Diabetes Mellitus, Type 2Phase 4NCT02167620
Metformin in Co-morbid Diabetes or Prediabetes and Serious Mental Illness
A Phase 4 study testing Metformin in people with Diabetes Mellitus, Type 2 and Schizophrenia, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 17 to 45 years
- Conditions the study is for
- Diabetes Mellitus, Type 2, Schizophrenia
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 1 siteCanada
- Study dates
- Jun 2014to Mar 2018
- Phase
- Phase 4
- 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 17 to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
This is a 16 week, double-blind, randomized pilot study, which proposes to recruit 24 patients with schizophrenia, or schizoaffective disorders (DSM 5), who are overweight or obese (BMI >25) and have prediabetes or type 2 diabetes. Randomization occurs on a 2:1 basis, with 16 patients randomised to metformin, and 8 to placebo. Metfomin/placebo is dispensed monthly. The baseline and /or screening visit includes a physical exam (including anthropometric measures), medical history, fasting blood work (glucose, insulin, HbA1c, lipids, electrolytes, thyroid, liver/kidney function), in addition to a urine drug screen. Women of child-bearing age are given a pregnancy test. Patients who meet inclusion criteria and consent to the study have an oral glucose tolerance test (OGTT), and a baseline abdominal and brain MRI (to respectively assess visceral adiposity, a key risk factor for CV disease, and hippocampal volumes). Anthropometric measures and pill counts are repeated bi-weekly. At week 8, fasting insulin/glucose, HbA1C, and liver function tests are measured. End of study measures (week 16), include the same panel of bloodwork conducted at baseline, as well as a repeat OGTT, and an abdominal and brain MRI. Rountine psychopathology scales, including BPRS, CGI, and CDS will be measured at baseline, and week 16. The Brief Assessment of Cognition in Schizophrenia (BACS) will also be completed at baseline, and study end.
- Conditions
- Diabetes Mellitus, Type 2, Schizophrenia
- Being tested
- Metformin, Placebo
- Medical subject headings
- Diabetes Mellitus, Type 2, Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Metformin will be dispensed on a biweekly basis, and pill counts conducted at each visit.
PlaceboDrug
Also called Sugar pill
Placebo will be dispensed on a biweekly basis, and pill counts conducted at each visit.
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Placebo comparator | Metformin/ placebo will be dispensed on a biweekly basis, and pill counts conducted at each visit. Receives: Drug: Metformin |
| Placebo | Placebo comparator | Metformin/ placebo will be dispensed on a biweekly basis, and pill counts conducted at each visit. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 3 years
Secondary outcomes (5)
Decreases in visceral adiposity
Visceral adiposity assessment via MRI
Measured: 3 years
Decreases in hepatic adiposity
Hepatic adiposity assessment via MRI
Measured: 3 years
Greater than 5% decrease in body weight
Body weight assessment
Measured: 3 years
Improvements in cognition
Cognition assessment
Measured: 3 years
Improvements in hippocampal volume
Cognition assessment
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2014 (estimated)
- Study startJun 2014
- Primary completionFeb 2018
- Study completionMar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by Centre for Addiction and Mental HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Margaret Hahn, Centre for Addiction and Mental Health
- Investigators
- Margaret Hahn, Principal investigator, Center for Addiction and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02167620
- Sponsor's protocol ID
- 007/2014
- Status last verified
- Jul 2018
- First submitted
- 17 Jun 2014
- Last updated
- 30 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 33854039
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metformin in Co-morbid Diabetes or Prediabetes and Serious Mental Illness
- ClinicalTrials.gov ID
- NCT02167620
- Acronym / sponsor ID
- 007/2014
- Conditions
- Diabetes Mellitus, Type 2, Schizophrenia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Study start
- Jun 2014
- Primary completion
- Feb 2018 (actual)
- Study completion
- Mar 2018 (actual)
- First posted
- 19 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a 16 week, double-blind, randomized pilot study, which proposes to recruit 24 patients with schizophrenia, or schizoaffective disorders (DSM 5), who are overweight or obese (BMI >25) and have prediabetes or type 2 diabetes. Randomization occurs on a 2:1 basis, with 16 patients randomised to metformin, and 8 to placebo. Metfomin/placebo is dispensed monthly. The baseline and /or screening visit includes a physical exam (including anthropometric measures), medical history, fasting blood work (glucose, insulin, HbA1c, lipids, electrolytes, thyroid, liver/kidney function), in addition to a urine drug screen. Women of child-bearing age are given a pregnancy test. Patients who meet inclusion criteria and consent to the study have an oral glucose tolerance test (OGTT), and a baseline abdominal and brain MRI (to respectively assess visceral adiposity, a key risk factor for CV disease, and hippocampal volumes). Anthropometric measures and pill counts are repeated bi-weekly. At week 8, fasting insulin/glucose, HbA1C, and liver function tests are measured. End of study measures (week 16), include the same panel of bloodwork conducted at baseline, as well as a repeat OGTT, and an abdominal and brain MRI. Rountine psychopathology scales, including BPRS, CGI, and CDS will be measured at baseline, and week 16. The Brief Assessment of Cognition in Schizophrenia (BACS) will also be completed at baseline, and study end.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin | Placebo comparator | Drug: MetforminMetformin/ placebo will be dispensed on a biweekly basis, and pill counts conducted at each visit. |
| Placebo | Placebo comparator | Drug: PlaceboMetformin/ placebo will be dispensed on a biweekly basis, and pill counts conducted at each visit. |
Who may qualify
- Ages
- 17 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- 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)
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminMetformin will be dispensed on a biweekly basis, and pill counts conducted at each visit. | Drug | Metformin |
| PlaceboAlso: Sugar pillPlacebo will be dispensed on a biweekly basis, and pill counts conducted at each visit. | Drug | Placebo |
Primary outcome
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))
Time frame: 3 years
HbA1c value assessment
5 secondary outcomes
Decreases in visceral adiposity
Time frame: 3 years
Decreases in hepatic adiposity
Time frame: 3 years
Greater than 5% decrease in body weight
Time frame: 3 years
Improvements in cognition
Time frame: 3 years
Improvements in hippocampal volume
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2018.
- Derived from this study: PubMed 33854039Agarwal 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Margaret Hahn principal investigator
Center for Addiction and Mental Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metformin in people with Diabetes Mellitus, Type 2 and Schizophrenia, run by Centre for Addiction and Mental Health at 1 site in Canada.
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 2 inclusion and 6 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 30 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
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)) (time frame: 3 years). 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 NCT02167620, which also lists 1 linked publication.
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 30 Jul 2018.