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Trial registered on ANZCTR
Registration number
ACTRN12617001547336
Ethics application status
Approved
Date submitted
1/11/2017
Date registered
9/11/2017
Date last updated
15/10/2018
Type of registration
Prospectively registered
Titles & IDs
Public title
The efficacy of Metformin as an adjunctive treatment to attenuate weight gain and metabolic syndrome in patients with schizophrenia or schizoaffective disorder newly commenced on clozapine
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Scientific title
The efficacy of Metformin as an adjunctive treatment to attenuate weight gain and metabolic syndrome in patients with schizophrenia or schizoaffective disorder newly commenced on clozapine
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Secondary ID [1]
293257
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None
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Universal Trial Number (UTN)
U1111-1204-5601
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Trial acronym
Cadence CoMET
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Schizophrenia
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obesity
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metabolic syndrome
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schizoaffective disorder
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Condition category
Condition code
Mental Health
304609
304609
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0
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Schizophrenia
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Diet and Nutrition
304657
304657
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0
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Obesity
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Metabolic and Endocrine
304658
304658
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0
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Metabolic disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
The study will include 86 individuals with schizophrenia or schizoaffective disorder who
will be randomised to receive either 2g/d (2000 mg once daily) of Metformin XR tablet
or placebo (1:1 ratio) orally for 24 weeks, in addition to their normal
routine care.
Participants will be requested to return all unused study medication (i.e.
unopened bottles or tablets not taken) and empty bottles
to the delegated research assistants. All unused supplies of study
medication will be accounted for and documented by the designated
Research Pharmacist. Compliance with study medication will be
calculated at each visit by means of self-report and a tablet count.
Face to face clinical assessments will be weekly for the first 4 weeks and then monthly (4, 8, 12, 16, 20, 24) for the duration of the study.
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Intervention code [1]
299518
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Treatment: Drugs
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Comparator / control treatment
This study will use a placebo (microcrystalline cellulose gelatine capsules)
adjunct to routine care as a comparator condition.
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Control group
Placebo
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Outcomes
Primary outcome [1]
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Weight will be used as the primary outcome measure and will be conducted by research assistants using calibrated digital scales.
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Assessment method [1]
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Timepoint [1]
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24 weeks assessment
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Secondary outcome [1]
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Rate of conversion to T2DM. This will be defined from pathology results of fasting 2 hour glucose tolerance test and HbA1c)
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Assessment method [1]
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Timepoint [1]
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24 week assessment
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Secondary outcome [2]
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Metabolic syndrome will be assessed from pathology blood results
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Assessment method [2]
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Timepoint [2]
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24 weeks assessment
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Secondary outcome [3]
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Homeostatic model assessment (HOMA) of insulin resistance and secretion based on fasting glucose and insulin blood results
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Assessment method [3]
340260
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Timepoint [3]
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24 weeks assessment
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Secondary outcome [4]
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Metabolic bloods (glucagon)
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Assessment method [4]
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Timepoint [4]
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24 weeks assessment
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Secondary outcome [5]
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Diet and appetite (Food Craving Inventory)
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Assessment method [5]
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Timepoint [5]
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24 weeks assessment
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Secondary outcome [6]
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Liver function blood tests
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Assessment method [6]
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Timepoint [6]
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24 week assessment
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Eligibility
Key inclusion criteria
1. Aged between 18 and 64 years (inclusive)
2. Fulfil the DSM-IV criteria practice for schizophrenia or schizoaffective disorder, based on the Diagnostic Interview for Psychosis (DIP)
3. Have received oral clozapine for a period of no more than 2 weeks
4. Agree to participate, have capacity to consent and are able to follow the study instructions and procedures
5. Fasting Blood Glucose Level less than or equal to 5.6 mmols (confirmed within the previous two weeks of commencing clozapine)
6. BMI greater than or equal to 18 and less than or equal to 40
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Minimum age
18
Years
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Maximum age
64
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
1. Known allergies to Metformin or any part of the formulation of the investigational product
2. Obesity induced by other endocrinologic disorder (e.g Cushing Syndrome, untreated
Hypothyroidism)
3. Current use of any weight-lowering therapy including: pramlintide, sibutramine, orlistat, zonisamide, topiramate or phenteremine (either by prescription or as part of a clinical trial)
4. Diagnosis of Type 1 or Type 2 Diabetes mellitus or already on metformin
5. Participants treated with corticosteroids or other hormone therapy (except oestrogens or thyroxine) for greater than 10 days
6. Chronic kidney disease (eGFR<60mL/min)
7. Previous surgical treatment of obesity
8. BMI less than or equal to 18 or BMI greater than or equal to 40
9. Any concomitant disease or condition that according to the investigator’s assessment makes the patients unsuitable for trial participation
10. People who are unable to understand or communicate in English
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Eighty-six (86) participants will be recruited through the
mental health services in four Queensland Hospital and Health Services.
