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Trial record 2 of 188 for:    TNF-α depression

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

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ClinicalTrials.gov Identifier: NCT02553915
Recruitment Status : Recruiting
First Posted : September 18, 2015
Last Update Posted : August 29, 2017
Sponsor:
Collaborator:
Emory University
Information provided by (Responsible Party):
David Mischoulon, MD, Massachusetts General Hospital

Brief 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.

Condition or disease Intervention/treatment Phase
Major Depressive Disorder Overweight Inflammation Other: Placebo Drug: EPA 1 g/day Drug: EPA 2 g/day Drug: EPA 4 g/day Phase 2 Phase 3

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Omega-3 Fatty Acids for MDD With High Inflammation: A Personalized Approach
Study Start Date : December 2015
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : June 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
Soybean oil placebo capsules, 4 capsules daily for 12 weeks
Other: Placebo
Soybean oil placebo

Experimental: EPA 1 g/day
Eicosapentaenoic acid (EPA) 1000 mg capsules, 1 daily (plus 3 placebo capsules) for 12 weeks
Other: Placebo
Soybean oil placebo

Drug: EPA 1 g/day
Omega-3 fatty acid extracted from fish oil, 1 g/day
Other Name: Eicosapentaenoic acid; omega-3 fatty acid

Experimental: EPA 2 g/day
Eicosapentaenoic acid (EPA) 1000 mg capsules, 2 daily (plus 2 placebo capsules) for 12 weeks
Other: Placebo
Soybean oil placebo

Drug: EPA 2 g/day
Omega-3 fatty acid extracted from fish oil, 2 g/day
Other Name: Eicosapentaenoic acid; omega-3 fatty acid

Experimental: EPA 4 g/day
Eicosapentaenoic acid (EPA) 1000 mg capsules, 4 daily for 12 weeks
Drug: EPA 4 g/day
Omega-3 fatty acid extracted from fish oil, 4 g/day
Other Name: Eicosapentaenoic acid; omega-3 fatty acid




Primary Outcome Measures :
  1. Mean change in plasma concentration of inflammatory biomarkers [ Time Frame: 12 weeks ]
    To evaluate whether a dose-response relationship exists between dose of EPA and decrease either in plasma IL-6 levels or in mitogen-stimulated PBMC TNF-α expression and secretion, when compared with placebo.

  2. Mean change in depression severity score [ Time Frame: 12 weeks ]
    To evaluate whether EPA treatment produces a decrease in ratings of depression severity, when compared with placebo-treated subjects; and whether the changes in IL-6 or mitogen- stimulated PBMC TNF-α expression will mediate changes observed in ratings of depression.


Secondary Outcome Measures :
  1. Mean change in plasma concentration of mitogen-stimulated PBMC IL-6 [ Time Frame: 12 weeks ]
    To evaluate whether EPA treatment produces decreases in mitogen-stimulated PBMC IL-6

  2. Mean change in plasma levels of secondary inflammation pathway-related biomarkers [ Time Frame: 12 weeks ]
    To evaluate whether EPA treatment produces decreases in plasma TNF-α, leptin, hs-CRP, and IL-1ra levels

  3. Mean changes in levels of expression of inflammation-related genes [ Time Frame: 12 weeks ]
    To evaluate whether EPA treatment produces decreases in the expression of inflammation pathway-related genes



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02553915


Contacts
Contact: Mark H Rapaport, MD 404-727-8382 mrapapo@emory.edu
Contact: David Mischoulon, MD,PhD 617-724-5198 dmischoulon@partners.org

Locations
United States, Georgia
Emory University School of Medicine Recruiting
Atlanta, Georgia, United States, 30322
Contact: Mark H Rapaport, MD    404-727-8382    mrapapo@emory.edu   
Contact: Becky Kinkead, PhD    404-727-3719    bkinkea@emory.edu   
United States, Massachusetts
Depression Clinical and Research Program at Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: David Mischoulon, MD, PhD    617-724-5198    dmischoulon@partners.org   
Contact: Maurizio Fava, MD    617-724-2513    mfava@partners.org   
Principal Investigator: David Mischoulon, MD, PhD         
Principal Investigator: Maurizio Fava, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Emory University
Investigators
Principal Investigator: Maurizio Fava, MD Massachusetts General Hospital

Responsible Party: David Mischoulon, MD, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02553915     History of Changes
Other Study ID Numbers: R01AT008857-01
First Posted: September 18, 2015    Key Record Dates
Last Update Posted: August 29, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by David Mischoulon, MD, Massachusetts General Hospital:
Omega-3
EPA
Depression
Overweight
Inflammation
Eicosapentaenoic acid

Additional relevant MeSH terms:
Depressive Disorder
Depression
Depressive Disorder, Major
Inflammation
Overweight
Pathologic Processes
Mood Disorders
Mental Disorders
Behavioral Symptoms
Body Weight
Signs and Symptoms