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

Phase 4

Completed

• Conditions: Depression
• Interventions: Other: 6(S)-5-MTHF(Deplin); Other: Placebo

• Registration Number: NCT00955955
• Lead Sponsor: George I. Papakostas

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.

Study Timeline

• Study Start: 2009-07
• Study First Submitted: 2009-07-30
• Study First Submitted QC: 2009-08-07
• Study First Posted: 2009-08-10
• Primary Completion: 2011-04
• Study Completion: 2011-04
• Results First Submitted: 2012-10-31
• Results First Submitted QC: 2012-12-11
• Results First Posted: 2013-01-18
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-28
• Last Update Posted: 2017-04-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 75

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo/Deplin	6(S)-5-MTHF(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
Placebo/Deplin	Placebo	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
6(S)-5-MTHF(Deplin)	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/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

Primary Outcome Measures

Name	Time	Method
The 17-item Hamilton Depression Scale (HAM-D-17)	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).

Secondary Outcome Measures

Name	Time	Method
The Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR)	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.

Trial Locations

Locations (6)

University of California San Diego School of Medicine; 🇺🇸 San Diego, California, United States

Rush University Medical Center, Psychiatric Medicine Associates, LLC; 🇺🇸 Chicago, Illinois, United States

University of Cincinnati, College of Medicine; 🇺🇸 Cincinnati, Ohio, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States