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Trial registered on ANZCTR


Registration number
ACTRN12610000219088
Ethics application status
Approved
Date submitted
10/03/2010
Date registered
17/03/2010
Date last updated
2/11/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
The effects of metformin on the LKB1/AMP-activated protein kinase (AMPK) pathway in breast tissue, a pilot study
Scientific title
The effects of metformin on the LKB1/AMP-activated protein kinase (AMPK) pathway in breast tissue from women scheduled for reduction mammoplasty, a pilot study
Secondary ID [1] 1489 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
breast cancer 256931 0
Condition category
Condition code
Cancer 257074 257074 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
one week administration of oral metformin 500mg tablet (to minimize side effects) followed by one week of oral metformin 1000mg daily then 4 weeks administration of oral metformin 1500mg daily (3 x 500mg tablets)
Intervention code [1] 256121 0
Prevention
Intervention code [2] 256123 0
Treatment: Drugs
Comparator / control treatment
comparator group has no treatment
Control group
Active

Outcomes
Primary outcome [1] 257970 0
Change in LKB1 expression and activity. LKB1 messenger ribonucleic acid (mRNA) expression will be measured by real-time polymerase chain reaction (PCR) and Western Blot. LKB1 activity will be measured with a specific kinase assay (Merck)
Timepoint [1] 257970 0
4 weeks after dose of 1500mg metformin reached (starting dose is 1 week of 500mg daily)
Primary outcome [2] 258019 0
AMPK phosphorylation and cyclic adenosine monophosphate response element-binding (CREB)-regulated transcription coactivator (CRTC2) phosphorylation and translocation.
Total and phospho-AMPK will be determined by Western Blot analysis.
Total and phospho-CTRC2 will be determined by Western Blot analysis.
Immunochemistry will be conducted to ascertain the subcellular localization of the CTRC2
Timepoint [2] 258019 0
4 weeks after dose of 1500mg metformin reached (starting dose is 1 week of 500mg daily)
Primary outcome [3] 258020 0
Aromatase expression in breast tissue. this will be determined by qRT-PCR
Timepoint [3] 258020 0
4 weeks after dose of 1500mg metformin reached (starting dose is 1 week of 500mg daily)
Secondary outcome [1] 263504 0
no secondary outcomes
Timepoint [1] 263504 0
no secondary outcomes

Eligibility
Key inclusion criteria
Women
a) who are aged between 38 and 60 years
b) who are attending a breast surgeon and are scheduled to have a reduction mammoplasty
c) who have provided informed consent
Minimum age
38 Years
Maximum age
60 Years
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Women with any of the following:
a) Use of any systemic hormones in the last 6 months;
b) serious endocrine disorder with systemic disease;
c) alcohol consumption greater than 3 standard drinks per day;
d) known acute or chronic liver disease;
e) cardiac failure requiring medication
f) known renal disease
g) chronic hypoxic lung disease
e) type 2 or insulin dependent diabetes mellitus or use of an oral hypoglycemic agent.

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 1500mg of metformin daily or no treatment. Randomization will be stratified by body mass index( BMI) to ensure that the numbers of women with a body mass index (BMI) < 30 and those with a body mass index (BMI )> 30 are balanced in the two arms of the study. Two balanced randomization lists each containing 60 numbers have been generated for this study. List number 1 contains the numbers 1-60 (for women with a body mass index (BMI) <30) and list 2 the numbers 61-120 (for women with a body mass index (BMI) > 30). Participants who meet inclusion/exclusion criteria will be assigned a study number in consecutive order (a number between 1 and 60 for women with a body mass index (BMI) < 30 and numbers 61-120 for women with a body mass index ( BMI)>30). In order to maintain allocation concealment, a piece of paper with the group allocation (metformin or no treatment) 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 256624 0
University
Name [1] 256624 0
Monash University
Address [1] 256624 0
Monash University Wellington Rd Clayton VIC 3800
Country [1] 256624 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Monash University Wellington Rd Clayton VIC 3800
Country
Australia
Secondary sponsor category [1] 255913 0
None
Name [1] 255913 0
Address [1] 255913 0
Country [1] 255913 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258653 0
Monash University Human Research Ethics Committee (MUHREC)
Ethics committee address [1] 258653 0
Human Ethics Office
First Floor, Building 3e
Monash Research Office
Clayton Campus
Monash University VIC 3800
Ethics committee country [1] 258653 0
Australia
Date submitted for ethics approval [1] 258653 0
02/03/2010
Approval date [1] 258653 0
06/05/2010
Ethics approval number [1] 258653 0
2010000248

Summary
Brief summary
This study will investigate the effect of metformin on breast tissue in well women intending to undergo reduction mammoplasty. There is an interest in the possibility that metformin could decrease breast cancer incidence or cancer related deaths. Our proposed research is to examine the effects of metformin treatment on LKB1 expression and activity, AMPK phosphorylation and CRTC2 phosphorylation and translocation, as tissue in vivo and to explore relationships between identified cellular effects with serum indicators of insulin resistance.
Trial website
N/A
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30912 0
Prof Susan Davis
Address 30912 0
Women's Health Research Program Monash University Level 6, The Alfred Centre 99 Commercial Road Melbourne VIC 3004
Country 30912 0
Australia
Phone 30912 0
+61 3 9903 0827
Fax 30912 0
+61 3 9903 0828
Email 30912 0
susan.davis@monash.edu
Contact person for public queries
Name 14159 0
Prof Susan Davis
Address 14159 0
Women's Health Research Program Monash University Level 6, The Alfred Centre 99 Commercial Road Melbourne VIC 3004
Country 14159 0
Australia
Phone 14159 0
+61 3 9903 0827
Fax 14159 0
+61 3 9903 0828
Email 14159 0
susan.davis@monash.edu
Contact person for scientific queries
Name 5087 0
Prof Susan Davis
Address 5087 0
Women's Health Research Program Monash University Level 6, The Alfred Centre 99 Commercial Road Melbourne VIC 3004
Country 5087 0
Australia
Phone 5087 0
+61 3 9903 0827
Fax 5087 0
+61 3 9903 0828
Email 5087 0
susan.davis@monash.edu

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary