DepressionPhase 4TRD-2NCT00955955
Study of 6(S)-5-MTHF Among Selective Serotonin Reuptake Inhibitor-Resistant Outpatients With Major Depressive Disorder
A Phase 4 study testing 6(S)-5-MTHF(Deplin) in people with Depression, run by George I. Papakostas at 6 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
- Depression
- What is being tested?
- 6(S)-5-MTHF(Deplin)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 6 sitesUnited States
- Study dates
- Jul 2009to Apr 2011
- 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 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), any psychotic disorder (current or past)
- Have failed more than 2 adequate antidepressant trials during the current Major Depressive Episode
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Rush University Medical Center, Psychiatric Medicine Associates, LLC
Chicago, Illinois, 60612
University of Cincinnati, College of Medicine
Cincinnati, Ohio, 45221
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of California San Diego School of Medicine
San Diego, California, 92093
About this study
Official title: TRD - 2: 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 phases, each lasting a total of four weeks (8 weeks total), with visits at the DCRP every 10 days. If the subject is eligible, they will be asked to return two weeks later for a baseline visit, when they will be randomly assigned, like a flip of a coin, to one of three treatment groups: a) drug/drug, b) placebo/drug, c) placebo/placebo (a placebo is a pill that looks like a study drug but contains no active medication). They will have a greater than 50% chance of receiving active medication (Deplin) at some point in the 8 week study.
Neither the subject nor the research staff will know which group the subject is in.
All subjects will be asked to take the study medication in the morning, in addition to their ongoing SSRI treatment.
- Conditions
- Depression
- Being tested
- 6(S)-5-MTHF(Deplin), Placebo
- Keywords
- Depression, Medical food
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
6(S)-5-MTHF(Deplin)Other
Deplin is a medical food. Patients will take 15 mg/day of deplin.
PlaceboOther
Inactive substance
| Study group | Role | What they receive |
|---|---|---|
| 6(S)-5-MTHF(Deplin) | Experimental | Participants will receive 15 mg/day of Deplin, a medical food, for 8 weeks.
The SPCD approach, is modified and conducted as follows:
The phase II dataset of interest is limited to patients treated with placebo during phase I who completed phase I, who did not experience a clinical response according to the HDRS-17 during phase I and entered phase II. Drug is compared to placebo in phase II for this patient subset alone.
The ITT/LOCF data comparing drug and placebo during phase I is combined with the data comparing drug and placebo according to the SPCD model for phase II (see steps 2 and 3 above), and analyzed using the statistical model as described in Fava et al, 2003 Receives: Other: 6(S)-5-MTHF(Deplin) |
| Placebo/Deplin | Experimental | Participants will receive placebo for the first 4 weeks, and then 15 mg/day of Deplin (6(S)-5-MTHF) for the next 4 weeks.
The SPCD approach, is modified and conducted as follows:
The phase II dataset of interest is limited to patients treated with placebo during phase I who completed phase I, who did not experience a clinical response according to the HDRS-17 during phase I and entered phase II. Drug is compared to placebo in phase II for this patient subset alone.
The ITT/LOCF data comparing drug and placebo during phase I is combined with the data comparing drug and placebo according to the SPCD model for phase II (see steps 2 and 3 above), and analyzed using the statistical model as described in Fava et al, 2003 Receives: Other: 6(S)-5-MTHF(Deplin); Other: Placebo |
| Placebo/Placebo | Experimental | Participants will receive placebo for both phases of the study.
The SPCD approach, is modified and conducted as follows:
The phase II dataset of interest is limited to patients treated with placebo during phase I who completed phase I, who did not experience a clinical response according to the HDRS-17 during phase I and entered phase II. Drug is compared to placebo in phase II for this patient subset alone.
The ITT/LOCF data comparing drug and placebo during phase I is combined with the data comparing drug and placebo according to the SPCD model for phase II (see steps 2 and 3 above), and analyzed using the statistical model as described in Fava et al, 2003 Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The 17-item Hamilton Depression Scale (HAM-D-17)
The HAM-D-17 is a multiple choice questionnaire that clinicians may use to rate the severity of a patient's major depression. Items are scored on a scale of zero to four and higher scores indicate greater impairment. This scale is scored by summing the scores on each item and scores can range from 0-68.
