Obstructive Sleep Apnoea and Type 2 Diabetes MedDRA version: 20.0 Level: LLT Classification code 10029983 Term: Obstructive sleep apnoea syndrome System Organ Class: 100000014722 MedDRA version: 20.0 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
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Sponsors
University of Liverpool
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age & reproductive status • Males or females, age 18-75 years. • 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 post-menopausal (see definition below). • 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. Clinical requirements • A clinical diagnosis of type 2 diabetes. • Glycosylated haemoglobin (HbA1c) = 47mmol/mol. * BMI =30 kg/m2 • Currently treated with either diet or any combination of metformin and sulphonylureas (excluding patients treated with DPP-IV inhibitors*, pioglitazone or insulin). • No current use of Liraglutide treatment. • Patients with moderate-severe OSA as assessed by polysomnographic criteria, either by: ? Apnoea-hypopnea index (AHI) =15 events/hour) with overnight domiciliary multichannel sleep study (ResMed, Apnoea Link™ or other suitable alternative). ? Overnight desaturation index (pulse oximetry): ODI =10 (4% dip in oxygen saturation more than 10 events/hour) ? Currently symptomatic for OSA, with excessive daytime sleepiness. *Patients who are currently treated with DPP-IV inhibitors can be included providing the treatment is discontinued before Baseline tests. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 116 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 36
Exclusion criteria
Exclusion criteria: 1. Medical History and Concurrent Diseases • Females of childbearing age who are not using adequate contraceptive methods or who are planning a pregnancy in the next 6 months. • Treatment with DPP-IV inhibitors, pioglitazone or subcutaneous insulin injections or with the anti-obesity medication, orlistat. • Patients in whom there may be occupational implications to a diagnosis of OSA e.g. professional drivers or operating machinery • Type 1 diabetes mellitus. • Congestive heart failure class III-IV. • Renal impairment: eGFR less than 30 ml/minute/1.73m2. • Previous history of acute pancreatitis. • Hyperthyroidism • Hypothyroidism (subjects with a normal TSH and free T4, and on a stable dose of thyroxine for at least 3 months may be included). • Uncontrolled hypertension (blood pressure >170/120 mmHg). • Recent (< 6 months) myocardial infarction. • Previous stroke (with residual neurological deficit). • Significant cardiac dysrhythmias (including pacemaker or ICD). • 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. • Alcohol consumption in excess of daily recommended limits (21 units/week females, 28 units/week males). • Any history of internal metal, pacemakers, or ferromagnetic metallic implants intraocular foreign bodies or cerebral aneurysm clips (exclusion from MR scanning). • History of seizures or unexplained syncope. • Severe sleepiness. Physical and Laboratory Test Findings • Weight <140kg (due to limitations of MRI scanner). Allergies and Adverse Drug Reactions • Subjects with a history of any serious hypersensitivity reaction to GLP1-RA. Sex and Reproductive Status • 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. • Women who are pregnant or breastfeeding. Prohibited Treatments and/or Therapies • Diabetes treated with pioglitazone, GLP-1 analogues or insulin. • Use of other weight loss medication or any drug that might affect body weight or appetite (including anti-depressants, antipsychotics, corticosteroids). • Other Exclusion Criteria • Prisoners or subjects who are involuntarily incarcerated. • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness. Eligibility criteria for this study have been carefully considered to ensure the safety of the study subjects and to ensure that the results of the study can be used. It is imperative that subjects fully meet all eligibility criteria.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective To determine whether twenty six weeks of Liraglutide treatment (up to 1.8mg) can provide a useful treatment for obese patients with T2DM and OSA, either as a stand-alone treatment or as an add-on treatment to continuous positive airway pressure (CPAP). We are primarily concerned with change from baseline in AHI (the principal measure of OSA severity). ;Secondary Objective: Using entirely non-invasive measures to assess changes in fat volume and distribution (visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and liver fat using MRI based techniques), cardiac function using transthoracic echocardiography and flow mediated dilatation. Additionally the trial will provide useful estimates of daytime sleepiness, quality of life, compliance and adverse events. There is an option for participants to provide additional samples for later biochemical analysis. Adipose tissue biopsies from anterior abdominal wall will be taken in a subset of 8 patients per group. If trial participants are interested the researcher will provide more information and there is a separate PIS and ICF for this procedure.;Primary end point(s): Change in apnoea-hypopnea index (AHI) from baseline-post intervention. Although a number of studies using CPAP have instead used the ESS as the primary outcome measure, for the present study, analysis of the ESS may lead to misleading conclusions as excessive daytime sleepiness is very common in obese subjects and is not restricted to those with OSA - particularly in patients with poor glycaemic control (17). ;Timepoint(s) of evaluation of this end point: The trial will run for approximately 3-years. Pre - post measures will be collected from individual participants at 26-week time points prior to and following their respective intervention. See protocol for more detail. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Using entirely non-invasive measures to assess changes in fat volume and distribution (visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and liver fat using MRI based techniques), cardiac function using transthoracic echocardiography and flow mediated dilatation. 1. HbA1c 2. Oxygen desaturation index (ODI) 3. Body Composition: Body weight (kg) Waist: hip ratio Visceral adipose tissue (VAT) Subcutaneous adipose tissue (SAT) Neck tissue volume Neck fat 4. Cardiovascular measures: Flow-mediated dilation (FMD) Carotid intima-media thickness (cIMT) Left ventricular tissue velocity 5. Quality of life: Epworth Sleepiness Scale (ESS) Calgary Sleep Apnoea Quality of Life (SAQLI) SF-36 Oxford Sleep Resistance test (OSLER) Efficacy outcomes include: 1. Compliance: Liraglutide: non-compliance is defined as administration of either less than 80% or more than 120% of their prescribed dose of investigational product. CPAP: non-compliance is defined as less than 2 hours usage. 2. Proportion of adverse events ;Timepoint(s) of evaluation of this end point: The trial will run for approximately 3-years. Pre - post measures will be collected from individual participants at 26-week time points prior to and following their respective intervention. See protocol for more detail. | — |
Countries
United Kingdom
Outcome results
None listed