Treating Insulin Resistance as a Strategy to Improve Outcome in Refractory Bipolar Disorder

Last updated: January 12, 2021
Sponsor: Cynthia Calkin
Overall Status: Completed

Phase

3

Condition

Mood Disorders

Diabetes And Hypertension

Stress

Treatment

N/A

Clinical Study ID

NCT02519543
TRIO-BD-100
  • Ages > 18
  • All Genders

Study Summary

In a previous study by Dr. Calkin, the principal investigator of this study, persons with bipolar disorder and either type II diabetes or insulin resistance were found to experience more severe symptoms of bipolar illness and a lower response to treatment, compared to persons with bipolar disorder who did not have type II diabetes or insulin resistance. To further explore these findings, the investigators have developed this study to see if treating insulin resistance (using metformin, a drug used to improve the body's use of insulin) may also help improve the symptoms of bipolar illness.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. 18 years of age or older
  2. diagnosis of BD I or II
  3. non-remitting BD as defined by the presence of mood symptoms of at least moderateseverity, indicated by a MADRS score ≥ 15 despite being on optimal treatment accordingto the CANMAT/APA guidelines
  4. HOMA-IR ≥ 1.8, indicating IR (subjects will have FPG and FSI testing done to determinewhether they have IR or T2D)
  5. current episode of depression 4 weeks or longer in duration
  6. on a stable optimal dose of mood stabilizing treatment for at least 4 weeks prior tostudy entry

Exclusion

Exclusion Criteria:

  1. Diagnoses of organic mood disorder, mood disorder not otherwise specified, alcoholdependence, T1D or T2D
  2. presence of rapid cycling (by DSM-5 criteria), mania, (indicated by a Young ManiaRating Scale [YMRS] score > 15), or suicide ideation (current score of 5 on theSuicidal Ideation section of the Columbia-Suicide Severity Rating scale [C-SSRS])
  3. patient receiving metformin < 2 weeks prior to study entry
  4. metformin allergy or sensitivity
  5. metformin contraindicated where liver function tests > three times the upper limit ofnormal, estimated glomerular filtration rate (eGFR) < 30, CBC revealing megaloblasticanemia or pre-existing untreated B12 deficiency
  6. pregnancy or breastfeeding
  7. lactose intolerance, diagnosed by a physician
  8. chronic use of narcotic medications
  9. patient lacks full capacity to consent to study participation.

Study Design

Total Participants: 50
Study Start date:
September 01, 2015
Estimated Completion Date:
September 30, 2020

Study Description

This is a 26-week randomized, double-blind, parallel group prospective study of the effectiveness of treating insulin resistance (IR) to improve mood in patients with IR and treatment-resistant bipolar depression (TRBD). The investigators will compare the effects of treating IR (with metformin) versus placebo on outcome in each patient. The primary outcome will be change in Montgomery-Ǻsberg Depression Rating Scale (MADRS) scores. Patients' current optimized mood stabilizing treatment as usual (TAU, according to the Canadian Network for Mood and Anxiety Treatments [CANMAT] or American Psychiatric Association [APA] guidelines) must remain unchanged for a period of at least 4 weeks prior to and throughout the study. Patients will undergo a baseline assessment and then be randomized to treatment with metformin or placebo with titration to full dose after 2 weeks. Patients will remain on full treatment for 24 weeks thereafter (total trial duration of 26 weeks for each patient). In those patients with TRBD assigned to treatment with the insulin sensitizer metformin, a significant improvement in depression symptoms will be mediated by the conversion of IR to insulin sensitivity.

Subjects: We aim to enrol 110 subjects with IR and TRBD from 2 sites: the primary site in Halifax, Nova Scotia, Canada, and a second site in Pittsburgh, Pennsylvania, USA.

Connect with a study center

  • Nova Scotia Health Authority - Dept. of Psychiatry

    Halifax, Nova Scotia B3H 2E2
    Canada

    Site Not Available

  • Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh

    Pittsburgh, Pennsylvania 15213-2593
    United States

    Site Not Available

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