Metformin in Co-morbid Diabetes or Prediabetes and Serious Mental Illness

NCT02167620 | Completed Phase 4 DMC

• 1 other identifier: 007/2014
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Schizophrenia is associated with a lifespan shortened by 20 years, due to cardiovascular disease (CVD), with antipsychotic (AP) medications understood to contribute to this risk through associated metabolic side-effects. Metformin, a medication used to treat prediabetes, and diabetes in the general population, holds promise with regard to reduction of AP-related metabolic problems, but has not been directly tested in early episode patients beyond weight loss, nor specifically in patients with diabetes or prediabetes and psychosis. We propose to replicate findings that metformin can reduce weight gain, and dysglycemia uniquely focusing on an early episode population diagnosed with prediabetes or diabetes. To help determine long-term risk/benefit of adjunctive metformin, we propose to look at changes in abdominal and liver fat, two well-established risk factors for CVD. Given links between dysglycemia, obesity with hippocampal volume loss and cognitive dysfunction, we will explore if improvements in metabolic indices are associated in changes in cognition and brain structure.

Conditions

Diabetes Mellitus, Type 2; Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Improvement in HbA1C derived from Oral glucose tolerance test (Matsuda, index of insulin sensitivity; area under glucose curve; insulin secretion sensitivity index-2 (ISSI-2))

  HbA1c value assessment

  3 years

Secondary Outcomes (5)

• Decreases in visceral adiposity

  3 years

• Decreases in hepatic adiposity

  3 years

• Greater than 5% decrease in body weight

  3 years

• Improvements in cognition

  3 years

• Improvements in hippocampal volume

  3 years

Study Arms (2)

Metformin

PLACEBO COMPARATOR

Metformin/ placebo will be dispensed on a biweekly basis, and pill counts conducted at each visit.

Drug: Metformin

Placebo

PLACEBO COMPARATOR

Metformin/ placebo will be dispensed on a biweekly basis, and pill counts conducted at each visit.

Drug: Placebo

Interventions

Metformin DRUG

Metformin will be dispensed on a biweekly basis, and pill counts conducted at each visit.

Metformin

Placebo DRUG

Placebo will be dispensed on a biweekly basis, and pill counts conducted at each visit.

Also known as: Sugar pill

Placebo

Eligibility Criteria

• Age: 17 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients within 5 years of diagnosis of schizophrenia, schizoaffective disorder , or bipolar disorder(DSM V), or those younger than 40 years old, regardless of duration of illness
• Co-morbid diagnosis of prediabetes or diabetes (Canadian or American Diabetes Association criteria)

You may not qualify if:

• Patients with co-morbid axis, other than nicotine dependence, or cannabis abuse
• Patients with liver, or renal dysfunction,
• Patients with a positive drug urine screen (other than cannabis or nicotine)
• Females with a positive pregnancy test will be excluded.
• Prior trial with metformin, and reported lack of tolerability
• Patients with an A1C \> 9.5%, or symptomatic hyperglycemia with metabolic decompensation

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead

Study Sites (1)

Center for Addiction and Mental Health

Toronto, Ontario, Canada

Location

Related Publications (1)

• Agarwal SM, Panda R, Costa-Dookhan KA, MacKenzie NE, Treen QC, Caravaggio F, Hashim E, Leung G, Kirpalani A, Matheson K, Chintoh AF, Kramer CK, Voineskos AN, Graff-Guerrero A, Remington GJ, Hahn MK. Metformin for early comorbid glucose dysregulation and schizophrenia spectrum disorders: a pilot double-blind randomized clinical trial. Transl Psychiatry. 2021 Apr 14;11(1):219. doi: 10.1038/s41398-021-01338-2.

  PMID: 33854039 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Schizophrenia

Interventions

Metformin; Sugars

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Carbohydrates

Study Officials

• Margaret Hahn

  Center for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinician/Scientist

Study Record Dates

• First Submitted: June 17, 2014
• First Posted: June 19, 2014
• Study Start: June 1, 2014
• Primary Completion: February 1, 2018
• Study Completion: March 1, 2018
• Last Updated: July 30, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)