Metformin improves arterial stiffness in polycystic ovary syndrome (PCOS)

ISRCTN	ISRCTN61785174
DOI	https://doi.org/10.1186/ISRCTN61785174
Secondary identifying numbers	Study Protocol Version 5

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

Department of Endocrinology
University Hospital of Wales
Heath Park
Cardiff
CF144XW
United Kingdom

Phone	+44 (0)2920 745 002
Email	reesda@cardiff.ac.uk

Study information

Study design	Randomised double-blind placebo-controlled crossover trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient 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
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Metformin
Primary outcome measure	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 study start date	01/01/2007
Completion date	01/05/2008

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Female
Target number of participants	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

Sponsor information

Cardiff University (UK)
University/education

c/o Chris Shaw
Research Governance Coordinator
Research And Commercial Division
30 - 36 Newport Road
Cardiff
CF24 0DE
Wales
United Kingdom

Email	shawc3@cardiff.ac.uk
Website	http://www.cardiff.ac.uk/
"ROR"	https://ror.org/03kk7td41

Funders

Funder type

University/education

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

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	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

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.