The effects of metformin on the LKB1/AMP-activated protein kinase (AMPK) pathway in breast tissue, a pilot study

• Register: ANZCTR
• Last refreshed on: 13 January 2020
• Main ID: ACTRN12610000219088
• Date of registration: 17/03/2010
• Prospective Registration: Yes
• Primary sponsor: Monash University
• 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
• Date of first enrolment: 24/05/2011
• Target sample size: 20
• Recruitment status: Stopped early
• URL: https://anzctr.org.au/ACTRN12610000219088.aspx
• Study type: Interventional
• Study design: Purpose: Prevention; Allocation: Randomised controlled trial; Masking: Open (masking not used);Assignment: Parallel;Type of endpoint: Pharmacodynamics;
• Phase: Phase 4

Countries of recruitment

Australia

Contacts

• Name: Prof Susan Davis

• Name: Prof Susan Davis

Key inclusion & exclusion criteria

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
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.

Age minimum: 38 Years
Age maximum: 60 Years
Gender: Females

Health Condition(s) or Problem(s) studied

Cancer - Breast

breast cancer;
breast cancer

Intervention(s)

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)

Primary Outcome(s)

Aromatase expression in breast tissue. this will be determined by qRT-PCR[4 weeks after dose of 1500mg metformin reached (starting dose is 1 week of 500mg daily)]

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)[4 weeks after dose of 1500mg metformin reached (starting dose is 1 week of 500mg daily)]

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[4 weeks after dose of 1500mg metformin reached (starting dose is 1 week of 500mg daily)]

Secondary Outcome(s)

no secondary outcomes[no secondary outcomes]

Secondary ID(s)

none

Source(s) of Monetary Support

Monash University

Ethics review

Status: Approved
Approval date:
Contact:

Monash University Human Research Ethics Committee (MUHREC)