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

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00321152
• Collaborator: Pamlab, L.L.C. (Industry)
• Enrollment: 150
• Locations: 11
• Arms: 3
• Duration (Months): 43
• Patients Per Site: 13.6
• Patients Per Site Per Month: 0.3

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Other: 6(S)-5-MTHF (a Medical Food)	Phase 4

Detailed Description

The study consists of two sequential phases, each lasting a total of four weeks (8 weeks total), with visits every 10 days. Once patients agree to participate in the study by signing the informed consent document, a full medical and psychiatric history will be taken and a physical examination and blood draw will be performed. Screen rating scales will be performed. Screened and eligible patients will be asked to return two weeks later for a baseline visit when they will be randomized to double-blind treatment with placebo or Deplin (6(S)-5-MTHF). The double-blind treatment will last 60 days, during which patients will be seen every 10 days. Subjects will be randomized to one of three treatment groups: a)Deplin/Deplin, b) placebo/Deplin, c) placebo/placebo. Patients will have a greater than 50% chance of receiving active medication (Deplin) at some point in the 8 week study

• For patients randomly assigned to the Deplin/Deplin sequence, the dose of 6(S)-5-MTHF will be 7.5 mg/day during the first phase of the study, and 15 mg/d during the second phase of the study.

• For patients randomly assigned to the placebo/Deplin sequence, the dose of 6(S)-5-MTHF will be 7.5 mg/day during the second phase of the study.

• For patients randomly assigned to the placebo/placebo sequence, both tablets of study medication will be placebo during both phases of the study.

All patients will be asked to take two tablets of blinded study medication in the morning, in addition to their stable dose of ongoing SSRI treatment. Each study medication tablet will be either 7.5 mg of 6(S)-5-MTHF or matching placebo.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Placebo Controlled Study of 6(S)-5-MTHF Among SSRI-Resistant Outpatients With Major Depressive Disorder (MDD)
• Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Deplin/Deplin = participants will receive 7.5 mg/day of Deplin (6(S)-5-MTHF)for the first 4 weeks, and then 15 mg/day of Deplin for the next 4 weeks.	Other: 6(S)-5-MTHF (a Medical Food); The study consists of 8 visits over a period of 8 weeks or 60 days. Eligible participants will be randomized to double-blind treatment with placebo or Deplin (6(S)-5-MTHF). Participants will have a greater than 50% chance of receiving active medication (Deplin) at some point in the 8 week study. At the end of the double-blind phase, both responders and non-responders who have completed the 8 week study will have the option of receiving free, open-label adjunctive treatment with either 7.5 mg or 15 mg of 6(S)-5-MTHF for 12 months. Subjects who agree to receive open-label treatment with 6(S)-5-MTHF for 12 months will be assessed every three (3) months until the end of the follow-up phase.
Experimental: 2 placebo/Deplin = participants will receive placebo for the first 4 weeks, and then 7.5 mg/day of Deplin (6(S)-5-MTHF) for the next 4 weeks.	Other: 6(S)-5-MTHF (a Medical Food); The study consists of 8 visits over a period of 8 weeks or 60 days. Eligible participants will be randomized to double-blind treatment with placebo or Deplin (6(S)-5-MTHF). Participants will have a greater than 50% chance of receiving active medication (Deplin) at some point in the 8 week study. At the end of the double-blind phase, both responders and non-responders who have completed the 8 week study will have the option of receiving free, open-label adjunctive treatment with either 7.5 mg or 15 mg of 6(S)-5-MTHF for 12 months. Subjects who agree to receive open-label treatment with 6(S)-5-MTHF for 12 months will be assessed every three (3) months until the end of the follow-up phase.
Placebo Comparator: 3 placebo/placebo = both tablets of study medication will be placebo during both phases of the study.	Other: 6(S)-5-MTHF (a Medical Food); The study consists of 8 visits over a period of 8 weeks or 60 days. Eligible participants will be randomized to double-blind treatment with placebo or Deplin (6(S)-5-MTHF). Participants will have a greater than 50% chance of receiving active medication (Deplin) at some point in the 8 week study. At the end of the double-blind phase, both responders and non-responders who have completed the 8 week study will have the option of receiving free, open-label adjunctive treatment with either 7.5 mg or 15 mg of 6(S)-5-MTHF for 12 months. Subjects who agree to receive open-label treatment with 6(S)-5-MTHF for 12 months will be assessed every three (3) months until the end of the follow-up phase.

Outcome Measures

Primary Outcome Measures

1. HAM-D [every visit]

Secondary Outcome Measures

1. QIDS-SR [every visit]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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), or any psychotic disorder (current or past).

• Have failed more than 2 adequate antidepressant trials during the current Major Depressive Episode.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Diego School of Medicine	San Diego	California	United States	92161
2	Rush University Medical Center, Psychiatric Medicine Associates, LLC	Chicago	Illinois	United States	60612
3	Lousiana State University Health Sciences Center	New Orleans	Louisiana	United States	70115
4	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
5	Burlington Medical Associates	Burlington	Massachusetts	United States	01803
6	Waltham Family Practice	Waltham	Massachusetts	United States	02453
7	Charles River Medical Associates	Westborough	Massachusetts	United States	01581
8	Univeristy of Cincinnati, College of Medicine	Cincinnati	Ohio	United States	45267
9	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
10	Southeast Health Consultants, LLC	Charleston	South Carolina	United States	29407
11	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37212

Sponsors and Collaborators

• Massachusetts General Hospital
• Pamlab, L.L.C.

Investigators

• Principal Investigator: George I Papakostas, M.D, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00321152
• Other Study ID Numbers: 2006P000604
• First Posted: May 3, 2006
• Last Update Posted: Jun 8, 2010
• Last Verified: Jun 1, 2010

• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major

Study Results

No Results Posted as of Jun 8, 2010