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Trial registered on ANZCTR


Registration number
ACTRN12610000836033
Ethics application status
Approved
Date submitted
16/07/2010
Date registered
6/10/2010
Date last updated
18/05/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Metformin for the management of insulin resistance in overweight women at midlife.
Scientific title
Metformin for the management of insulin resistance in overweight women at midlife.
Secondary ID [1] 252229 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
insulin resistance 257752 0
Condition category
Condition code
Metabolic and Endocrine 257928 257928 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
metformin hydrochloride, 850mg twice daily for 6 months, oral tablet
Intervention code [1] 256817 0
Treatment: Drugs
Intervention code [2] 257356 0
Prevention
Comparator / control treatment
placebo -- Sodium starch glycollate, maize starch, povidone, colloidal anhydrous silica, magnesium stearate, hypromellose, titanium dioxide, propylene glycol, Macrogol 6000 and purified talc.
1 tablet identical to metformin tablet taken twice daily for 6 months
Control group
Placebo

Outcomes
Primary outcome [1] 258791 0
Evaluation of the efficacy of metformin in mitigating the development of insulin resistance (IR) and diabetes in its preclinical phase in obese (body mass index (BMI) >30 and < 40 kg/m2 and waist circumference >88cm) euglycaemic-women in midlife. The primary outcome measurewill be change in IR determined by change in the homeostasis model of assessment (HOMA-IR).
Timepoint [1] 258791 0
after 6 months of treatment
Secondary outcome [1] 264856 0
change in fasting insulin measured by blood analysis
Timepoint [1] 264856 0
after 6 months of treatment
Secondary outcome [2] 265872 0
change in fasting glucose measure by blood analysis
Timepoint [2] 265872 0
after 6 months of treatment
Secondary outcome [3] 265873 0
change in BMI measured by weight on electronic scales
Timepoint [3] 265873 0
after 6 months of treatment
Secondary outcome [4] 265874 0
change waist circumference by tape measure
Timepoint [4] 265874 0
after 6 months oftreatment
Secondary outcome [5] 265875 0
change in lipid profile measure by blood analysis
Timepoint [5] 265875 0
after 6 months of treatment
Secondary outcome [6] 265876 0
change in sex hormone binding globulin measured by blood analysis
Timepoint [6] 265876 0
after 6 months of treatment
Secondary outcome [7] 265877 0
change in adiponectin levels measured by blood analysis
Timepoint [7] 265877 0
after 6 months of treatment
Secondary outcome [8] 265878 0
change in blood pressure measure by automatic sphymomanometer
Timepoint [8] 265878 0
after 6 months of treatment
Secondary outcome [9] 265879 0
change in soluble receptor for Advanced Glycation End product (sRAGE) measured by blood analysis
Timepoint [9] 265879 0
after 6 months of treatment
Secondary outcome [10] 265880 0
change in methylglyoxal measured by blood analysis
Timepoint [10] 265880 0
after 6 months of treatment
Secondary outcome [11] 265881 0
change in lactic acid measured by blood analysis
Timepoint [11] 265881 0
after 6 months of treatment
Secondary outcome [12] 265882 0
change in n-methylnicotinamide measured by blood analysis
Timepoint [12] 265882 0
after 6 months of treatment
Secondary outcome [13] 265883 0
change in fructose measured by blood analysis
Timepoint [13] 265883 0
after 6 months of treatment
Secondary outcome [14] 265884 0
change in urinary albumin-creatinine ratio measured by urine analysis
Timepoint [14] 265884 0
after 6 months of treatment
Secondary outcome [15] 265885 0
change in Haemaglobin A1c (HbA1c) measured by blood analysis
Timepoint [15] 265885 0
after 6 months of treatment

Eligibility
Key inclusion criteria
Women:1. who are aged between 35-65 years. 2. who have a BMI >30kg/m2 and <40kg/m2 and/or a waist circumference > 88cm. 3.who have provided informed consent.
Minimum age
35 Years
Maximum age
65 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Women with any of the following: (a) Use of testosterone, or dehydroepiandosterone (DHEA) in the last 3 months, or last 7 months in the case of hormonal implants (b) known severe psychiatric illness (c) uncontrolled hypertension, Systolic blood pressure (BP) > 160, Diastolic BP > 100 (d) pregnancy and lactation (e) serious endocrine disorder with systemic disease (f) alcohol consumption greater than 3 standard drinks per day (g) known acute or chronic liver disease (bilirubin > 26, alanine transferase > 100 U/L, alkaline phosphatase > 300 U/L) (h) Type 2 diabetes mellitus (T2DM), insulin dependent diabetes mellitus or use of an oral hypoglycemic agent (i) acute / chronic renal, liver, cardiovascular disease or any other chronic major illness which would impair overall health and wellbeing 2. Women who, in the opinion of the investigator, are a poor medical or psychiatric risk for treatment in a research protocol. 3. Women who have participated in a medical or surgical research protocol in the preceding 28 days.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Women will be randomized to receive either 850 mg metformin twice daily or identical placebo.

