Do women with polycystic ovary syndrome have increased cardiovascular risk compared to normal controls and could this risk be reduced by liraglutide?
| ISRCTN | ISRCTN48560305 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN48560305 |
| Secondary identifying numbers | Protocol version 7 |
- Submission date
- 08/05/2012
- Registration date
- 22/05/2012
- Last edited
- 02/10/2015
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English Summary
Background and study aims:
Polycystic ovary syndrome (PCOS) is a common condition in women of reproductive age. PCOS is associated with cardiovascular risk through increased insulin resistance. This in turn may lead to increased risk of non-alcoholic fatty liver disease (NAFLD). Both conditions are made worse by obesity. Liraglutide has been shown to reduce weight, but it is unknown if liraglutide improves cardiovascular risk factors in women with PCOS with or without NALFD.
Who can participate?
Two groups of women: 20 with PCOS; 20 age and weight matched normal control subjects.
What does the study involve?
Participants are treated with liraglutide 1.8mg once a day for 6 months followed by metformin 500mg three times a day for 3 months. Study participants will be seen every 3 months. At each visit blood will be taken to measure for insulin resistance, and for clotting and inflammations markers. Artery wall thickness will be measured at baseline and after 6 months treatment with liraglutide.
What are the possible benefits and risks of participating?
There will be no immediate direct benefit to those taking part but the study will improve our understanding of PCOS and the treatment of people with PCOS and fatty liver disease. Most common side effects with metformin and liraglutide use are nausea and diarrhoea. These side effects usually disappear after a few days. There might be some discomfort in blood testing and endothelial function measurement.
Where is the study run from?
Diabetes Research Centre at Hull Royal Infirmary (UK).
When is the study starting and how long is it expected to run for?
May 2010 to December 2012.
Who is funding the study?
Diabetes Research fund, University of Hull (UK).
Who is the main contact?
Professor Stephen L Atkin
Stephen.atkin@hyms.ac.uk
Contact information
Scientific
Head of Diabetes, Endocrinology and Metabolism
University of Hull
Brocklehurst building
Hull Royal Infirmary
Hull
HU3 2RW
United Kingdom
| Stephen.Atkin@hyms.ac.uk |
Study information
| Study design | Open parallel single-centre 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 | Are early and late cardiovascular risk markers in women with polycystic ovary syndrome increased with concomitant non-alcoholic steatohepatitis and can this be modified with liraglutide? |
| Study hypothesis | Intervention with liraglutide significantly improves insulin resistance, carotid intima-media wall thickness (cIMT), platelet and endothelial function in women with PCOS and Non-alcoholic fatty liver disease (NAFLD). |
| Ethics approval(s) | Leeds East Research Ethics Committee, 08/02/2010 |
| Condition | Polycystic Ovary Syndrome |
| Intervention | Women with PCOS were diagnosed according to the Rotterdam criteria. Other endocrine disorders with similar presentation were excluded. Normal control women underwent similar tests to rule out any unknown medical problem. Participants (PCOS and nomal controls) are treated with liraglutide 1.8mg once a day for 6 months followed by metformin 500mg three times a day for 3 months. Study participants will be seen every 3 months during the study. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Liraglutide, metformin |
| Primary outcome measure | Improvement in cIMT and platelet function measured at baseline and after 6 months treatment with Liraglutide |
| Secondary outcome measures | 1. Improvement in endothelial function will be measured using EndoPat 2000 at baseline, 3, 6 and 9 months of treatment 2. Liver fibrosis markers were measured at baseline, 3, 6 and 9months of treatment 3. Depression [Centre for Epidemiologic Studies Depression Scale (CES-D)] at baseline and after 6 months of treatment with liraglutide 4. Quality of life will be measured using WHO QoL questionaire at baseline and after 6 months of treatment with liraglutide |
| Overall study start date | 24/05/2010 |
| Overall study end date | 31/12/2012 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 45 Years |
| Sex | Female |
| Target number of participants | 40 participants |
| Participant inclusion criteria | For PCOS: Polycystic ovary syndrome (defined by the Rotterdam criteria) as 2 out of 3 of: 1. Oligo / anovulation 2. Clinical or biochemical evidence of hirsuitism, and/or 3. Polycystic ovaries on ultrasound and the exclusion of other disorders 4. Age 18-45 years For normal controls: 1. Female, aged 18 - 45 2. Body madd index (BMI) 30 - 45 3. No current medical problems |
| Participant exclusion criteria | 1. Ketoacidosis 2. Severe gastrointestinal disease 3. Hypothyroidism 4. Subjects taking regular medications associated with high risk of hepatotoxicity like isoniazid and methotrexate 5. Not using a reliable method of contraception 6. Patients not allowing disclosure to their GP's 7. History of pancreatitis 8. Heart Failure 9. Chronic renal failure (creatinine clearance less than 60 ml/min or plasma creatinine >150 umol/L) 10. Pregnancy or breastfeeding women 11. Liver function tests >300% reference range normal (eg ALT>90 u/mL) 12. Type 2 diabetes mellitus 13. Acute conditions with the potential to alter renal function such as: dehydration / severe infection / shock / intravascular administration of iodinated contrast |
| Recruitment start date | 24/05/2010 |
| Recruitment end date | 31/12/2012 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
HU3 2RW
United Kingdom
Sponsor information
Hospital/treatment centre
c/o James Illingworth
Research and Development
Daisy Building
Castle Hill Hospital
Castle Road
Cottingham
Hull
HU16 5JQ
England
United Kingdom
| James.Illingworth@hey.nhs.uk | |
| Website | http://www.hey.nhs.uk/ |
"ROR" |
https://ror.org/01b11x021 |
Funders
Funder type
University/education
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 | 02/04/2015 | Yes | No |