After verbal consent is provided, an assessment of inclusion/exclusion
criteria will commence. Participants who meet all inclusion criteria and
none of the exclusion criteria will be invited to participate in the study
and the formal consent process will commence. For those who consent
to participate, they will be enrolled in the study and randomized
according to allocation concealment methods.
Randomization lists will be created by an independent statistician, using
computerised methods and provided to the manufacturer. The
compounding manufacturer will develop the investigational product
according to the randomized list. The contracted Research Pharmacist will hold
the closed randomisation list and be the only one who has the ability to
unblind a participant. The Research Pharmacist will dispense the
investigational product based on the randomisation list provided. All
study personnel will be blinded to a participants’ drug group allocation (placebo versus active).
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be carried out using a computer-generated randomization table, Participants will receive either active treatment or placebo in a 1:1 ratio.
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 4
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Type of endpoint/s
Efficacy
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Statistical methods / analysis
We will adopt an intention-to-treat principle to analyse all outcomes (i.e. for those who do not complete the 24 week study period, we will carry forward their last observation on the study outcomes). For the primary outcome, we will be using repeated-measures ANCOVA analysis to assess for differences in the two group’s endpoint weight after adjusting for baseline weight. The significance level for the treatment effect will be set at the 0.05 level using two-sided test. For secondary outcome measures, we will be using paired t-test and Wilcoxon signed-rank tests to look at various metabolic syndrome components. We will also compare demographic and clinical differences between the groups at baseline using fisher exact or chi square test for categorical variables or two independent sample t-test for continuous variables.
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Recruitment
Recruitment status
Recruiting
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Date of first participant enrolment
Anticipated
8/01/2018
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Actual
5/03/2018
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Date of last participant enrolment
Anticipated
8/01/2021
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Actual
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Date of last data collection
Anticipated
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Actual
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Sample size
Target
86
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Accrual to date
9
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Final
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Recruitment in Australia
Recruitment state(s)
QLD
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Recruitment hospital [1]
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Royal Brisbane & Womens Hospital - Herston
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Recruitment hospital [2]
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Ipswich Hospital - Ipswich
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Recruitment hospital [3]
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The Prince Charles Hospital - Chermside
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Recruitment hospital [4]
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Logan Hospital - Meadowbrook
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Recruitment hospital [5]
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Redland Hospital - Cleveland
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Recruitment hospital [6]
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Caboolture Hospital - Caboolture
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Recruitment hospital [7]
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Princess Alexandra Hospital - Woolloongabba
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Recruitment postcode(s) [1]
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4029 - Herston
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Recruitment postcode(s) [2]
17986
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4305 - Ipswich
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Recruitment postcode(s) [3]
17987
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4032 - Chermside
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Recruitment postcode(s) [4]
17988
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4131 - Meadowbrook
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Recruitment postcode(s) [5]
17989
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4163 - Cleveland
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Recruitment postcode(s) [6]
17990
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4510 - Caboolture
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Recruitment postcode(s) [7]
17991
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4102 - Woolloongabba
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Funding & Sponsors
Funding source category [1]
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Government body
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Name [1]
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National Health and Medical Research Council (NHMRC)
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Address [1]
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Level 1
16 Marcus Clarke Street
Canberra ACT 2601
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Country [1]
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Australia
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Primary sponsor type
University
