LEAN Mass Preservation With Resistance Exercise and Protein During Semaglutide and Tirzepatide Therapy (LEAN-PREP Study)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 232
- 试验地点
- 1
- 主要终点
- MRI measured quadriceps cross sectional area (CSA)
研究概览
简要总结
The aim of the current study is to determine whether resistance exercise and/or protein intake can preserve lean mass and improve physical function in patients with obesity initiating semaglutide/tirzepatide therapy. To achieve this aim the study will have the following objectives.
In people with obesity initiating semaglutide/tirzepatide therapy
- Form a PPI group to refine the study protocol and establish study materials,
- Quantify the effects of a pragmatic resistance exercise intervention and/or increasing protein intake on lean mass and physical function during semaglutide/tirzepatide induced weight loss,
- Establish whether the resistance exercise intervention and/or increasing protein intake has concomitant benefits on glycaemic control, lipids, liver function, quality of life, physical activity and sleep during semaglutide/tirzepatide induced weight loss.
The participants will:
Begin their weight loss medication, starting at a low dose and then increasing the dose to maximize weight loss. They will be randomly assigned by a computer to ONE of the following groups and will be followed up to 6-months:
- Control group
- Protein intake group
- Muscle strengthening exercise group
- Muscle strengthening exercise AND protein intake group.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Outcomes Assessor)
盲法说明
The researcher and the participant will be blinded to the allocation pattern. It is not possible to blind participants to treatment allocation but people making outcome measurements and performing statistical analysis will be blinded.
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
- •Age >/= 18 years
- •BMI >/= 27 kg/m2
排除标准
- •Currently or in the past 6 months participating in any vigorous aerobic activity (>1h per week) or any resistance exercise.
- •BP of 160/100mmHg or higher
- •Any known medical condition that prevents participants from exercising safely
- •A personal or family history of medullary thyroid carcinoma
- •Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- •History of chronic or acute pancreatitis
- •History of proliferative diabetic retinopathy or diabetic maculopathy
- •History of ketoacidosis or hyperosmolar state/coma
- •History of severe hypoglycaemia and/or hypoglycaemia unawareness within last 6 months
- •Clinically significant gastric emptying abnormality or have undergone or plan to undergo gastric bypass or restrictive bariatric surgery or chronically taking drugs that directly affect GI motility
- •Any of the following CV conditions in last 2 months: acute MI, stroke or hospitilisation due to CHF
- •History of NYHA IV CHF
- •Acute or chronic hepatitits, signs and symptoms of any liver disease other than NAFLD, ALT > 3 times the upper limit of normal
- •eGFR <45mL/min/1.73m2
- •Significant uncontrolled endocrine abnormaility in the opinion of clinical investigator
- •Evidence of active autoimmune abnormality that is likely to requite systemic glucocorticoid treatment in the next 12 months
- •Had or waiting for an organ transplant
- •History of an active or untreated malignancy or in remission from a clinically significant malignancy for less than 5 years
- •Any other aspect of history or condition that may limit the ability of the patient to complete the study
- •Having been treated with prescription drugs that promote weight loss in the last 3 months
- •Receiving chronic systemic glucocorticoid therapy within last month
研究组 & 干预措施
Resistance exercise + protein intake
Participants in this arm will follow the above resistance exercise and protein intake interventions.
干预措施: Protein Intake (Dietary Supplement)
Control
Participants assigned to the control group will be asked to maintain their usual exercise habits
Resistance exercise
Participants assigned to the resistance exercise group will be asked to perform exercises 3 times a week for the intervention period. The first 3 sessions of the exercise will be performed under the supervision of a qualified exercise specialist to ensure that the participants are happy with the exercises and are performing them appropriately. These will also be group sessions to encourage participants to build social connections to support them during the intervention. A similar group social session will take place at week 4 and then every 4 weeks of the study to overcome any issues with the exercises and to ensure progression to an appropriate intensity.
