Overview

Omega-3 Fatty Acids for Major Depressive Disorder With High Inflammation: A Personalized Approach

Status:
Active, not recruiting
Trial end date:
2021-12-31
Target enrollment:
0
Participant gender:
All
Summary
This project aims to evaluate whether a dose-response relationship exists between dose of polyunsaturated fatty acids (PUFA), delivered as eicosapentaenoic acid (EPA), and change in markers of inflammation, and whether these effects differ from placebo. A key secondary aim is to evaluate the antidepressant effectiveness of EPA in overweight adult outpatients with current major depressive disorder (MDD). To address these aims, the project will use a four-arm, randomized, parallel-group, placebo-controlled design comparing placebo versus three doses of EPA (1 gm/day, 2 gm/day, or 4 gm/day) administered over 12 weeks. The study is to be conducted at two sites: Emory University School of Medicine, and Massachusetts General Hospital. Eligible participants will be between the ages of 18-80 who have current MDD, are overweight, and who demonstrate peripheral inflammation, defined as an high sensitivity C-reactive protein (hs-CRP) level ≥ 3 mg/L. The primary outcome will be change in plasma interleukin-6 (IL-6) levels and/or mitogen-stimulated peripheral blood mononuclear cells (PBMC) Tumor Necrosis Factor-alpha (TNF-α) expression levels in EPA- versus placebo-treated participants. The results of this investigation are intended to be used to design and power a larger definitive test of the efficacy and biological effects of EPA in patients with major depressive disorder.
Phase:
Phase 2/Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Massachusetts General Hospital
Collaborator:
Emory University
Criteria
Inclusion Criteria:

- Able to provide informed consent.

- Men or women aged 18-80 years.

- A primary psychiatric diagnosis of major depressive disorder (MDD), by Diagnostic and
Statistical Manual-5th ed (DSM-5) using the Mini International Neuropsychiatric
Interview (MINI v.7.0).

- A Screening and Baseline visit Inventory of Depressive Symptoms, Clinician rated
(IDS-C30) total score ≥ 25.

- Currently overweight at screening, defined as BMI > 25 kg/m2.

- Screening visit high-sensitivity C-reactive protein concentration ≥ 3 mg/L.

- Willing to not significantly modify their diet from the time they sign consent through
the end of study participation.

Exclusion Criteria:

- Use of any psychotropic agents within 2 weeks of baseline or at any time during the
study, with the exception of prescription hypnotics (eszopiclone, zaleplon, zolpidem,
suvorexant, ramelteon), diphenhydramine, or a stable daily dose of a benzodiazepine.

- Breastfeeding or pregnant women, women intending to become pregnant within 6 months of
the screening visit, or women of child bearing potential who are not using a medically
accepted means of contraception (defined as oral contraceptive pill or implant,
condom, diaphragm, intrauterine device (IUD), status-post tubal ligation, or partner
with vasectomy)

- Patients who, in the investigator's judgement, pose a current, serious suicidal or
homicidal risk.

- Serious or unstable medical illness that in the investigator's opinion could
compromise response to treatment or interpretation of study results.

- History of seizure disorder, except for childhood febrile seizures.

- Meeting DSM-5 criteria at any point in their lifetime, for any of the following:
Neurocognitive Disorder, Psychotic Disorder, Bipolar disorder, Anorexia Nervosa

- Meeting DSM-5 criteria in the 3 months prior to the screening visit for any Substance
Use Disorder (except nicotine or caffeine).

- Meeting DSM-5 criteria at screening for current obsessive compulsive disorder or
bulimia nervosa.

- Presence of psychotic features at any time during the current major depressive
episode.

- Any conditions or medications (within 1 week of baseline or during the trial) that
might confound the biomarker findings, including: Regular ingestion of NSAIDs or
Cyclooxygenase-2 (COX-2) inhibitors, or any use of oral steroids, immunosuppressants,
interferon, chemotherapy, or anticoagulants (Patients will be instructed not to take a
nonsteroidal antiinflammatory drug (NSAID) or COX-2 inhibitor in the 24 hours prior to
a biomarker assessment visit), Malignancy not in remission for at least 1 year, Active
autoimmune disorder or inflammatory bowel disease, Insulin-dependent diabetes
mellitus.

- History of allergy to PUFA supplements.

- Laboratory evidence of undiagnosed hypothyroidism or change in treatment for
hypothyroidism in the 3 months prior to screening.

- Patients who have failed to respond during the course of their current major
depressive episode to >4 adequate antidepressant trials, defined as six weeks or more
of treatment with the FDA-defined minimally effective dose.

- Patients who have taken a supplement of at least 1 g/day of omega 3 fatty acids for at
least 6 weeks during the current major depressive episode.

- Patients who have had electroconvulsive therapy (ECT) during the current depressive
episode or within 6 months of the screening visit.

- Patients who have taken supplements with omega-3 fatty acids (see Appendix A for list
of products) within sixty (60) days of the screening visit.

- Patients who, at baseline, are consuming a diet that contains more than 3g/day of
omega-3 FA, or who consume more than 3 meals of fatty fish per week.

- Patients who have a history of a bleeding disorder.

- Patients who have participated in another clinical trial of an investigational
medication within 1 month of the screening visit.

- Patients who are currently in psychotherapy that was initiated within 90 days prior to
the study screening visit.