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Name
The University of Queensland
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Address
St Lucia, QLD 4072
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Country
Australia
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Secondary sponsor category [1]
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None
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Name [1]
296939
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Address [1]
296939
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Country [1]
296939
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Ethics approval
Ethics application status
Approved
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Ethics committee name [1]
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Metro South HREC (ECOO167)
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Ethics committee address [1]
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HREC Office – Centres for Health Research
Level 7
Translational Research Institute Building
Princess Alexandra Hospital
Ipswich Road
Woolloongabba QLD 4102
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Ethics committee country [1]
298935
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Australia
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Date submitted for ethics approval [1]
298935
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08/08/2017
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Approval date [1]
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12/10/2017
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Ethics approval number [1]
298935
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HREC/17/QPAH/538
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Summary
Brief summary
The study will be a randomised, placebo-controlled, double-blind parallelgroup
trial over a 24 week period. The primary objective is to examine the clinical efficacy of the add-on treatment of Metformin XR for people newly commenced on clozapine. Specifically, it is hypothesised, that participants allocated to the active arm (2000mg once daily) Metformin XR will have lower mean body weight at week 24 compared to individuals taking placebo, adjusted for baseline body weight (ANCOVA).
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Trial website
www.cadencetrials.com
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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A/Prof Dan Siskind
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Address
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Metro South Hospital and Health Service
Mobile Intensive Rehabilitation Team (MIRT)
228 Logan Road Woolloongabba QLD 4102
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Country
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Australia
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Phone
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+61 7 3317 1040
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Fax
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Email
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[email protected]
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Contact person for public queries
Name
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A/Prof Dan siskind
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Address
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Metro South Hospital and Health Service
Mobile Intensive Rehabilitation Team (MIRT)
228 Logan Road Woolloongabba QLD 4102
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Country
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Australia
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Phone
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+61 7 3317 1040
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Name
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A/Prof Dan siskind
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Address
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Metro South Hospital and Health Service
Mobile Intensive Rehabilitation Team (MIRT)
228 Logan Road Woolloongabba QLD 4102
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Country
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Australia
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Phone
78712
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+61 7 3317 1040
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Fax
78712
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Email
78712
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[email protected]
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No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Current supporting documents:
Updated to:
Doc. No.
Type
Citation
Link
Email
Other Details
Attachment
23572
Study protocol
373913-(Uploaded-16-03-2021-15-20-27)-Study-related document.docx
Results publications and other study-related documents
Documents added manually
No documents have been uploaded by study researchers.
Documents added automatically
Source
Title
Year of Publication
DOI
Embase
The potential effect of metformin on cognitive and other symptom dimensions in patients with schizophrenia and antipsychotic-induced weight gain: a systematic review, meta-analysis, and meta-regression.
2023
https://dx.doi.org/10.3389/fpsyt.2023.1215807
Embase
CoMET: a randomised controlled trial of co-commencement of metformin versus placebo as an adjunctive treatment to attenuate weight gain in patients with schizophrenia newly commenced on clozapine.
2021
https://dx.doi.org/10.1177/20451253211045248
Embase
CoMET: A protocol for a randomised controlled trial of co-commencement of METformin as an adjunctive treatment to attenuate weight gain and metabolic syndrome in patients with schizophrenia newly commenced on clozapine.
2018
https://dx.doi.org/10.1136/bmjopen-2017-021000
N.B. These documents automatically identified may not have been verified by the study sponsor.
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