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Study of 6(S)-5-MTHF Among Selective Serotonin Reuptake Inhibitor-Resistant Outpatients With Major Depressive Disorder (TRD-2)

This study has been completed.
Sponsor:
Collaborator:
Pamlab, L.L.C.
Information provided by (Responsible Party):
George I. Papakostas, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00955955
First received: July 30, 2009
Last updated: April 9, 2013
Last verified: April 2013
History of Changes

July 30, 2009
April 9, 2013
July 2009
April 2011   (final data collection date for primary outcome measure)
The 17-item Hamilton Depression Scale (HAM-D-17) [ Time Frame: Baseline and Day 60 ] [ Designated as safety issue: No ]

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).
The 28-item Hamilton Depression Scale (HAM-D-28) [ Time Frame: Screen, Baseline, Day 10, Day 20, Day 30, Day 40, Day 50, Day 60, Day 150, Day 240, Day 330, Day 420 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00955955 on ClinicalTrials.gov Archive Site
The Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR) [ Time Frame: Baseline and Day 60 ] [ Designated as safety issue: No ]

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:

  1. Enter the highest score from questions 1-4 (sleep items): ______
  2. Enter score on item 5 ____
  3. Enter the highest score from questions 6-9 (appetite/weight): ______
  4. Enter score on item 10 ____
  5. Enter score on item 11 ____
  6. Enter score on item 12 ____
  7. Enter score on item 13 ____
  8. Enter score on item 14 ____
  9. 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.
The Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR), 16-item [ Time Frame: Screen, Baseline, Day 10, Day 20, Day 30, Day 40, Day 50, Day 60, Day 150, Day 240, Day 330, Day 420 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Study of 6(S)-5-MTHF Among Selective Serotonin Reuptake Inhibitor-Resistant Outpatients With Major Depressive Disorder
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).

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.
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Depression
  • Other: 6(S)-5-MTHF(Deplin)
    Deplin is a medical food. Patients will take 15 mg/day of deplin.
  • Other: Placebo
    Inactive substance
  • Experimental: 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

    Intervention: Other: 6(S)-5-MTHF(Deplin)
  • Experimental: Placebo/Deplin

    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

    Interventions:
    • Other: 6(S)-5-MTHF(Deplin)
    • Other: Placebo
  • Experimental: Placebo/Placebo

    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

    Intervention: Other: Placebo
Papakostas 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 1;169(12):1267-74. doi: 10.1176/appi.ajp.2012.11071114.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
75
April 2011
April 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 18-65 years old
  • Meet criteria for current Major Depressive Disorder
  • Currently taking an SSRI

Exclusion Criteria:

  • 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
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00955955
2006P000604 (2)
No
George I. Papakostas, Massachusetts General Hospital
George I. Papakostas
Pamlab, L.L.C.
Principal Investigator: George I. Papakostas, MD Massachusetts General Hospital
Massachusetts General Hospital
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP