATR A5-ETPD

Identifier Type: -

Identifier Source: secondary_id

R01MH070831

Identifier Type: NIH

Identifier Source: org_study_id

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