SchizophreniaNCT01091506
A Placebo-Controlled Study of Physiologic Effects of L-methylfolate in Schizophrenia Patients
A study testing L-methylfolate in people with Schizophrenia, run by Pamlab, Inc. at 1 site in United States.
Trial summary
This study is a 12-week, double-blind, placebo-controlled trial of L-methylfolate 15 mg/d supplementation in schizophrenia patients with mild or greater negative symptoms. L-methylfolate, a prescription medical food, is the activated form of folate required for conversion of homocysteine to methionine and hence is the… Read more about this study
- Who is it for?
- Ages 18 to 68 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- L-methylfolate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2010to Jun 2014
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Male of female
- Age 18-68 years
- Treated with an antipsychotic for at least 6 months at a stable dose for at least 6 weeks
- PANSS total score of at least 60, with at least 3 (moderate) on one negative symptom item or on one positive symptom item
- Simpson Angus Scale (SAS) for the EPS total score of 12 or less and
- A score of 2 (mild) or less on all items of the Calgary Depression Rating Scale (CDRS)
- Comprehension of English adequate to complete cognitive testing
Who cannot join
- Unable to provide informed consent
- CBC results consistent with megaloblastic anemia
- Serum creatinine concentration greater than 1.4
- Current use of folate supplementation > 400mcg folate
- Alcohol or other substance abuse within 3 months (nicotine allowed)
- Current use of any of the following medications: phenobarbital, phenytoin, carbamazepine, valproic acid, fosphenytoin, primidone or pyrimethamine
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- Positive baseline urine toxic screen, (positive test for PCP, barbiturates, cannabinoids, amphetamines, benzodiazepines, opiates, or cocaine)
- Unstable medical illness (exclusionary lab values are listed in Appendix A)
- Unstable psychiatric illness
- Seizure disorder
- Pregnant or nursing, or planning/trying to get pregnant within the next 6 months, and
- DSM-IV diagnosis of major depressive disorder
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital (MGH) Schizophrenia Program at Freedom Trail Clinic
Boston, Massachusetts
About this study
This study is a 12-week, double-blind, placebo-controlled trial of L-methylfolate 15 mg/d supplementation in schizophrenia patients with mild or greater negative symptoms. L-methylfolate, a prescription medical food, is the activated form of folate required for conversion of homocysteine to methionine and hence is the optimal form of folate for supplementation, since it eliminates the need for activation by MTHFR. The purpose of this study is to examine the change in plasma L-methylfolate concentrations following a three-month trial of L-methylfolate 15 mg/d compared to placebo.
Read the detailed description
Blood levels of L-methylfolate and biological activity will be evaluated by examining changes in plasma homocysteine concentrations, serum methionine concentrations and changes in brain activation as measured by fMRI.
- Conditions
- Schizophrenia
- Being tested
- Placebo, L-methylfolate
- Keywords
- L-methylfolate, Deplin, schizophrenia, folate, folic acid, homocysteine, methionine, MTHFR genotype, C677T mutation, vitamin B6, vitamin B12, psychotic symptoms, MTHFR C677T Polymorphism
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboOther
Placebo once a day for 12 weeks
L-methylfolateOther
Also called Deplin
L-methylfolate 15mg once a day for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| L-methylfolate | Experimental | L-methylfolate 15mg (a medical food) Receives: Other: L-methylfolate |
| Placebo | Placebo comparator | Placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Examine the change in plasma L-methylfolate concentrations following a three-month trial of L-methylfolate 15 mg/d compared to placebo.
Measured: Weeks 2, 8, and 12
Secondary outcomes (9)
Examine the change in brain activation in patients receiving L-methylfolate 15 mg/d versus placebo as measured by fMRI using Sternberg's Iterm Recognition Paradigm, as well as changes in cortical thickness and connectivity.
Measured: Week 12
Examine the relationship between MTHFR genotype, change in plasma homocysteine, and methionine concentration, and change in DLPC activation in subjects receiving L-methylfolate
Measured: Weeks 2, 8, and 12
Examine the change in negative symptoms (SANS total score) after three months compared to placebo
Measured: Weeks 2, 8, and 12
Examine the change in negative symptoms (SANS total score) in relation to change in plasma L-methylfolate levels
Measured: Weeks 2, 8, and 12
Examine the change in MATRICS cognitive battery composite score after three months compared to placebo
Measured: Weeks 2, 8, and 12
Examine the change in MATRICS cognitive battery composite score after three months in relation to change in plasma L-methylfolate concentration.
Measured: Weeks 2, 8, and 12
Examine the change in psychotic symptoms as measured by the PANSS total and subscale scores after three months compared to placebo
Measured: Weeks 2, 8, and 12
Examine the change in psychotic symptoms (PANSS score) in relation to change in plasma L-methylfolate concentration.
Measured: Weeks 2, 8, and 12
Examine the change in plasma homocysteine and methionine concentrations following a three-month trial of L-methylfolate 15 mg/d compared to placebo.
