ISRCTN - ISRCTN48560305: Do women with polycystic ovary syndrome have increased cardiovascular risk compared to normal controls and could this risk be reduced by liraglutide?

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

Study website

Contact information

Type

Scientific

Contact name

Prof Stephen Atkin

ORCID ID

Contact details

Head of Diabetes
Endocrinology and Metabolism
University of Hull
Brocklehurst building
Hull Royal Infirmary
Hull
HU3 2RW
United Kingdom
-
Stephen.Atkin@hyms.ac.uk

Additional identifiers

EudraCT/CTIS number

IRAS number

ClinicalTrials.gov number

Secondary identifying numbers

Protocol version 7

Study information

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?

Acronym

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

Study design

Open parallel single-centre trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Study setting(s)

Hospital

Study 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

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

Reason abandoned (if study stopped)

Eligibility

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 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 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

University of Hull
Hull
HU3 2RW
United Kingdom

Sponsor information

Organisation

Hull and East Yorkshire Hospitals NHS Trust (UK)

Sponsor type

Hospital/treatment centre

Website

http://www.hey.nhs.uk/

ROR

https://ror.org/01b11x021

Funders

Funder type

University/education

Funder name

University of Hull - Diabetes Research Fund (UK)

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

Individual participant data (IPD) Intention to share

No

IPD sharing plan

IPD sharing plan summary