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Bipolar DisorderPhase 3TRIO-BDNCT02519543

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

A Phase 3 study testing Metformin in people with Bipolar Disorder, run by Cynthia Calkin at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Bipolar Disorder
What is being tested?
Metformin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
50 participants
Where
2 sitesin 2 countries
Study dates
Sep 2015to Sep 2020
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 18 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

Who cannot join

  • 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
Show all 9Show fewer
  • lactose intolerance, diagnosed by a physician
  • chronic use of narcotic medications
  • patient lacks full capacity to consent to study participation.

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

United States1 site

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

    Pittsburgh, Pennsylvania, 15213-2593

Other trials in United States

Canada1 site

  • Nova Scotia Health Authority - Dept. of Psychiatry

    Halifax, Nova Scotia, B3H 2E2

Other trials in Canada

About this study

Official title: Treating Insulin Resistance to Improve Outcome in Refractory Bipolar Disorder: a Randomized, Double-blind, Placebo-control Study of the Efficacy of Metformin in Patients With Insulin Resistance and Non-remitting Bipolar Illness

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.

Read the detailed 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.

Being tested
Placebo, Metformin
Keywords
insulin resistance
Medical subject headings
Bipolar Disorder, Insulin Resistance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboDrug

    Also called sugar pill

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

  • MetforminDrug

    Also called Metformin Hydrochloride

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

Study groups in NCT02519543
Study groupRoleWhat they receive
PlaceboPlacebo comparatorPlacebo comparator to be given twice daily, once with breakfast and once with supper
Receives: Drug: Placebo
MetforminExperimentalMetformin 2000 mg daily to be given as follows: 1000 mg with breakfast and 1000 mg with supper
Receives: Drug: Metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: 14 weeks

Secondary outcomes (7)

  1. Montgomery-Ǻsberg Depression Rating Scale (MADRS)

    Using this scale, we will assess whether the effect of treating IR on bipolar depression symptoms is sustained up to 26 weeks.

    Measured: 26 weeks

  2. Montgomery-Ǻsberg Depression Rating Scale (MADRS)

    Using this scale, we will assess whether treating IR results in a ≥ 30% improvement in bipolar depression symptoms after 14 weeks and 26 weeks of study drug treatment.

    Measured: 14 and 26 weeks

  3. Inventory of Depressive Symptomatology-Self Rating (IDS-SR)

    We will examine the effect of treating IR on mood and anxiety symptoms using this rating scale.

    Measured: 14 and 26 weeks

  4. Young Mania Rating Scale (YMRS)

    We will examine the effect of treating IR on mania symptoms using this rating scale.

    Measured: 14 and 26 weeks

  5. Hamilton Anxiety Rating Scale (HAM-A)

    We will examine the effect of treating IR on mood and anxiety symptoms using this rating scale.

    Measured: 14 and 26 weeks

  6. Clinical Global Impression modified for use in Bipolar Disorder (CGI-BP)

    We will use this scale to assess the effect of treating IR on overall psychiatric morbidity and severity of illness.

    Measured: 14 and 26 weeks

  7. Global Assessment of Functioning (GAF)

    We will use this scale to assess the effect of treating IR on overall psychiatric morbidity and severity of illness.

    Measured: 14 and 26 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Aug 2015 (estimated)
  2. Study startSep 2015
  3. Primary completionSep 2020
  4. Study completionSep 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02519543
Sponsor's protocol ID
TRIO-BD-100
Acronym
TRIO-BD
Status last verified
Jan 2021
First submitted
3 Aug 2015
Last updated
13 Jan 2021
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 25323142

  • 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.

    PubMed 12971015

  • 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.

    PubMed 22621171

  • 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.

    PubMed 35120288

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Metformin in people with Bipolar Disorder, run by Cynthia Calkin at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Montgomery-Ǻsberg Depression Rating Scale (MADRS) (time frame: 14 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02519543, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2021.

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