Major Depressive DisorderPhase 4NCT00321152
A Study of 6(S)-5-MTHF Among Serotonin Reuptake Inhibitor(SSRI)-Resistant Outpatients With Major Depressive Disorder (MDD)
A Phase 4 study testing 6(S)-5-MTHF (a Medical Food) in people with Major Depressive Disorder, run by Massachusetts General Hospital at 11 sites in United States.
Trial summary
The purpose of the study is to test whether oral 6(S)-5-MTHF (Deplin®) is safe and effective in relieving depression when it is added to standard kinds of antidepressants called serotonin reuptake inhibitors (SSRIs). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- 6(S)-5-MTHF (a Medical Food)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 11 sitesUnited States
- Study dates
- Nov 2006to Jun 2010
- Phase
- Phase 4
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18-65 years old
- Meet criteria for current Major Depressive Disorder
- Currently taking an SSRI
Who cannot join
- Pregnant women
- Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease.
- Prior course of MTHF augmentation, or intolerance to MTHF at any dose
- substance use disorders active within the last six months, any bipolar disorder (current or past), or any psychotic disorder (current or past).
- Have failed more than 2 adequate antidepressant trials during the current Major Depressive Episode.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Burlington Medical Associates
Burlington, Massachusetts, 01803
Southeast Health Consultants, LLC
Charleston, South Carolina, 29407
Rush University Medical Center, Psychiatric Medicine Associates, LLC
Chicago, Illinois, 60612
Univeristy of Cincinnati, College of Medicine
Cincinnati, Ohio, 45267
Vanderbilt University Medical Center
Nashville, Tennessee, 37212
Lousiana State University Health Sciences Center
New Orleans, Louisiana, 70115
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of California San Diego School of Medicine
San Diego, California, 92161
Waltham Family Practice
Waltham, Massachusetts, 02453
Charles River Medical Associates
Westborough, Massachusetts, 01581
About this study
Official title: A Double-Blind, Placebo Controlled Study of 6(S)-5-MTHF Among SSRI-Resistant Outpatients With Major Depressive Disorder (MDD)
The purpose of the study is to test whether oral 6(S)-5-MTHF (Deplin®) is safe and effective in relieving depression when it is added to standard kinds of antidepressants called serotonin reuptake inhibitors (SSRIs).
Read the detailed description
The study consists of two sequential phases, each lasting a total of four weeks (8 weeks total), with visits every 10 days. Once patients agree to participate in the study by signing the informed consent document, a full medical and psychiatric history will be taken and a physical examination and blood draw will be performed. Screen rating scales will be performed. Screened and eligible patients will be asked to return two weeks later for a baseline visit when they will be randomized to double-blind treatment with placebo or Deplin (6(S)-5-MTHF). The double-blind treatment will last 60 days, during which patients will be seen every 10 days. Subjects will be randomized to one of three treatment groups: a)Deplin/Deplin, b) placebo/Deplin, c) placebo/placebo. Patients will have a greater than 50% chance of receiving active medication (Deplin) at some point in the 8 week study
- For patients randomly assigned to the Deplin/Deplin sequence, the dose of 6(S)-5-MTHF will be 7.5 mg/day during the first phase of the study, and 15 mg/d during the second phase of the study.
- For patients randomly assigned to the placebo/Deplin sequence, the dose of 6(S)-5-MTHF will be 7.5 mg/day during the second phase of the study.
- For patients randomly assigned to the placebo/placebo sequence, both tablets of study medication will be placebo during both phases of the study.
All patients will be asked to take two tablets of blinded study medication in the morning, in addition to their stable dose of ongoing SSRI treatment. Each study medication tablet will be either 7.5 mg of 6(S)-5-MTHF or matching placebo.