When assessing changes in HAMD score, negative changes indicate improvement (i.e. the score has decreased) and positive scores indicate a worsening of symptoms (i.e. scores have increased).
Measured: Baseline and Day 60
Secondary outcomes (1)
The Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR)
This measure is a 16 item self report questionnaire assessing symptoms of depression. For each item, scores range from 0 to 3 with higher scores indicating greater impairment. To score this measure:
- Enter the highest score from questions 1-4 (sleep items): ______
- Enter score on item 5 ____
- Enter the highest score from questions 6-9 (appetite/weight): ______
- Enter score on item 10 ____
- Enter score on item 11 ____
- Enter score on item 12 ____
- Enter score on item 13 ____
- Enter score on item 14 ____
- Enter the highest score from questions 15-16 (psychomotor items): ______
Total score range 0-27: ______
When assessing changes in this measure over time, negative means indicate an improvement (i.e. the scores decreased over time) and positive means indicate worsening in functioning.
Measured: Baseline and Day 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2009 (estimated)
- Study startJul 2009
- Primary completionApr 2011
- Study completionApr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- George I. Papakostas
- Sponsor type
- University, hospital or other
- Collaborators
- Pamlab, L.L.C.
- Responsible party
- Sponsor-investigator, George I. Papakostas, Massachusetts General Hospital
- Investigators
- George I. Papakostas, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00955955
- Sponsor's protocol ID
- 2006P000604 (2)
- Acronym
- TRD-2
- Status last verified
- Mar 2017
- First submitted
- 30 Jul 2009
- Last updated
- 28 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Shelton RC, Pencina MJ, Barrentine LW, Ruiz JA, Fava M, Zajecka JM, Papakostas GI. Association of obesity and inflammatory marker levels on treatment outcome: results from a double-blind, randomized study of adjunctive L-methylfolate calcium in patients with MDD who are inadequate responders to SSRIs. J Clin Psychiatry. 2015 Dec;76(12):1635-41. doi: 10.4088/JCP.14m09587.
PubMed 26613389Papakostas GI, Shelton RC, Zajecka JM, Bottiglieri T, Roffman J, Cassiello C, Stahl SM, Fava M. Effect of adjunctive L-methylfolate 15 mg among inadequate responders to SSRIs in depressed patients who were stratified by biomarker levels and genotype: results from a randomized clinical trial. J Clin Psychiatry. 2014 Aug;75(8):855-63. doi: 10.4088/JCP.13m08947.
PubMed 24813065Papakostas 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 28 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TRD - 2: A Double-Blind, Placebo Controlled Study of 6(S)-5-MTHF Among SSRI-Resistant Outpatients With Major Depressive Disorder (MDD)
- ClinicalTrials.gov ID
- NCT00955955
- Acronym / sponsor ID
- TRD-2 / 2006P000604 (2)
- Conditions
- Depression
- Keywords
- Depression, Medical food
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- George I. PapakostasUniversity, hospital or other
- Collaborators
- Pamlab, L.L.C.
- Study start
- Jul 2009
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 10 Aug 2009 (estimated)
- Results
- Posted 18 Jan 2013
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 phases, each lasting a total of four weeks (8 weeks total), with visits at the DCRP every 10 days. If the subject is eligible, they will be asked to return two weeks later for a baseline visit, when they will be randomly assigned, like a flip of a coin, to one of three treatment groups: a) drug/drug, b) placebo/drug, c) placebo/placebo (a placebo is a pill that looks like a study drug but contains no active medication). They will have a greater than 50% chance of receiving active medication (Deplin) at some point in the 8 week study.
Neither the subject nor the research staff will know which group the subject is in.
All subjects will be asked to take the study medication in the morning, in addition to their ongoing SSRI treatment.
