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

March 28, 2017 updated by: George I. Papakostas

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).

Study Overview

Status

Completed

Conditions

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 Type

Interventional

Enrollment (Actual)

75

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • San Diego, California, United States, 92093
        • University of California San Diego School of Medicine
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center, Psychiatric Medicine Associates, LLC
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Ohio
      • Cincinnati, Ohio, United States, 45221
        • University of Cincinnati, College of Medicine
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

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

Deplin is a medical food. Patients will take 15 mg/day of deplin.
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

Inactive substance

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).

Baseline and Day 60

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR)
Time Frame: Baseline and Day 60

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.

Baseline and Day 60

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2009

Primary Completion (Actual)

April 1, 2011

Study Completion (Actual)

April 1, 2011

Study Registration Dates

First Submitted

July 30, 2009

First Submitted That Met QC Criteria

August 7, 2009

First Posted (Estimate)

August 10, 2009

Study Record Updates

Last Update Posted (Actual)

April 28, 2017

Last Update Submitted That Met QC Criteria

March 28, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Other Study ID Numbers

  • 2006P000604 (2)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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