- Conditions
- Major Depressive Disorder
- Being tested
- 6(S)-5-MTHF (a Medical Food)
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
6(S)-5-MTHF (a Medical Food)Other
The study consists of 8 visits over a period of 8 weeks or 60 days. Eligible participants will be randomized to double-blind treatment with placebo or Deplin (6(S)-5-MTHF). Participants will have a greater than 50% chance of receiving active medication (Deplin) at some point in the 8 week study. At the end of the double-blind phase, both responders and non-responders who have completed the 8 week study will have the option of receiving free, open-label adjunctive treatment with either 7.5 mg or 15 mg of 6(S)-5-MTHF for 12 months. Subjects who agree to receive open-label treatment with 6(S)-5-MTHF for 12 months will be assessed every three (3) months until the end of the follow-up phase.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Deplin/Deplin = participants will receive 7.5 mg/day of Deplin (6(S)-5-MTHF)for the first 4 weeks, and then 15 mg/day of Deplin for the next 4 weeks. Receives: Other: 6(S)-5-MTHF (a Medical Food) |
| 2 | Experimental | placebo/Deplin = participants will receive placebo for the first 4 weeks, and then 7.5 mg/day of Deplin (6(S)-5-MTHF) for the next 4 weeks. Receives: Other: 6(S)-5-MTHF (a Medical Food) |
| 3 | Placebo comparator | placebo/placebo = both tablets of study medication will be placebo during both phases of the study. Receives: Other: 6(S)-5-MTHF (a Medical Food) |
What is being measured
The primary outcome is the main question the study is designed to answer.
HAM-D
Measured: every visit
Secondary outcomes (1)
QIDS-SR
Measured: every visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2006 (estimated)
- Study startNov 2006
- Primary completionAug 2008
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Pamlab, L.L.C.
- Investigators
- George I Papakostas, M.D, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00321152
- Sponsor's protocol ID
- 2006P000604
- Status last verified
- Jun 2010
- First submitted
- 1 May 2006
- Last updated
- 8 Jun 2010
- Results posted
- No
- Data monitoring committee
- No
Publications
Zajecka JM, Fava M, Shelton RC, Barrentine LW, Young P, Papakostas GI. Long-term efficacy, safety, and tolerability of L-methylfolate calcium 15 mg as adjunctive therapy with selective serotonin reuptake inhibitors: a 12-month, open-label study following a placebo-controlled acute study. J Clin Psychiatry. 2016 May;77(5):654-60. doi: 10.4088/JCP.15m10181.
PubMed 27035404Papakostas GI, Shelton RC, Zajecka JM, Etemad B, Rickels K, Clain A, Baer L, Dalton ED, Sacco GR, Schoenfeld D, Pencina M, Meisner A, Bottiglieri T, Nelson E, Mischoulon D, Alpert JE, Barbee JG, Zisook S, Fava M. L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials. Am J Psychiatry. 2012 Dec;169(12):1267-74. doi: 10.1176/appi.ajp.2012.11071114.
PubMed 23212058
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Placebo Controlled Study of 6(S)-5-MTHF Among SSRI-Resistant Outpatients With Major Depressive Disorder (MDD)
- ClinicalTrials.gov ID
- NCT00321152
- Acronym / sponsor ID
- 2006P000604
- Conditions
- Major Depressive Disorder
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Pamlab, L.L.C.
- Study start
- Nov 2006
- Primary completion
- Aug 2008 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 3 May 2006 (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.
The purpose of the study is to test whether oral 6(S)-5-MTHF (Deplin®) is safe and effective in relieving depression when it is added to standard kinds of antidepressants called serotonin reuptake inhibitors (SSRIs).
Detailed description
The study consists of two sequential phases, each lasting a total of four weeks (8 weeks total), with visits every 10 days. Once patients agree to participate in the study by signing the informed consent document, a full medical and psychiatric history will be taken and a physical examination and blood draw will be performed. Screen rating scales will be performed. Screened and eligible patients will be asked to return two weeks later for a baseline visit when they will be randomized to double-blind treatment with placebo or Deplin (6(S)-5-MTHF). The double-blind treatment will last 60 days, during which patients will be seen every 10 days. Subjects will be randomized to one of three treatment groups: a)Deplin/Deplin, b) placebo/Deplin, c) placebo/placebo. Patients will have a greater than 50% chance of receiving active medication (Deplin) at some point in the 8 week study
- For patients randomly assigned to the Deplin/Deplin sequence, the dose of 6(S)-5-MTHF will be 7.5 mg/day during the first phase of the study, and 15 mg/d during the second phase of the study.
