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
  Purpose

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


Condition Intervention Phase
Schizophrenia
Dietary Supplement: Folic Acid
Dietary Supplement: B12
Other: Placebo
Phase 4

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
Official Title: A Placebo-Controlled Trial of Folate With B12 in Schizophrenia Patients With Residual Symptoms

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Baseline vs. Week 16 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Positive Sub Scale of the Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Baseline vs. Week 16 ] [ Designated as safety issue: No ]
    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.

  • Scale for Assessment of Negative Symptoms (SANS) [ Time Frame: Baseline vs. Week 16 ] [ Designated as safety issue: No ]
    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.

  • Positive and Negative Syndrome Scale (PANSS) and FOLH1, MTHRF, MTR, and COMT Genotype [ Time Frame: Baseline vs. Week 16 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]

Enrollment: 140
Study Start Date: December 2007
Study Completion Date: December 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Folate with B12
Participants will take folic acid plus B12 for 18 weeks.
Dietary Supplement: Folic Acid
Folic acid 2mg po daily
Dietary Supplement: B12
B12 400 micrograms po daily
Other Name: cobalamin
Placebo Comparator: Placebo
Participants will take placebo for 18 weeks.
Other: Placebo
1 capsule po daily

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.

  Eligibility

Ages Eligible for Study:   18 Years to 68 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00611806

Locations
United States, Massachusetts
Massachusetts General Hospital Schizophrenia Program - Freedom Trail Clinic
Boston, Massachusetts, United States, 02114
United States, Michigan
Touchstone innovare
Grand Rapids, Michigan, United States, 49503
United States, New York
URMC Severe Mental Disorders Program
Rochester, New York, United States, 14623
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Donald Goff, MD Massachusetts General Hospital
  More Information

Publications:
Responsible Party: Donald C. Goff, MD, Director of the Schizophrenia Clinical and Research Program, 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

Keywords provided by Massachusetts General Hospital:
Cognition
Folic Acid
B12

Additional relevant MeSH terms:
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Folic Acid
Vitamin B Complex
Growth Substances
Hematinics
Hematologic Agents
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Vitamins

ClinicalTrials.gov processed this record on October 30, 2014