干预措施: Resistance exercise (Behavioral)
Protein Intake
The aim of this arm of the intervention is to ensure a protein intake of 1.6g/kg/day, as this was the intake level identified as the level after which no further effect was found on muscle mass in the meta-regression from (Morton et al., 2018). For the initial 2 weeks of the study, investigators will ask participants to consume 2 protein drinks, containing 25g protein (3g leucine), per day - one in the morning and one in the evening. At this stage, investigators won't know the magnitude of reduction of protein intake following initiation of semaglutide/tirzepatide treatment. After 2 weeks, when the first assessment of dietary intake after beginning semaglutide/tirzepatide treatment occurs, the additional protein will be based on the amount required to ensure 1.6g/kg/day with an aim to spread protein evenly across the day and aim for at least 25g protein (3g leucine) per meal or snack.
干预措施: Protein Intake (Dietary Supplement)
Resistance exercise + protein intake
Participants in this arm will follow the above resistance exercise and protein intake interventions.
干预措施: Resistance exercise (Behavioral)
结局指标
主要结局
MRI measured quadriceps cross sectional area (CSA)
时间窗: From enrollment (at baseline) to the end of treatment at 6 months.
At the mid-point of the thigh, investigators will measure the cross-sectional area of the quadriceps muscle and quantify muscle's thickness and size.
次要结局
- MRI measured liver stiffness(From enrollment (at baseline) to the end of treatment at 6 months.)
- eGFR(From enrollment (at baseline) to the end of treatment at 6 months.)
- Blood lipids profile(From enrollment (at baseline) to the end of treatment at 6 months.)
- Fibrosis-4 (FIB-4) Index Score(From enrollment (at baseline) to the end of treatment at 6 months.)
- Inflammatory profiles(From enrollment (at baseline) to the end of treatment at 6 months.)
- Physical Activity Level(From enrollment (at baseline) to the end of treatment at 6 months.)
- Sleep Quality and Disturbances(From enrollment (at baseline) to the end of treatment at 6 months.)
- Health-Related Quality of Life(From enrollment (at baseline) to the end of treatment at 6 months.)
- Baseline Dietary intake(Assessed at baseline (enrollment).)
- Concomitant medication Use(From enrollment (at baseline) to the end of treatment at 6 months.)
- MRI measured liver fat(From enrollment (at baseline) to the end of treatment at 6 months.)
- MRI measured intramuscular fat content (total thigh)(From enrollment (at baseline) to the end of treatment at 6 months.)
- Muscle strength(From enrollment (at baseline) to the end of treatment at 6 months.)
- Energy intake(From enrollment (at baseline) to the end of treatment at 6 months.)
- Physical activity and sleep levels(From enrollment (at baseline) to the end of treatment at 6 months.)
- Activities of Daily Living(From enrollment (at baseline) to the end of treatment at 6 months.)
- Whole blood glycated haemoglobin (HbA1c)(From enrollment (at baseline) to the end of treatment at 6 months.)
- Oral glucose tolerance test(From enrollment (at baseline) to the end of treatment at 6 months.)
- Blood lipids(From enrollment (at baseline) to the end of treatment at 6 months.)
- Liver function(From enrollment (at baseline) to the end of treatment at 6 months.)
- Plasma GLP-1 and GIP(From enrollment (at baseline) to the end of treatment at 6 months.)
- Concomitant medication(From enrollment (at baseline) to the end of treatment at 6 months.)
- Fib-4 score(From enrollment (at baseline) to the end of treatment at 6 months.)
- Gait Speed(From enrollment (at baseline) to the end of treatment at 6 months.)
- Chair rise performance(From enrollment (at baseline) to the end of treatment at 6 months.)
- Aerobic Fitness(From enrollment (at baseline) to the end of treatment at 6 months.)
- hsCRP(From enrollment (at baseline) to the end of treatment at 6 months.)
- IL-6, IL-10, IL1Ra and TNF-alpha.(From enrollment (at baseline) to the end of treatment at 6 months.)
- Macronutrient Intake(From enrollment (at baseline) to the end of treatment at 6 months.)
- Quality of Life assessed using the EQ-5D-5L questionnaire(From enrollment (at baseline) to the end of treatment at 6 months.)
- Body Composition via DEXA scan(From enrollment (at baseline) to the end of treatment at 6 months.)
研究者
Dr. Ebaa Al Ozairi
Chief Medical Officer (CMO)
Dasman Diabetes Institute