- For patients randomly assigned to the placebo/Deplin sequence, the dose of 6(S)-5-MTHF will be 7.5 mg/day during the second phase of the study.
- For patients randomly assigned to the placebo/placebo sequence, both tablets of study medication will be placebo during both phases of the study.
All patients will be asked to take two tablets of blinded study medication in the morning, in addition to their stable dose of ongoing SSRI treatment. Each study medication tablet will be either 7.5 mg of 6(S)-5-MTHF or matching placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Other: 6(S)-5-MTHF (a Medical Food)Deplin/Deplin = participants will receive 7.5 mg/day of Deplin (6(S)-5-MTHF)for the first 4 weeks, and then 15 mg/day of Deplin for the next 4 weeks. |
| 2 | Experimental | Other: 6(S)-5-MTHF (a Medical Food)placebo/Deplin = participants will receive placebo for the first 4 weeks, and then 7.5 mg/day of Deplin (6(S)-5-MTHF) for the next 4 weeks. |
| 3 | Placebo comparator | Other: 6(S)-5-MTHF (a Medical Food)placebo/placebo = both tablets of study medication will be placebo during both phases of the study. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 18-65 years old
- Meet criteria for current Major Depressive Disorder
- Currently taking an SSRI
Key exclusion criteria (5 listed)
- Pregnant women
- Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease.
- Prior course of MTHF augmentation, or intolerance to MTHF at any dose
- substance use disorders active within the last six months, any bipolar disorder (current or past), or any psychotic disorder (current or past).
- Have failed more than 2 adequate antidepressant trials during the current Major Depressive Episode.
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 |
|---|---|---|
| 6(S)-5-MTHF (a Medical Food)The study consists of 8 visits over a period of 8 weeks or 60 days. Eligible participants will be randomized to double-blind treatment with placebo or Deplin (6(S)-5-MTHF). Participants will have a greater than 50% chance of receiving active medication (Deplin) at some point in the 8 week study. At the end of the double-blind phase, both responders and non-responders who have completed the 8 week study will have the option of receiving free, open-label adjunctive treatment with either 7.5 mg or 15 mg of 6(S)-5-MTHF for 12 months. Subjects who agree to receive open-label treatment with 6(S)-5-MTHF for 12 months will be assessed every three (3) months until the end of the follow-up phase. | Other | 1, 2, 3 |
Primary outcome
HAM-D
Time frame: every visit
1 secondary outcome
QIDS-SR
Time frame: every visit
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 8 Jun 2010.
- Derived from this study: PubMed 27035404Zajecka JM, Fava M, Shelton RC, Barrentine LW, Young P, Papakostas GI. Long-term efficacy, safety, and tolerability of L-methylfolate calcium 15 mg as adjunctive therapy with selective serotonin reuptake inhibitors: a 12-month, open-label study following a placebo-controlled acute study. J Clin Psychiatry. 2016 May;77(5):654-60. doi: 10.4088/JCP.15m10181.
- Derived from this study: PubMed 23212058Papakostas GI, Shelton RC, Zajecka JM, Etemad B, Rickels K, Clain A, Baer L, Dalton ED, Sacco GR, Schoenfeld D, Pencina M, Meisner A, Bottiglieri T, Nelson E, Mischoulon D, Alpert JE, Barbee JG, Zisook S, Fava M. L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials. Am J Psychiatry. 2012 Dec;169(12):1267-74. doi: 10.1176/appi.ajp.2012.11071114.
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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.
George I Papakostas, M.D principal investigator
Massachusetts General Hospital
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing 6(S)-5-MTHF (a Medical Food) in people with Major Depressive Disorder, run by Massachusetts General Hospital at 11 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 3 inclusion and 5 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 8 Jun 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 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?
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?
HAM-D (time frame: every visit). 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 NCT00321152, which also lists 2 linked publications.
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 8 Jun 2010.