Measured: Weeks 2, 8, and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2010 (estimated)
- Study startMar 2010
- Primary completionMar 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pamlab, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Massachusetts General Hospital
- Responsible party
- Sponsor
- Investigators
- Joshua Roffman, MD, Principal investigator, Massachusetts General Hospital Schizophrenia Program at Freedom Trail Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01091506
- Sponsor's protocol ID
- D-003
- Status last verified
- Jan 2015
- First submitted
- 22 Mar 2010
- Last updated
- 3 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Roffman JL, Petruzzi LJ, Tanner AS, Brown HE, Eryilmaz H, Ho NF, Giegold M, Silverstein NJ, Bottiglieri T, Manoach DS, Smoller JW, Henderson DC, Goff DC. Biochemical, physiological and clinical effects of l-methylfolate in schizophrenia: a randomized controlled trial. Mol Psychiatry. 2018 Feb;23(2):316-322. doi: 10.1038/mp.2017.41. Epub 2017 Mar 14.
PubMed 28289280
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Placebo-Controlled Study of Physiologic Effects of L-methylfolate in Schizophrenia Patients
- ClinicalTrials.gov ID
- NCT01091506
- Acronym / sponsor ID
- D-003
- Conditions
- Schizophrenia
- Keywords
- L-methylfolate, Deplin, schizophrenia, folate, folic acid, homocysteine, methionine, MTHFR genotype
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Pamlab, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Massachusetts General Hospital
- Study start
- Mar 2010
- Primary completion
- Mar 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 24 Mar 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a 12-week, double-blind, placebo-controlled trial of L-methylfolate 15 mg/d supplementation in schizophrenia patients with mild or greater negative symptoms. L-methylfolate, a prescription medical food, is the activated form of folate required for conversion of homocysteine to methionine and hence is the optimal form of folate for supplementation, since it eliminates the need for activation by MTHFR. The purpose of this study is to examine the change in plasma L-methylfolate concentrations following a three-month trial of L-methylfolate 15 mg/d compared to placebo.
Detailed description
Blood levels of L-methylfolate and biological activity will be evaluated by examining changes in plasma homocysteine concentrations, serum methionine concentrations and changes in brain activation as measured by fMRI.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| L-methylfolate | Experimental | Other: L-methylfolateL-methylfolate 15mg (a medical food) |
| Placebo | Placebo comparator | Other: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 68 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Diagnosis of schizophrenia, any subtype
- Male of female
- Age 18-68 years
- Treated with an antipsychotic for at least 6 months at a stable dose for at least 6 weeks
- PANSS total score of at least 60, with at least 3 (moderate) on one negative symptom item or on one positive symptom item
Key exclusion criteria (12 listed)
- Unable to provide informed consent
- CBC results consistent with megaloblastic anemia
- Serum creatinine concentration greater than 1.4
- Current use of folate supplementation > 400mcg folate
- Alcohol or other substance abuse within 3 months (nicotine allowed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboPlacebo once a day for 12 weeks | Other | Placebo |
| L-methylfolateAlso: DeplinL-methylfolate 15mg once a day for 12 weeks | Other | L-methylfolate |
Primary outcome
Examine the change in plasma L-methylfolate concentrations following a three-month trial of L-methylfolate 15 mg/d compared to placebo.
Time frame: Weeks 2, 8, and 12
9 secondary outcomes
Examine the change in brain activation in patients receiving L-methylfolate 15 mg/d versus placebo as measured by fMRI using Sternberg's Iterm Recognition Paradigm, as well as changes in cortical thickness and connectivity.
Time frame: Week 12
Examine the relationship between MTHFR genotype, change in plasma homocysteine, and methionine concentration, and change in DLPC activation in subjects receiving L-methylfolate
Time frame: Weeks 2, 8, and 12
Examine the change in negative symptoms (SANS total score) after three months compared to placebo
Time frame: Weeks 2, 8, and 12
Examine the change in negative symptoms (SANS total score) in relation to change in plasma L-methylfolate levels
Time frame: Weeks 2, 8, and 12
Examine the change in MATRICS cognitive battery composite score after three months compared to placebo
Time frame: Weeks 2, 8, and 12
Examine the change in MATRICS cognitive battery composite score after three months in relation to change in plasma L-methylfolate concentration.
Time frame: Weeks 2, 8, and 12
Examine the change in psychotic symptoms as measured by the PANSS total and subscale scores after three months compared to placebo
Time frame: Weeks 2, 8, and 12
Examine the change in psychotic symptoms (PANSS score) in relation to change in plasma L-methylfolate concentration.
Time frame: Weeks 2, 8, and 12
Examine the change in plasma homocysteine and methionine concentrations following a three-month trial of L-methylfolate 15 mg/d compared to placebo.
Time frame: Weeks 2, 8, and 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2016.
- Derived from this study: PubMed 28289280Roffman JL, Petruzzi LJ, Tanner AS, Brown HE, Eryilmaz H, Ho NF, Giegold M, Silverstein NJ, Bottiglieri T, Manoach DS, Smoller JW, Henderson DC, Goff DC. Biochemical, physiological and clinical effects of l-methylfolate in schizophrenia: a randomized controlled trial. Mol Psychiatry. 2018 Feb;23(2):316-322. doi: 10.1038/mp.2017.41. Epub 2017 Mar 14.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joshua Roffman, MD principal investigator
Massachusetts General Hospital Schizophrenia Program at Freedom Trail Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing L-methylfolate in people with Schizophrenia, run by Pamlab, Inc. at 1 site 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 8 inclusion and 12 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 3 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Examine the change in plasma L-methylfolate concentrations following a three-month trial of L-methylfolate 15 mg/d compared to placebo. (time frame: Weeks 2, 8, and 12). 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 NCT01091506, 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 3 Aug 2016.