Specialized Pro-resolving Lipid Mediators and Treatment Resistant Depression

NCT05774665 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: R33AT012329
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this clinical trial is to determine the impact of omega-3 fatty acids on the production of anti-inflammatory effects and clinical improvement in people with depression who have not responded well to standard antidepressant treatment. The main questions it seeks to answer are:

1. 1.Do omega-3 fatty acids added to ineffective antidepressant treatment increase production of compounds that reduce inflammation?
2. 2.Is the increase in these anti-inflammatory compounds associated with a stronger antidepressant effect?
3. 3.an omega-3 preparation
4. 4.an inactive placebo

Conditions

Treatment Resistant Depression; Inflammation; Overweight

Keywords

omega-3; fatty acid; major depressive disorder

Outcome Measures

Primary Outcomes (1)

• 18-HEPE (18-hydroxy eicosapentaeoic acid) Change

  Evaluate change in plasma 18-HEPE (18-hydroxy eicosapentaeoic acid) levels associated with 12 weeks of 4 g/day EPA-enriched n-3 treatment vs placebo.

  12 weeks

Secondary Outcomes (1)

• 18-HEPE (18-hydroxy eicosapentaeoic acid) Change in Treatment Responders

  12 weeks

Study Arms (2)

Omega-3

EXPERIMENTAL

Omega-3 fatty acid (ProEPA Xtra) capsules containing a total of 4 g/day of eicosapentaenoic acid (EPA), administered for 12 weeks.

Drug: Omega 3

Placebo

PLACEBO COMPARATOR

Placebo capsules containing soybean oil (about 54% omega-6 and 6% omega-3, but no EPA or docosahexaenoic acid (DHA)), and matched to the ProEPA Xtra capsules in terms of appearance, odor, and taste.

Other: Placebo

Interventions

Omega 3 DRUG

Omega-3 fatty acid enriched for eicosapentaenoic acid (EPA)

Also known as: EPA

Omega-3

Placebo OTHER

Placebo consisting of soybean oil (about 54% omega-6 and 6% omega-3, but no EPA or docosahexaenoic acid (DHA)).

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:

• Age: 18 to 65 years
• Patients with treatment-resistant MDD who have not responded to at least 2 and no more than 5 antidepressant trials of at least 8 weeks duration during the current episode and have been on a current stable antidepressant regiment for at least 4 weeks. The diagnosis of MDD will be confirmed using the MINI and the historical failure to respond to antidepressant therapy will be documented using the Antidepressant Treatment Response Questionnaire (ATRQ), with failure to respond defined as less than 50% improvement by subject history.
• hs-CRP ≥ 3 mg/L and ≤ 10 mg/L
• BMI \>25 kg/m2 and ≤ 40 kg/m2
• item Hamilton Depression Rating Scale (HAM-D) score ≥15, and \<25% decrease in score between screen and baseline

You may not qualify if:

• Meeting lifetime DSM-5 criteria for: a neurocognitive disorder, psychotic disorder, bipolar disorder, obsessive compulsive disorder, bulimia nervosa, or anorexia nervosa in the 3 months prior to the screening; any substance use disorder (except for nicotine or caffeine use disorder).
• Patients who, in the investigator's judgment, pose a current, serious suicidal or homicidal risk
• Presence of a serious or unstable medical illness, including insulin-dependent diabetes mellitus or bleeding disorder which, in the investigator's opinion, could compromise response to treatment, participant safety, or interpretation of study results.
• Currently breastfeeding, pregnant women, or women of childbearing ability, who do NOT agree to use a study approved method of birth control (described in the MOP) for the duration of the study.
• Currently or within 90 days of screen participating in another clinical trial (excluding large natural cohort trials such as 'All of Us').
• Failure to respond during the course of the current major depressive episode to \>5 adequate antidepressant trials
• Current use of antipsychotic medications or lithium
• Having received ketamine therapy within 90 days of the screening visit
• Patients who have initiated psychotherapy ≤ 90 days prior to screening.Having received electroconvulsive therapy during the current depressive episode or within 6 months of the screening visit
• Concomitant use of any psychotropic agents within 2 weeks of the baseline visit, except for the ongoing antidepressant, prescription hypnotics, diphenhydramine, or a stable daily dose of a benzodiazepine.
• Concomitant medications that might confound the biomarker findings within 1 week of the baseline visit and during the trial, including: regular (i.e. more than three times per week) ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase (COX)-2 inhibitors; any use of oral steroids, immunosuppressants, interferon, chemotherapy, or anticoagulants.
• A history of severe sensitivity to soy products, fish products, or PUFA supplements
• Patients who had taken supplements enriched with n-3 fatty acids within 60 days of the screening visit or who, at baseline, were consuming a diet containing \> 3 g/day of n-3 fatty acids, or who consume \> 2 meals of fatty fish per week.
• Having taken a supplement of ≥1 g/day of n-3 fatty acids for ≥6 weeks during the current major depressive episode
• Patients who have had either a poor response or intolerable side effects from n-3s in the past.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• University of Utah: collaborator
• Emory University: collaborator

Study Sites (3)

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Depression Clinical and Research Program at Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Related Publications (1)

• Mischoulon D, Dunlop BW, Kinkead B, Schettler PJ, Lamon-Fava S, Rakofsky JJ, Nierenberg AA, Clain AJ, Mletzko Crowe T, Wong A, Felger JC, Sangermano L, Ziegler TR, Cusin C, Fisher LB, Fava M, Rapaport MH. Omega-3 Fatty Acids for Major Depressive Disorder With High Inflammation: A Randomized Dose-Finding Clinical Trial. J Clin Psychiatry. 2022 Aug 22;83(5):21m14074. doi: 10.4088/JCP.21m14074.

  PMID: 36005883 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Inflammation; Overweight; Depressive Disorder, Major

Interventions

Docosahexaenoic Acids

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Fatty Acids, Omega-3; Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fatty Acids, Unsaturated; Fatty Acids; Fish Oils; Oils

Study Officials

• Mark H Rapaport, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study will be placebo controlled. Participants will receive identical capsules with omega-3 fatty acids or placebo. Randomization will be set by our research pharmacy and no participants or study personnel will know treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Depression Clinical and Research Program

Model Details: Double blind randomized placebo controlled clinical trial

Study Record Dates

• First Submitted: March 6, 2023
• First Posted: March 20, 2023
• Study Start: January 30, 2025
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Following publication of main study findings.
• Access Criteria: Interested investigators should contact the study team to inquire about data availability.

Locations

US (3)