A PET Study With [11C]PBR-28 and an Experimental Medication, Ethyl Eicosapentaenoic Acid

This pilot study will ask whether omega three fatty acids have an antidepressant effect in bipolar depression by decreasing brain inflammation.

Study Overview

• Status: Withdrawn
• Conditions: Bipolar Disorder
• Intervention / Treatment: Drug: Ethyl Eicosapentaenoic Acid

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute/Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ability to provide informed consent
2. Diagnosis of of bipolar I or bipolar 2 disorder and currently meets criteria for a major depressive episode
3. Depression of sufficient severity to score at least 16 on the first 17 items of the Hamilton Depression Rating Scale including the atypical depression items addendum at the time of recruitment
4. Age range 18-60
5. Females of child-bearing potential must be willing to use an acceptable method of birth control throughout the study. These include abstinence, birth control pill, male condom, IUD, depo-provera, Norplant male sterilization, female sterilization

6. Not taking more than two psychotropic medications at time of recruitment to avoid polypharmacy. Participants will not have changed the dose of the medication for at least 8 weeks before enrollment.

   Only participants with bipolar 2 disorder diagnosis may be off psychotropic medications at time of enrollment. In that case, they must not have stopped any medications within 8 weeks of enrollment.

   Participants can be taking diphenhydramine but no benzodiazepines or other hypnotics as needed at time of enrollment.

7. Genotyping as a medium or high TSPO binding type

Exclusion Criteria:

1. Diagnosis of any other major psychiatric disorders such as lifetime schizophrenia, schizoaffective disorder, current psychotic features of bipolar disorder, or recent moderate substance use disorder (within 4 months of recruitment); IV drug use. Meets DSMV criteria for a manic episode, or Young Mania Rating Scale score >12, at the time of screening.
2. Previous failed trial or intolerable side effects of ethyl EPA or any other form of omega 3 fatty acids
3. A first-degree family history of schizophrenia if the participant is less than 33 years old.
4. Significant active physical illness, including blood dyscrasias, lymphomas, hypersplenism, endocrinopathies, renal failure, chronic obstructive lung disease, autonomic neuropathies, peripheral vascular disease. Any disorders with inflammation, malignancy, autoimmune or infectious etiology. Systemic blood pressure >140 or diastolic blood pressure >100. Hemoglobin <11 in females or <13 in males.
5. Actively suicidal, as defined by expressing ideation with a plan or intent for suicide or develops suicidal ideation that requires immediate medical or treatment intervention.
6. Pregnancy, abortion or miscarriage in the two months prior to enrollment or plans to conceive during the course of the study participation
7. Lactating Women
8. ECT within the last 6 months
9. Participants who endorse a history of prior head trauma and score 1.5 standard deviations below the mean on Trailmaking A & B test
10. Metal implants, pacemaker, metal prostheses, metal orthodontic appliances or shrapnel in the body

11. Current, past or anticipated exposure to radiation, including

    1. Having been badged for radiation exposure in the workplace
    2. Participation in nuclear medicine protocols in the last year* *Participants will be eligible, however, if the injected dose and dosimetry of the radiotracer are known and the cumulative annual exposure of the previous studies and this study is lower than the annual limit for research participants defined by FDA (21 CFR 361.1)
12. History of claustrophobia that would prevent the participation in neuroimaging

13. Weight >350 lbs or inability to fit into the MRI scanner**

    ** If there are doubts that the MRI scanner can accommodate the physical dimensions of the participant, the participant's circumference may be measured to determine if it is less than the MR scanner limit of 55 cm. The participant may also be brought to the MRI Center and the MRI technologist will assess whether the participant will be able to fit into the MRI scanner. Metal screening and urine pregnancy testing will be done in this circumstance before the participant enters the MRI area.

14. Current anticoagulant or anti-platelet treatment including aspirin if needed daily
15. Risks of delay to treatment of known efficacy (up to 9 weeks) are too great for the participant. Risks to consider include A) Severity of presenting symptoms B) History of symptom fluctuations or deterioration C) Psychosocial conditions that make delay to treatment unreasonable

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ethyl eicosapentaenoic acid; Ethyl eicosapentaenoic acid will be given at 1G by mouth twice per day	Drug: Ethyl Eicosapentaenoic Acid; Treatment will be for six weeks; Other Names: Ethyl EPA; icosapent ethyl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery Asberg Rating Scale	Minimum value of 0, maximum value of 60; Greater score reflects greater depression severity	Six weeks

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2021
• Primary Completion (Actual): July 1, 2022
• Study Completion (Actual): July 1, 2022

Study Registration Dates

• First Submitted: March 19, 2021
• First Submitted That Met QC Criteria: March 19, 2021
• First Posted (Actual): March 23, 2021

Study Record Updates

• Last Update Posted (Actual): October 14, 2022
• Last Update Submitted That Met QC Criteria: October 12, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Bipolar and Related Disorders; Bipolar Disorder; Platelet Aggregation Inhibitors; Lipid Regulating Agents; Eicosapentaenoic acid ethyl ester
• Other Study ID Numbers: 8044 (Other Identifier: DUMC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No