The investigators, study centre personnel and participants will remain blinded throughout the study.

In order to maintain allocation concealment, a piece of paper with the group allocation (metformin or placebo) assigned to each study number in the randomization list will be put into opaque envelopes numbered consecutively 1- 120. Randomization will occur when the envelope with the patient’s study number on it is opened.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
computer generated randomization code
Masking / blinding
Blinded (masking used)
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
Intervention assignment
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/11/2010
Actual
31/05/2011
Date of last participant enrolment
Anticipated
Actual
22/08/2012
Date of last data collection
Anticipated
Actual
Sample size
Target
124
Accrual to date
Final
100
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 257291 0
Charities/Societies/Foundations
Name [1] 257291 0
MBF Foundation
Country [1] 257291 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Monash University acting through its Department of Medicine Central Clinical School Wellington Road Clayton VIC 3800
Country
Australia
Secondary sponsor category [1] 256536 0
None
Name [1] 256536 0
Address [1] 256536 0
Country [1] 256536 0
Other collaborator category [1] 277726 0
Individual
Name [1] 277726 0
Professor Ric Day
University of New South Wales
Address [1] 277726 0
Department of Clinical Pharmacology and Toxicology
Therapeutics Centre, Level 2 Xavier Building
St Vincent's Hospital
Darlinghurst, NSW, 2010, Australia.
Country [1] 277726 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259317 0
Monash University Human Research Ethics Committee (MUHREC)
Ethics committee address [1] 259317 0
Human Ethics Office First Floor, Building 3e,
Monash Research Office.
Clayton Campus,
Wellington Rd,
Monash University
VIC 3800
Ethics committee country [1] 259317 0
Australia
Date submitted for ethics approval [1] 259317 0
Approval date [1] 259317 0
15/07/2010
Ethics approval number [1] 259317 0
CF10/1417 - 2010000757

Summary
Brief summary
Brief summary*

Abdominal weight gain and insulin resistance (IR) significantly increase the risk of some age related conditions in midlife women, namely cardiovascular disease, dementia and breast cancer. The aim of early intervention in individuals with abdominal obesity and IR when they are still euglycaemic is to prevent progression to type 2 diabetes mellitus and the development of other co-morbidities. We hypothesise that treatment of obese midlife euglycemic women with metformin will result in improved insulin sensitivity (assessed by homeostasis model of assessment (HOMA-IR) and increase in sex hormone binding globulin (SHBG)), weight loss, improved lipid parameters and an increase in adiponectin levels.
Trial website
Trial related presentations / publications
Roisin Worlsey, Robin J Bell, Penelope J Robinson, Fiona Jane, Susan R Davis
Metformin for the management of insulin resistance in overweight women at midlife. Abstract OC1. 14th World Congress on the Menopause Cancun May1-4, 2014
Worsley R, Jane F, Robinson PJ, Bell RJ, Davis SR. Metformin for overweight women at midlife: a double-blind, randomized, controlled trial. Climacteric. 2014 Oct 21:1-8
Public notes

Contacts
Principal investigator
Name 31400 0
Prof Susan Davis
Address 31400 0
Women's Health Research Program
Department of Epidemiology and Preventive Medicine
Monash University
Level 6, The Alfred Centre
99 Commercial Rd
Melbourne VIC 3004
Country 31400 0
Australia
Phone 31400 0
+61 3 9903 0827
Fax 31400 0
+61 3 9903 0828
Email 31400 0
[email protected]
Contact person for public queries
Name 14647 0
Prof Susan Davis
Address 14647 0
Women's Health Research Program
Department of Epidemiology and Preventive Medicine
Monash University
Level 6, The Alfred Centre
99 Commercial Rd
Melbourne VIC 3004
Country 14647 0
Australia
Phone 14647 0
+61 3 99030827
Fax 14647 0
+61 3 9903 0828
Email 14647 0
[email protected]
Contact person for scientific queries
Name 5575 0
Prof Susan Davis
Address 5575 0
Women's Health Research Program
Department of Epidemiology and Preventive Medicine
Monash University
Level 6, The Alfred Centre
99 Commercial Rd
Melbourne VIC 3004
Country 5575 0
Australia
Phone 5575 0
+61 3 99030827
Fax 5575 0
Email 5575 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIAbstracts of Oral Communications2014https://doi.org/10.3109/13697137.2014.893728
N.B. These documents automatically identified may not have been verified by the study sponsor.