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

Primary Purpose

Depression

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
6(S)-5-MTHF(Deplin)
Placebo
Sponsored by
George I. Papakostas
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Depression focused on measuring Depression, Medical food

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California San Diego School of Medicine
  • Rush University Medical Center, Psychiatric Medicine Associates, LLC
  • Massachusetts General Hospital
  • University of Cincinnati, College of Medicine
  • University of Pennsylvania
  • Vanderbilt University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

6(S)-5-MTHF(Deplin)

Placebo/Deplin

Placebo/Placebo

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.

Full Information

First Posted
July 30, 2009
Last Updated
March 28, 2017
Sponsor
George I. Papakostas
Collaborators
Pamlab, L.L.C.
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1. Study Identification

Unique Protocol Identification Number
NCT00955955
Brief Title
Study of 6(S)-5-MTHF Among Selective Serotonin Reuptake Inhibitor-Resistant Outpatients With Major Depressive Disorder
Acronym
TRD-2
Official Title
TRD - 2: A Double-Blind, Placebo Controlled Study of 6(S)-5-MTHF Among SSRI-Resistant Outpatients With Major Depressive Disorder (MDD)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
April 2011 (Actual)
Study Completion Date
April 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
George I. Papakostas
Collaborators
Pamlab, L.L.C.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depression
Keywords
Depression, Medical food

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
75 (Actual)

8. Arms, Groups, and Interventions

Arm Title
6(S)-5-MTHF(Deplin)
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo/Deplin
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo/Placebo
Arm Type
Experimental
Arm Description
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 Type
Other
Intervention Name(s)
6(S)-5-MTHF(Deplin)
Intervention Description
Deplin is a medical food. Patients will take 15 mg/day of deplin.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Inactive substance
Primary Outcome Measure Information:
Title
The 17-item Hamilton Depression Scale (HAM-D-17)
Description
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).
Time Frame
Baseline and Day 60
Secondary Outcome Measure Information:
Title
The Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR)
Description
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.
Time Frame
Baseline and Day 60

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
George I. Papakostas, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California San Diego School of Medicine
City
San Diego
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Rush University Medical Center, Psychiatric Medicine Associates, LLC
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
University of Cincinnati, College of Medicine
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45221
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
26613389
Citation
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.
Results Reference
derived
PubMed Identifier
24813065
Citation
Papakostas 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.
Results Reference
derived
PubMed Identifier
23212058
Citation
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;169(12):1267-74. doi: 10.1176/appi.ajp.2012.11071114.
Results Reference
derived

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

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