None listed
Conditions
Brief summary
Obesity and physical inactivity are gateway conditions to prevalent and costly cardiovascular (CV) diseases including hypertension, type 2 diabetes, coronary artery disease, stroke and chronic kidney disease. Previous randomised trials have shown promising impacts on weight loss with the use of a self-administered drug called tirzepatide by modifying hormones released from the gastrointestinal tract, as a strategy for the management of obesity. However, an important issue in this and similar studies relates to the type of weight that was lost. In addition to losing fat, participants treated with tirzepatide can lose lean mass, including skeletal muscle. Maintenance of skeletal muscle mass and function are crucial to avoiding frailty, which is linked to cardiovascular diseases and mortality. Resistance exercise training (involving weight lifting type exercises) is known to increase skeletal muscle mass and function in humans, We hypothesise that: -The combination of tirzepatide and a resistance exercise intervention (targeted at reducing fat and increasing skeletal muscle mass), will optimise changes in body composition in our enrolled population, who are at high risk of future cardiovascular diseases. -Combining tirzepatide with exercise training will optimise vascular function and health in older men and women at high risk of future cardiovascular diseases. -Combining tirzepatide with exercise training will optimise heart function in older men and women at high risk of future cardiovascular diseases
Interventions
Tirzepatide (background therapy, given to all participants):
Doses will be administered as once weekly subcutaneous injections by a research nurse or other qualified research personnel at the study centre. Tirzepatide will be initiated at a dose of 2.5 mg once weekly and increased by 2.5 mg every 4 weeks during the dose-escalation period aiming to reach a maintenance dose of 15 mg once weekly by week 20. Therapy at this dose will continue at either the maximum tolerated dose or at 15 mg for a fu
Tirzepatide (background therapy, given to all participants): Doses will be administered as once weekly subcutaneous injections by a research nurse or other qualified research personnel at the study centre. Tirzepatide will be initiated at a dose of 2.5 mg once weekly and increased by 2.5 mg every 4 weeks during the dose-escalation period aiming to reach a maintenance dose of 15 mg once weekly by week 20. Therapy at this dose will continue at either the maximum tolerated dose or at 15 mg for a further 20 weeks (40 weeks' intervention in total). This intervention period allows for attainment of metabolic benefit and provision of centre-based and supervised exercise interventions, described below. Exercise intervention: Participants randomised to the exercise groups will attend 3 x one-hour exercise sessions per week for 40 weeks. Participants will exercise in group sessions and the program will focus on increasing skeletal muscle mass and function. Exercise sessions will be undertaken in a dedicated research gym at the University of Western Australia, supervised by an Accredited Exercise Physiologist (AEP). The exercise training program will be in line with recommendations for the prescription and programming of resistance training, endorsed by Exercise and Sport Science Australia (ESSA). Exercise will commence with light-moderate intensity exercises and focus on developing correct technique, whilst the participants become accustomed to resistance training. Over the course of the 40-week training program, the intensity will gradually increase to moderate-vigorous exercise. Each 1 hr session will consist of a general whole body warm up, followed by resistance-based exercises involving major muscle groups using a variety of apparatus, including bodyweight exercises, bands, cables, machines, and free-weights. Example exercises are squats, deadlifts, leg-press, lateral pulldowns, shoulder press and chest press. Each session will conclude with a 5 min cool down. Borg's Category Scale will be used to rate perceived exertion during session. A record of attendance will be kept.
Sponsors
The University of Western Australia
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Investigator)
Eligibility
Sex/Gender
All
Age
50 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Men and women aged 50-70 years with body mass index (BMI) greater than or equal to 30 kg/m², or greater than or equal to 27 kg/m² with at least one weight-related comorbidity (e.g. hypertension, dyslipidaemia or obstructive sleep apnoea)
Exclusion criteria
Known pregnancy, cardiovascular disease, diabetes, any history of pancreatitis; any history of multiple endocrine neoplasia (MEN) type 2 or medullary thyroid carcinoma; previous or planned bariatric surgery; any prior use of incretin-based therapies; use of non-incretin based anti-obesity or CV medications (e.g. statins, BP drugs) within 3 months of enrolment; and any other clinically significant illnesses (e.g. cancer, severe respiratory disease). Total cholesterol greater than 7.0 mmol/L, LDL greater than 4.0 mmol/L, eGFR less than 45 mL/min, HbA1c greater than 7.0% and/or evidence of significant liver disease. BP greater than 160/100 mmHg during the clinic visit.
Outcome results
None listed