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SchizophreniaPhase 4NCT00611806

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

A Phase 4 study testing Folic Acid and B12 in people with Schizophrenia, run by Massachusetts General Hospital at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 18 to 68 years
Conditions the study is for
Schizophrenia
What is being tested?
Folic Acid and B12
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
140 participants
Where
3 sitesUnited States
Study dates
Dec 2007to Dec 2010
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 68 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
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  • Positive baseline urine toxic screen
  • Unstable medical illness
  • Unstable psychiatric illness
  • Seizure disorder
  • Pregnant or breastfeeding

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Massachusetts General Hospital Schizophrenia Program - Freedom Trail Clinic

    Boston, Massachusetts, 02114

  • Touchstone innovare

    Grand Rapids, Michigan, 49503

  • URMC Severe Mental Disorders Program

    Rochester, New York, 14623

Other trials in United States

About this study

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

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

Read the 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
Being tested
Folic Acid, B12, Placebo
Keywords
Cognition, Folic Acid, B12
Medical subject headings
Schizophrenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Folic AcidDietary supplement

    Folic acid 2mg po daily

  • B12Dietary supplement

    Also called cobalamin

    B12 400 micrograms po daily

  • PlaceboOther

    1 capsule po daily

Study groups in NCT00611806
Study groupRoleWhat they receive
Folate with B12Active comparatorParticipants will take folic acid plus B12 for 18 weeks.
Receives: Dietary Supplement: Folic Acid; Dietary Supplement: B12
PlaceboPlacebo comparatorParticipants will take placebo for 18 weeks.
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline vs. Week 16

Secondary outcomes (5)

  1. Cognitive Deficits, as Measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Cognitive Battery Composite Score

    Measured: Measured at Week 16

  2. 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.

    Measured: Baseline vs. Week 16

  3. 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.

    Measured: Baseline vs. Week 16

  4. 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.

    Measured: Baseline vs. Week 16

  5. Relationship Between Response of Negative and Positive Symptoms and the Change in RBC Folate, Serum Folate, Serum B12, and Plasma Homocysteine Concentrations

    Measured: Measured at Week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Feb 2008 (estimated)
  2. Study startDec 2007
  3. Primary completionAug 2010
  4. Study completionDec 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
140 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00611806
Sponsor's protocol ID
R01MH070831
Other IDs
R01MH070831, DATR A5-ETPD
Status last verified
Jul 2014
First submitted
7 Feb 2008
Last updated
19 Aug 2014
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 23467813

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Folic Acid and B12 in people with Schizophrenia, run by Massachusetts General Hospital at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Positive and Negative Syndrome Scale (PANSS) (time frame: Baseline vs. Week 16). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00611806, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2014.

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