Treatment of clozapine associated obesity and diabetes with exenatide in people with schizophrenia

• Register: ANZCTR
• Last refreshed on: 21 August 2023
• Main ID: ACTRN12615000524594
• Date of registration: 26/05/2015
• Prospective Registration: Yes
• Primary sponsor: The University of Queensland
• Public title: Treatment of clozapine associated obesity and diabetes with exenatide in people with schizophrenia
• Scientific title: A pilot study on the effect of once weekly exenatide compared to treatment as usual for weight loss and glycaemic control in schizophrenia patients with obesity and diabetes
• Date of first enrolment: 24/03/2016
• Target sample size: 60
• Recruitment status: Stopped early
• URL: https://anzctr.org.au/ACTRN12615000524594.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Open (masking not used);Assignment: Parallel;Type of endpoint: Safety/efficacy;
• Phase: Phase 4

Countries of recruitment

Australia

Contacts

• Name: A/Prof Dan Siskind

• Name: A/Prof Dan Siskind

Key inclusion & exclusion criteria

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


Age minimum: 18 Years
Age maximum: 64 Years
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Diet and Nutrition - Obesity

Treatment resistant schizophrenia;obesity;diabetes;
Treatment resistant schizophrenia
obesity
diabetes

Mental Health - Schizophrenia

Metabolic and Endocrine - Diabetes

Intervention(s)

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

Primary Outcome(s)

Weight loss for subjects in Arm 2, as measured by the proportion of people with >5% weight loss.[Body weight will be measured at baseline and at each 4-weekly study visit. Body weight at endpoint (week 24) will be evaluated against baseline weight.]

Weight loss for subjects in Arm 1, as measured by the proportion of people with >5% weight loss.[Body weight will be measured at baseline and at each 4-weekly study visit. Body weight at endpoint (week 24) will be evaluated against baseline weight.]

Acceptability as assessed by a patient-reported outcome questionnaire (designed specifically for this study).[Patient-report outcomes will be assessed after 12 and 24 weeks. ]

Secondary Outcome(s)

Primary Outcome: Tolerability as measured by adverse event reports and study dropout rates.

Known adverse events of exenatide include transient gastrointestinal side effects (nausea, vomiting, diarrhoea), injection site reactions (redness, itchiness, haematoma), dyspepsia and hypoglycaemia (mainly when used with a sulphonylurea or insulin). Rarely, altered renal function and pancreatitis have been reported. [Adverse events and dropouts will be assessed at every 4-weekly study visit. ]

Change in metabolic markers from baseline[Fasting plasma glucose, fasting triglycerides, LDL and HDL will be measured at baseline and at week 12 and 24. In Arm 2, HbA1c will be assessed as a secondary outcome at baseline and 24 weeks. In Arm 1, HbA1c will be assessed as a secondary outcome at baseline, week 12 and 24 weeks. ]

Change in insulin sensitivity as determined by homeostatic model assessment (HOMA)[Fasting plasma insulin will be measured at baseline, week 12 and week 24 to allow calculation of insulin sensitivity. ]

Change in symptoms of psychosis, as measured by the Brief Psychiatric Rating Scale-Anchored (BPRS-A) score[The BPRS-A will be administered at baseline and at week 12 and 24]

Secondary ID(s)

Nil known

Source(s) of Monetary Support

Rebecca L Cooper Medical Research Foundation

Princess Alexandra Hospital Research Support Scheme

Secondary Sponsor(s)

A/Prof Dan Siskind

Ethics review

Status: Approved
Approval date: 19/05/2015
Contact:

Metro South Health Service District Human Research Ethics Committee (EC00167)

Results

• Results available: Yes
• Date Posted: 15/08/2023
• Date Completed: 21/07/2017