Metformin improves arterial stiffness in polycystic ovary syndrome (PCOS)
| ISRCTN | ISRCTN61785174 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN61785174 |
| Protocol serial number | Study Protocol Version 5 |
| Sponsor | Cardiff University (UK) |
| Funder | Royal College of Physicians (UK) - Lewis Thomas Gibbon Jenkins Fellowship |
- Submission date
- 08/04/2009
- Registration date
- 25/06/2009
- Last edited
- 05/08/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Aled Rees
Scientific
Scientific
Department of Endocrinology
University Hospital of Wales
Heath Park
Cardiff
CF144XW
United Kingdom
| Phone | +44 (0)2920 745 002 |
|---|---|
| reesda@cardiff.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomised double-blind placebo-controlled crossover trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | Metformin improves arterial stiffness and endothelial function in young women with polycystic ovary syndrome: a randomised crossover trial |
| Study objectives | To determine whether metformin therapy improves endothelial function and arterial compliance in young women with polycystic ovary syndrome (PCOS). |
| Ethics approval(s) | South Wales Research Ethics Committee approved in May 2006 (ref: 06/WSE04/33) |
| Health condition(s) or problem(s) studied | 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 / device / biological / vaccine name(s) | Metformin |
| Primary outcome measure(s) |
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. |
| Key secondary outcome measure(s) |
1. Changes in testosterone, plasminogen activator inhibitor-1 (PAI-1), endothelin-1 (ET-1) and high sensitivity C-reactive protein (hsCRP) |
| Completion date | 01/05/2008 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target sample size at registration | 32 |
| Key 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 |
| Key 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. |
| Date of first enrolment | 01/01/2007 |
| Date of final enrolment | 30/04/2008 |
Locations
Countries of recruitment
- United Kingdom
- Wales
Study participating centre
Department of Endocrinology
Cardiff
CF144XW
United Kingdom
CF144XW
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/02/2010 | Yes | No | |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
05/08/2019: The overall trial end date has been changed from 11/02/2008 to 01/05/2008.
24/07/2019: The overall trial end date has been changed from 30/04/2008 to 11/02/2008.
