A trial of 26 weeks of subcutaneous liraglutide (a GLP1 receptor agonist), with or without continuous positive airway pressure (CPAP), in patients with type 2 diabetes mellitus (T2DM) and obstructive sleep apnoea (OSA)
| ISRCTN | ISRCTN16250774 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16250774 |
| Secondary identifying numbers | 19540 |
- Submission date
- 19/08/2015
- Registration date
- 19/08/2015
- Last edited
- 11/12/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Plain English Summary
Background and study aims
Obstructive sleep apnoea (OSA) is a condition where there is repeated closing of the upper airway during sleep. It can cause snoring, waking during sleep and periods of not being able to breathe. People who are obese with type 2 diabetes mellitus (T2DM) are at particularly high risk of developing OSA; approximately 86% have the condition. If not given effective treatment OSA can lead to long-term health issues. Current treatment options for OSA include losing weight (via either a very low energy diet, intensive lifestyle changes or metabolic surgery) or, in the absence of weight loss, a continuous positive airway pressure (CPAP) device that prevent the airway closing while the patient is asleep. However, compliance with these treatments is poor. Glucagonlike peptide receptor agonist (GLP1RA) therapy is commonly used in the treatment of diabetes. This drug has been shown to improve obesity and insulin resistance. To date, there have been no studies to examine the effects of GLP1RA on OSA in patients with T2DM. This study will examine the effectiveness of 26 weeks of GLP1RA, with and without CPAP, in obese patients with OSA and T2DM.
Who can participate?
Adults aged 18-75 with OSA and T2DM
What does the study involve?
Patients first have a series of physiological assessments to examine metabolic and cardiovascular (for example heart) health. They are then randomly allocated into one of 4 groups and treated accordingly: control (no treatment), GLP1RA, CPAP, and finally GLP1RA and CPAP. All assessments are repeated after the study period of 26 weeks.
What are the possible benefits and risks of participating?
Not provided at time of registration.
Where is the study run from?
GP and outpatients clinics across the Liverpool and Newcastle areas (UK)
When is the study starting and how long is it expected to run for?
September 2015 to October 2019
Who is funding the study?
Novo Nordisk UK Research Foundation
Who is the main contact?
Kellie Platt
Kellie.Platt@liverpool.ac.uk
Contact information
Public
Liverpool Clinical Trials Centre (LCTC)
University of Liverpool
Block C, 1st Floor
Waterhouse Building
1-3 Brownlow Street
Liverpool
L69 3GL
United Kingdom
| Phone | +44 (0)151 794 8897 |
|---|---|
| Kellie.Platt@liverpool.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | A randomised, controlled multi-centre trial of 26 weeks of subcutaneous liraglutide (a GLP1 receptor agonist), with or without continuous positive airway pressure (CPAP), in patients with type 2 diabetes mellitus (T2DM) and obstructive sleep apnoea (OSA) |
| Study acronym | ROMANCE |
| Study hypothesis | The aim of this study is to examine the efficacy of 26 weeks of glucagon-like peptide receptor agonist (GLP1RA) therapy , with and without continuous positive airway pressure (CPAP) treatment in obese patients with obstructive sleep apnoea (OSA) and type 2 diabetes mellitus (T2DM). |
| Ethics approval(s) | 14/NW/1019 |
| Condition | Diabetes, sleep apnoea |
| Intervention | Following screening, patients with OSA and T2DM will be recruited from primary (GPs) and secondary care settings (outpatients clinics) across the Liverpool and Newcastle areas. After informed consent has been obtained patients will undergo a series of physiological assessments to examine metabolic and cardiovascular health and will then randomised to one of the following interventions: 1. Control (no intervention) 2. GLP1RA 3. CPAP 4. GLP1RA & CPAP All assessments will be repeated following the intervention period. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III/IV |
| Drug / device / biological / vaccine name(s) | Liraglutide |
| Primary outcome measure | Liraglutide treatment |
| Secondary outcome measures | N/A |
| Overall study start date | 01/09/2015 |
| Overall study end date | 10/10/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 152; UK Sample Size: 152 |
