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: May 7, 2013
Last verified: May 2013
  Purpose

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).


Condition Intervention Phase
Depression
Other: 6(S)-5-MTHF(Deplin)
Other: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: TRD - 2: A Double-Blind, Placebo Controlled Study of 6(S)-5-MTHF Among SSRI-Resistant Outpatients With Major Depressive Disorder (MDD)

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • 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).



Secondary Outcome Measures:
  • 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.



Enrollment: 75
Study Start Date: July 2009
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Other: 6(S)-5-MTHF(Deplin)
Deplin is a medical food. Patients will take 15 mg/day of 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

Other: 6(S)-5-MTHF(Deplin)
Deplin is a medical food. Patients will take 15 mg/day of deplin.
Other: Placebo
Inactive substance
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

Other: Placebo
Inactive substance

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00955955

Locations
United States, California
University of California San Diego School of Medicine
San Diego, California, United States, 92093
United States, Illinois
Rush University Medical Center, Psychiatric Medicine Associates, LLC
Chicago, Illinois, United States, 60612
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Ohio
University of Cincinnati, College of Medicine
Cincinnati, Ohio, United States, 45221
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
George I. Papakostas
Pamlab, L.L.C.
Investigators
Principal Investigator: George I. Papakostas, MD Massachusetts General Hospital
  More Information

No publications provided by Massachusetts General Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: George I. Papakostas, Director of Treatment Resistant Depression Studies-DCRP, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00955955     History of Changes
Other Study ID Numbers: 2006P000604 (2)
Study First Received: July 30, 2009
Results First Received: October 31, 2012
Last Updated: May 7, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Depression
Medical food

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mental Disorders
Mood Disorders
Serotonin Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Serotonin Agents

ClinicalTrials.gov processed this record on October 21, 2014