None listed
Conditions
Brief summary
Schizophrenia has a lifetime risk of 7.2 per 1000 persons with 25-50% of people with schizophrenia failing to respond to typical and atypical antipsychotics. For these people clozapine is the gold standard treatment, however, clozapine greatly increases the risk of weight gain and type 2 diabetes (T2DM) which contribute to cardiovascular disease and premature mortality. Current interventions against antipsychotic-associated metabolic dysregulation are limited and insufficient. The mechanism of action for metabolic abnormalities associated with clz is not completely understood; however, recent pre-clinical models have shown that clozapine causes acute deficits in glucose metabolism. This occurred via suppression of glucagon-like-peptide-1 (GLP-1) levels and these defects could be overcome by treatment with a GLP-1 agonist. Exenatide, a GLP-1 agonist, is available in a once weekly injectable formulation which is practical for this population with poor adherence. Therefore, in consideration of the promising preclinical data, the use of exenatide, which is already known to improve glycaemic control and reduce body weight in subjects with and without T2DM, may represent an effective therapeutic intervention for clozapine-associated obesity and T2DM. Therefore, the present study is a 24-week investigator-initiated, parallel group, randomised, open-label pilot study designed to evaluate the acceptability of exenatide weekly and determine the preliminary clinical efficacy and tolerability of exenatide for weight loss and glycaemic control in clozapine-associated obesity and T2DM. This study also has exploratory objectives to examine the feasibility of recruitment, retention, assessment methods and implementation of this intervention for subsequent larger scale, multicenter studies.
Interventions
Participants will be assigned to Arm 1 or Arm 2 depending on their clinical diagnosis and then randomised to the control or intervention group.
Arm 1: clozapine-treated people with Type 2 Diabetes Mellitus (T2DM).
Intervention group: once weekly exenatide subcutaneous injection (2mg) delivered by a mental health or trial nurse for 24 weeks. Exenatide will be administered in addition to current glucose lowering agents. Note: For participants in the intervention group who are already on a sulfony
Participants will be assigned to Arm 1 or Arm 2 depending on their clinical diagnosis and then randomised to the control or intervention group. Arm 1: clozapine-treated people with Type 2 Diabetes Mellitus (T2DM). Intervention group: once weekly exenatide subcutaneous injection (2mg) delivered by a mental health or trial nurse for 24 weeks. Exenatide will be administered in addition to current glucose lowering agents. Note: For participants in the intervention group who are already on a sulfonylurea (SU) and have a HbA1c equal to or below 7.5%, their SU will be ceased to avoid hypoglycaemia. If the participant's HbA1c is between 7.5% and 8.5%, the dosage of the SU will be halved to avoid hypoglycemia. For participants in the intervention group who are on a SU and have a HbA1c of >8.5% the dose of the SU will be maintained. Control group: treatment as usual; no placebo Arm 2: clozapine-treated obese people (BMI greater than or equal to 30kg/m2) without diabetes. Intervention group: once weekly exenatide subcutaneous injection (2mg) delivered by a mental health or trial nurse for 24 weeks. Exenatide will be administered in addition to current glucose lowering agents. Control group: treatment as usual; no placebo
Sponsors
The University of Queensland
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
Provision of informed consent prior to any study specific procedures Clinical diagnosis of Schizophrenia or Schizoaffective Disorder On oral clozapine for at least 18 weeks Stable body weight (defined as less than 5kg change in weight over the past 3 months before inclusion) For Arm A a) Diagnosis of Type II Diabetes Mellitus b) Current and stable therapeutic doses of oral glucose lowering agents for 3 months prior to recruitment c) BMI greater than or equal to 30kg/m2 and less than 45kg/m2 For Arm B a) BMI greater than or equal to 30kg/m2 and less than 45kg/m2
Exclusion criteria
Pregnancy or lactation Severe gastrointestinal disease Severe renal impairment Allergy/hypersensitivity to investigational product Obesity due to other endocrinologic disorder (e.g Cushing Syndrome) Treatment with corticosteroids or other hormone therapy (except oestrogens or thyroxine) for greater than 10 days Current use of any weight-lowering therapy or previous surgical treatment of obesity Uncontrolled hypertension History of thyroid adenoma or carcinoma Untreated or uncontrolled hypo/hyperthyroidism Acute or chronic pancreatitis or high risk of pancreatitis Concurrent use of insulin For Arm 2: Diagnosis of Diabetes Mellitus Type I or Type II
Outcome results
None listed