NCT02519543

Brief 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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Sep 2015

Longer than P75 for phase_3

Geographic Reach
2 countries

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 3, 2015

Completed
8 days until next milestone

First Posted

Study publicly available on registry

August 11, 2015

Completed
21 days until next milestone

Study Start

First participant enrolled

September 1, 2015

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2020

Completed
Last Updated

January 13, 2021

Status Verified

January 1, 2021

Enrollment Period

5 years

First QC Date

August 3, 2015

Last Update Submit

January 12, 2021

Conditions

Bipolar Disorder

Keywords

insulin resistance

Outcome Measures

Primary Outcomes (1)

  • Montgomery-Ǻsberg Depression Rating Scale (MADRS)

    Using this scale, we will study the effect of treating insulin resistance (IR) on bipolar depression symptoms after 14 weeks of study drug treatment. We will assess whether the effect of metformin on improvement in MADRS scores at week 14 is mediated by conversion of IR to insulin sensitivity (determined using Homeostatic Model Assessment - Insulin Resistance, i.e. HOMA-IR).

    14 weeks

Secondary Outcomes (7)

  • Montgomery-Ǻsberg Depression Rating Scale (MADRS)

    26 weeks

  • Montgomery-Ǻsberg Depression Rating Scale (MADRS)

    14 and 26 weeks

  • Inventory of Depressive Symptomatology-Self Rating (IDS-SR)

    14 and 26 weeks

  • Young Mania Rating Scale (YMRS)

    14 and 26 weeks

  • Hamilton Anxiety Rating Scale (HAM-A)

    14 and 26 weeks

  • +2 more secondary outcomes

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo comparator to be given twice daily, once with breakfast and once with supper

Drug: Placebo

Metformin

EXPERIMENTAL

Metformin 2000 mg daily to be given as follows: 1000 mg with breakfast and 1000 mg with supper

Drug: Metformin

Interventions

PlaceboDRUG

Placebo to be given twice daily, once with breakfast and once with supper

Also known as: sugar pill
Placebo
MetforminDRUG

Active experimental drug to be given twice a day, 1000 mg with breakfast and 1000 mg with supper

Also known as: Metformin Hydrochloride
Metformin

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • years of age or older
  • diagnosis of BD I or II
  • non-remitting BD as defined by the presence of mood symptoms of at least moderate severity, indicated by a MADRS score ≥ 15 despite being on optimal treatment according to the CANMAT/APA guidelines
  • HOMA-IR ≥ 1.8, indicating IR (subjects will have FPG and FSI testing done to determine whether they have IR or T2D)
  • current episode of depression 4 weeks or longer in duration
  • on a stable optimal dose of mood stabilizing treatment for at least 4 weeks prior to study entry

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

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

Pittsburgh, Pennsylvania, 15213-2593, United States

Location

Nova Scotia Health Authority - Dept. of Psychiatry

Halifax, Nova Scotia, B3H 2E2, Canada

Location

Related Publications (4)

  • Calkin CV, Ruzickova M, Uher R, Hajek T, Slaney CM, Garnham JS, O'Donovan MC, Alda M. Insulin resistance and outcome in bipolar disorder. Br J Psychiatry. 2015 Jan;206(1):52-7. doi: 10.1192/bjp.bp.114.152850. Epub 2014 Oct 16.

    PMID: 25323142BACKGROUND

  • Ruzickova M, Slaney C, Garnham J, Alda M. Clinical features of bipolar disorder with and without comorbid diabetes mellitus. Can J Psychiatry. 2003 Aug;48(7):458-61. doi: 10.1177/070674370304800705.

    PMID: 12971015BACKGROUND

  • Calkin CV, Gardner DM, Ransom T, Alda M. The relationship between bipolar disorder and type 2 diabetes: more than just co-morbid disorders. Ann Med. 2013 Mar;45(2):171-81. doi: 10.3109/07853890.2012.687835. Epub 2012 May 24.

    PMID: 22621171BACKGROUND

  • Calkin CV, Chengappa KNR, Cairns K, Cookey J, Gannon J, Alda M, O'Donovan C, Reardon C, Sanches M, Ruzickova M. Treating Insulin Resistance With Metformin as a Strategy to Improve Clinical Outcomes in Treatment-Resistant Bipolar Depression (the TRIO-BD Study): A Randomized, Quadruple-Masked, Placebo-Controlled Clinical Trial. J Clin Psychiatry. 2022 Feb 1;83(2):21m14022. doi: 10.4088/JCP.21m14022.

    PMID: 35120288DERIVED

Related Links

MeSH Terms

Conditions

Bipolar DisorderInsulin Resistance

Interventions

SugarsMetformin

Condition Hierarchy (Ancestors)

Bipolar and Related DisordersMood DisordersMental DisordersHyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

CarbohydratesBiguanidesGuanidinesAmidinesOrganic Chemicals

Study Officials

  • Cynthia Calkin, MD FRCPC

    Nova Scotia Health Authority

    PRINCIPAL INVESTIGATOR

  • Roy Chengappa, MD FRCPC

    Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Cynthia Calkin, Associate Professor, Dalhousie University, Nova Scotia Health Authority

Study Record Dates

First Submitted

August 3, 2015

First Posted

August 11, 2015

Study Start

September 1, 2015

Primary Completion

September 1, 2020

Study Completion

September 1, 2020

Last Updated

January 13, 2021

Record last verified: 2021-01

Data Sharing

IPD Sharing
Will not share

Locations

US(1)CA(1)