| Participant inclusion criteria | 1. Males or females, age 18-75 years 2. Reproductive Status: Definition of Women of Child Bearing Potential (WOCBP). WOCBP comprises women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who are not postmenopausal (see definition below) 3. WOCBP must have a negative serum or urine pregnancy test result (minimum sensitivity 25 IU/L or equivalent units of HCG) within 0 to 72 hours before the first dose of study drug. 4. A clinical diagnosis of type 2 diabetes 5. Glycosylated haemoglobin (HbA1c) >53mmol/mol 6. BMI>30kg/ m2 7. Currently treated with either diet or any combination of metformin and sulphonylureas (excluding patients treated with DPPIV inhibitors*, pioglitazone or insulin) 8. No current use of Liraglutide treatment 9. Patients with moderatesevere OSA as assessed by polysomnographic criteria, either by: 9.1. Apnoeahypopnea index (AHI) >15 events/hour) with overnight domiciliary multichannel sleep study (ResMed, Apnoea Link™ or other suitable alternative) 9.2. Overnight desaturation index (pulse oximetry): ODI>10 (4% dip in oxygen saturation more than 10 events/hour) 9.3. Currently symptomatic for OSA, with excessive daytime sleepiness *Patients who are currently treated with DPPIV inhibitors can be included providing the treatment is discontinued before baseline tests. |
| Participant exclusion criteria | 1. Medical History and Concurrent Diseases 2. Females of childbearing age who are not using adequate contraceptive methods or who are planning a pregnancy in the next 6 months 3. Treatment with DPP-IV inhibitors, pioglitazone or subcutaneous insulin injections or with the antiobesity medication, orlistat 4. Patients in whom there may be occupational implications to a diagnosis of OSA e.g. professional drivers or operating machinery 5. Type 1 diabetes mellitus 6. Congestive heart failure class IIIIV 7. Renal impairment: eGFR less than 30 ml/minute/1.73m2 8. Previous history of acute pancreatitis 9. Hyperthyroidism 10. Hypothyroidism (subjects with a normal TSH and free T4, and on a stable dose of thyroxine for at least 3 months may be included) 11. Uncontrolled hypertension (blood pressure >170/120 mmHg) 12. Recent (< 6 months) myocardial infarction 13. Previous stroke (with residual neurological deficit) 14. Significant cardiac dysrhythmias (including pacemaker or ICD) 15. Presence of any other medical condition that would, in the opinion of the investigator or their clinician preclude safe participation in the study. This decision should be informed by Liraglutide precautions for use statements which will be provided to all clinicians and the research team 16. Alcohol consumption in excess of daily recommended limits (21 units/week females, 28 units/week males) 17. Any history of internal metal, pacemakers, or ferromagnetic metallic implants intraocular foreign bodies or cerebral aneurysm clips (exclusion from MR scanning) 18. History of seizures or unexplained syncope 19. Severe sleepiness 20. Weight <140kg (due to limitations of MRI scanner) 21. Subjects with a history of any serious hypersensitivity reaction to GLP1RA 22. WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the study duration plus 8 weeks after the last dose of study drug in such a manner that the risk of pregnancy is minimized 23. Women who are pregnant or breastfeeding 24. Diabetes treated with pioglitazone, GLP1 analogues or insulin 25. Use of other weight loss medication or any drug that might affect body weight or appetite (including antidepressants, antipsychotics, corticosteroids) 26. Prisoners or subjects who are involuntarily incarcerated 27. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness |
| Recruitment start date | 01/09/2015 |
| Recruitment end date | 01/10/2017 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
1-3 Brownlow Street
Liverpool
L69 3GL
United Kingdom
Sponsor information
University/education
Department of Neurological Science
Clinical Sciences Centre
Lower Lane
Fazakerley
Liverpool
L9 7LJ
England
United Kingdom
| Website | http://www.liv.ac.uk/ |
|---|---|
"ROR" |
https://ror.org/04xs57h96 |
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- The Novo Nordisk UK Research Foundation, ovo Nordisk Research Foundation UK, NNUKRF
- Location
- United Kingdom
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? |
|---|---|---|---|---|---|
| Protocol article | protocol | 22/07/2020 | 11/12/2020 | Yes | No |
| HRA research summary | 26/07/2023 | No | No |
Editorial Notes
11/12/2020: Publication reference added.
03/09/2020: Contact details updated.
28/08/2020: The overall trial end date was changed from 01/10/2017 to 10/10/2019.
