Effects of Incretin Memetics and Exercise on Gut-brain and Metabolic Health in Persons With Type 2 Diabetes
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Change in insulin resistance (HOMA-IR)
研究概览
简要总结
This study will examine changes in brain and physical health in adults with type 2 diabetes who are initiating incretin-mimetic therapy (e.g., Ozempic, Mounjaro), and determine whether adding structured exercise provides additional benefits. Participants will be randomized to receive incretin-mimetic therapy alone or incretin-mimetic therapy plus a structured exercise program for 24 weeks. If the participant is randomly assigned to the incretin-based therapy alone group, they will have the opportunity to complete the same structured exercise program after the 24-week study period is complete.
Brain health will be assessed through cognitive performance, mental health, and brain-mediated appetite regulation. The study will also assess gut microbiota and motor-cortex neuroplasticity as potential factors associated with changes in brain health, as well as glucose regulation, body composition, physical function, and cardiorespiratory fitness. Assessments will be completed at baseline, 8 weeks, and 24 weeks. Findings will help determine how incretin-mimetic therapy and exercise can be integrated to support brain and physical health in adults with type 2 diabetes.
详细描述
Type 2 diabetes (T2D) is associated with alterations in cognitive function, mental health, and the regulation of appetite and food intake. Incretin-mimetic therapies are increasingly used in the management of T2D and improve glycemic control while reducing appetite and body mass. However, their effects on brain health remain poorly understood. In addition, body mass loss during incretin-mimetic therapy can include loss of lean tissue, which may have implications for metabolic health and physical function. Exercise is a cornerstone of T2D management and has beneficial effects on glycemic control, body composition, physical function, cognitive function, and mental health. Whether structured exercise provides additional brain-health benefits during incretin-mimetic therapy while helping to preserve lean tissue and physical function remains unclear.
The primary objective of this randomized controlled trial is to characterize changes in brain health during incretin-mimetic therapy and determine whether the addition of structured exercise provides additional benefit. Brain health will be considered across three complementary domains: cognitive performance, mental health, and brain-mediated appetite regulation. The study will also examine changes in body composition and metabolic and physical health to determine whether exercise helps preserve lean tissue and physical function during incretin-mimetic therapy.
A secondary objective is to investigate the microbiota-gut-brain axis (MGBA) and motor-cortex neuroplasticity as potential mechanistic correlates of brain-health responses. The MGBA represents bidirectional communication between the gut and brain and may influence cognitive and mental health as well as homeostatic and hedonic regulation of food intake. Gut microbial communities will be characterized using 16S rRNA gene sequencing and bioinformatics to examine changes in microbial diversity and composition.
Motor-cortex neuroplasticity will be assessed using transcranial magnetic stimulation (TMS). A standardized stimulation protocol will be used to induce changes in motor-cortex excitability, with changes in motor-evoked responses used to quantify the neuroplastic response. These measures will be used to investigate whether changes in motor-cortex neuroplasticity are associated with changes in brain-health outcomes.
Together, the study will examine the complementary effects of pharmacological and exercise-based approaches to T2D management and investigate biological factors that may contribute to brain-health responses during treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •adults aged 18 years or older
- •diagnosed with pre diabetes or type 2 diabetes
- •prescribed incretin-based therapy (e.g., semaglutide or tirzepatide)
- •able and willing to participate in the study assessments and, if randomized to the exercise group, the 24-week structured exercise program
- •able to provide informed consent
排除标准
- •current use of incretin-based therapy outside the study-defined enrollment window
- •pregnant or planning to become pregnant during the study period
- •any other medical condition or circumstance that, in the opinion of the research team, would interfere with safe participation or completion of study procedures
研究组 & 干预措施
Incretin Therapy Alone
Participants will receive incretin-based therapy prescribed by their healthcare provider as part of their usual clinical care. No structured exercise intervention will be provided by the research team during the 24-week study period. Participants will complete study assessments at baseline, 8 weeks, and 24 weeks. Following completion of the 24-week study period, participants will have the opportunity to complete the structured exercise program.
Incretin Therapy plus Exercise
Participants will receive incretin-based therapy prescribed by their healthcare provider as part of their usual clinical care and will complete a 24-week structured exercise program. The exercise program will include resistance and aerobic exercise performed three times per week, with exercise type and intensity individualized to participants' abilities and fitness levels. Two sessions per week will be completed at the University of Regina under supervision, and one session per week will be completed independently. Participants will also receive guidance on adequate protein intake. Study assessments will be completed at baseline, 8 weeks, and 24 weeks.
干预措施: Structured Exercise Program (Behavioral)
结局指标
主要结局
Change in insulin resistance (HOMA-IR)
时间窗: Baseline, 8 weeks, and 24 weeks
Insulin resistance will be estimated using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), calculated from fasting glucose and fasting insulin concentrations. Higher HOMA-IR values indicate greater insulin resistance. The primary outcome will be the between-group difference in change in HOMA-IR from baseline to 24 weeks.
次要结局
- Change in Eating Patterns and Behaviours(Baseline, 8 weeks, and 24 weeks)
- Change in cardiovascular health(Baseline, 8 weeks, and 24 weeks)
- Change in body composition(Baseline, 8 weeks, and 24 weeks)
- Change in physical function(Baseline, 8 weeks, and 24 weeks)
- Change in aerobic fitness(Baseline, 8 weeks, and 24 weeks)
研究者
Julia Totosy de Zepetnek
Associate Professor
University of Regina