Condition category
Nutritional, Metabolic, Endocrine
Date applied
08/04/2009
Date assigned
25/06/2009
Last edited
10/12/2009
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Aled Rees

ORCID ID

Contact details

Department of Endocrinology
University Hospital of Wales
Heath Park
Cardiff
CF144XW
United Kingdom
+44 (0)2920 745 002
reesda@cardiff.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Study Protocol Version 5

Study information

Scientific title

Metformin improves arterial stiffness and endothelial function in young women with polycystic ovary syndrome: a randomised crossover trial

Acronym

Study hypothesis

To determine whether metformin therapy improves endothelial function and arterial compliance in young women with polycystic ovary syndrome (PCOS).

Ethics approval

South Wales Research Ethics Committee approved in May 2006 (ref: 06/WSE04/33)

Study design

Randomised double-blind placebo-controlled crossover trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Polycystic ovary syndrome

Intervention

The two treatment arms are metformin and placebo. During the study phase, patients received consecutive daily doses of metformin for 12 weeks (84 days) followed by placebo or placebo followed by metformin, separated by an 8-week wash-out period. Metformin has a short circulatory half-life and 8-week washout intervals have been employed on this basis in previous studies. Metformin is used widely in treating anovulation associated with PCOS in doses of up to 2 g daily. The majority of patients tolerate treatment well though gastrointestinal side-effects are common initially and the doses of metformin were built up gradually in an attempt to minimise these (500 mg once daily for the first week, 500 mg twice daily for the second week then 500 mg three times daily thereafter).

The total duration of treatment was 32 weeks and the total duration of follow-up was also 32 weeks for both arms of this trial.

Intervention type

Drug

Phase

Not Applicable

Drug names

Metformin

Primary outcome measures

Changes in measures of arterial stiffness (pulse wave velocity and augmentation index as measured by pulse wave analysis post-salbutamol versus post-GTN) from baseline, recorded at enrolment and then repeated at 12 weeks, 20 weeks and 32 weeks.

Secondary outcome measures

1. Changes in testosterone, plasminogen activator inhibitor-1 (PAI-1), endothelin-1 (ET-1) and high sensitivity C-reactive protein (hsCRP)
2. Measures of insulin resistance
3. Lipid profile

Recorded at enrolment and then repeated at 12 weeks, 20 weeks and 32 weeks.

Overall trial start date

01/01/2007

Overall trial end date

30/04/2008

Reason abandoned

Eligibility

Participant inclusion criteria

1. From the Endocrinology clinics at the University Hospital of Wales
2. Diagnosed with PCOS, based on androgen excess (clinical symptoms of hyperandrogenism and/or elevated testosterone) with ovulatory dysfunction (fewer than six menstrual cycles per year), supported by ovarian ultrasound where available
3. Congenital adrenal hyperplasia, Cushings syndrome, androgen-secreting neoplasms, hyperprolactinaemia and thyroid disease excluded by biochemical testing
4. Aged between 18 and 35 years

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

32

Participant exclusion criteria

1. Pregnant
2. Breastfeeding
3. History of current or previous use (within 6 months) of oral contraceptives, anti-diabetics or anti-androgens
4. Contraindications to metformin therapy including renal or hepatic impairment, ketoacidosis, or conditions where tissue hypoxia is likely (e.g. sepsis, respiratory failure, recent myocardial infarction)
5. History of hypertension or diabetes
6. Able to use barrier methods of contraception if sexually active. In addition, pregnancy tests were performed at each study visit and patients were withdrawn from the study in the event of confirmed pregnancy.

Recruitment start date

01/01/2007

Recruitment end date

30/04/2008

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Department of Endocrinology
Cardiff
CF144XW
United Kingdom

Sponsor information

Organisation

Cardiff University (UK)

Sponsor details

c/o Chris Shaw
Research Governance Coordinator
Research And Commercial Division
30 - 36 Newport Road
Cardiff
CF24 0DE
United Kingdom
shawc3@cardiff.ac.uk

Sponsor type

University/education

Website

http://www.cardiff.ac.uk/

Funders

Funder type

University/education

Funder name

Royal College of Physicians (UK) - Lewis Thomas Gibbon Jenkins Fellowship

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19996308

Publication citations

  1. Results

    Agarwal N, Rice SP, Bolusani H, Luzio SD, Dunseath G, Ludgate M, Rees DA, Metformin reduces arterial stiffness and improves endothelial function in young women with polycystic ovary syndrome: a randomized, placebo-controlled, crossover trial., J. Clin. Endocrinol. Metab., 2010, 95, 2, 722-730, doi: 10.1210/jc.2009-1985.

Additional files

Editorial Notes