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

NCT00955955 | Completed Phase 4 Results

• 1 other identifier: 2006P000604 (2)
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 6

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).

Conditions

Depression

Keywords

Depression; Medical food

Outcome Measures

Primary Outcomes (1)

• 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).

  Baseline and Day 60

Secondary Outcomes (1)

• The Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR)

  Baseline and Day 60

Study Arms (3)

6(S)-5-MTHF(Deplin)

EXPERIMENTAL

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)

Placebo/Deplin

EXPERIMENTAL

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); Other: Placebo

Placebo/Placebo

EXPERIMENTAL

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

Interventions

6(S)-5-MTHF(Deplin) OTHER

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

6(S)-5-MTHF(Deplin); Placebo/Deplin

Placebo OTHER

Inactive substance

Placebo/Deplin; Placebo/Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• George I. Papakostas: lead
• Pamlab, L.L.C.: collaborator

Study Sites (6)

University of California San Diego School of Medicine

San Diego, California, 92093, United States

Location

Rush University Medical Center, Psychiatric Medicine Associates, LLC

Chicago, Illinois, 60612, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Cincinnati, College of Medicine

Cincinnati, Ohio, 45221, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (3)

• 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.

  PMID: 26613389 DERIVED

• 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.

  PMID: 24813065 DERIVED

• 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.

  PMID: 23212058 DERIVED

MeSH Terms

Conditions

Depression

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Results Point of Contact

• Title: Dr. George Papakostas- Director of Treatment Resistant Depression Studies
• Organization: Massachusetts General Hospital- Depression Clinical and Research Program

gpapakostas@partners.org

617-726-6697

Study Officials

• George I. Papakostas, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Treatment Resistant Depression Studies-DCRP

Study Record Dates

• First Submitted: July 30, 2009
• First Posted: August 10, 2009
• Study Start: July 1, 2009
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: April 28, 2017
• Results First Posted: January 18, 2013

Record last verified: 2017-03

Locations

US (6)