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 |
|---|---|---|
| 6(S)-5-MTHF(Deplin) | Experimental | Other: 6(S)-5-MTHF(Deplin)Participants will receive 15 mg/day of Deplin, a medical food, for 8 weeks. The SPCD approach, is modified and conducted as follows: The phase II dataset of interest is limited to patients treated with placebo during phase I who completed phase I, who did not experience a clinical response according to the HDRS-17 during phase I and entered phase II. Drug is compared to placebo in phase II for this patient subset alone. The ITT/LOCF data comparing drug and placebo during phase I is combined with the data comparing drug and placebo according to the SPCD model for phase II (see steps 2 and 3 above), and analyzed using the statistical model as described in Fava et al, 2003 |
| Placebo/Deplin | Experimental | Other: 6(S)-5-MTHF(Deplin), Other: PlaceboParticipants will receive placebo for the first 4 weeks, and then 15 mg/day of Deplin (6(S)-5-MTHF) for the next 4 weeks. The SPCD approach, is modified and conducted as follows: The phase II dataset of interest is limited to patients treated with placebo during phase I who completed phase I, who did not experience a clinical response according to the HDRS-17 during phase I and entered phase II. Drug is compared to placebo in phase II for this patient subset alone. The ITT/LOCF data comparing drug and placebo during phase I is combined with the data comparing drug and placebo according to the SPCD model for phase II (see steps 2 and 3 above), and analyzed using the statistical model as described in Fava et al, 2003 |
| Placebo/Placebo | Experimental | Other: PlaceboParticipants will receive placebo for both phases of the study. The SPCD approach, is modified and conducted as follows: The phase II dataset of interest is limited to patients treated with placebo during phase I who completed phase I, who did not experience a clinical response according to the HDRS-17 during phase I and entered phase II. Drug is compared to placebo in phase II for this patient subset alone. The ITT/LOCF data comparing drug and placebo during phase I is combined with the data comparing drug and placebo according to the SPCD model for phase II (see steps 2 and 3 above), and analyzed using the statistical model as described in Fava et al, 2003 |
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), 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(Deplin)Deplin is a medical food. Patients will take 15 mg/day of deplin. | Other | 6(S)-5-MTHF(Deplin), Placebo/Deplin |
| PlaceboInactive substance | Other | Placebo/Deplin, Placebo/Placebo |
Primary outcome
The 17-item Hamilton Depression Scale (HAM-D-17)
Time frame: Baseline and Day 60
The HAM-D-17 is a multiple choice questionnaire that clinicians may use to rate the severity of a patient's major depression. Items are scored on a scale of zero to four and higher scores indicate greater impairment. This scale is scored by summing the scores on each item and scores can range from 0-68. When assessing changes in HAMD score, negative changes indicate improvement (i.e. the score has decreased) and positive scores indicate a worsening of symptoms (i.e. scores have increased).
1 secondary outcome
The Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR)
Time frame: Baseline and Day 60
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26613389Shelton RC, Pencina MJ, Barrentine LW, Ruiz JA, Fava M, Zajecka JM, Papakostas GI. Association of obesity and inflammatory marker levels on treatment outcome: results from a double-blind, randomized study of adjunctive L-methylfolate calcium in patients with MDD who are inadequate responders to SSRIs. J Clin Psychiatry. 2015 Dec;76(12):1635-41. doi: 10.4088/JCP.14m09587.
- Derived from this study: PubMed 24813065Papakostas GI, Shelton RC, Zajecka JM, Bottiglieri T, Roffman J, Cassiello C, Stahl SM, Fava M. Effect of adjunctive L-methylfolate 15 mg among inadequate responders to SSRIs in depressed patients who were stratified by biomarker levels and genotype: results from a randomized clinical trial. J Clin Psychiatry. 2014 Aug;75(8):855-63. doi: 10.4088/JCP.13m08947.
- 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, MD principal investigator
Massachusetts General Hospital
6 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(Deplin) in people with Depression, run by George I. Papakostas at 6 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 28 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 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. 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 18 Jan 2013). 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?
The 17-item Hamilton Depression Scale (HAM-D-17) (time frame: Baseline and Day 60). 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 NCT00955955, which also lists 3 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 28 Apr 2017.