Obesity
Conditions
Keywords
Obesity, research
Brief summary
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 1. Form a PPI group to refine the study protocol and establish study materials, 2. 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, 3. 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.
Interventions
BEHAVIORALResistance 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.
DIETARY_SUPPLEMENTProtein 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.
Sponsors
Dasman Diabetes Institute
University of Glasgow
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)
Masking description
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.
Intervention model description
This will be a 6-month 4 arm (control, resistance exercise, protein intake and resistance exercise + protein intake) randomised controlled trial in people with obesity upon initiation of semaglutide/tirzepatide therapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>/= 18 years * BMI \>/= 27 kg/m2
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MRI measured quadriceps cross sectional area (CSA) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MRI measured intramuscular fat content (total thigh) | From enrollment (at baseline) to the end of treatment at 6 months. | investigators will quantify intramuscular fat content |
| MRI measured liver fat | From enrollment (at baseline) to the end of treatment at 6 months. | investigators will also assess liver fat using 3-D sequence (MR-Touch) magnetic resonance elastography (MRE |
| MRI measured liver stiffness | From enrollment (at baseline) to the end of treatment at 6 months. | investigators will also assess liver stiffness using an IDEAL scan. |
| Body Composition via DEXA scan | From enrollment (at baseline) to the end of treatment at 6 months. | fat and fat free mass via Dual Energy X-ray Absorptiometry (DEXA) |
| Muscle strength | From enrollment (at baseline) to the end of treatment at 6 months. | Grip strength will be measured 3 times in each hand using a Jamar dynamometer. |
| Chair rise performance | From enrollment (at baseline) to the end of treatment at 6 months. | The number of chair rises completed in 30 seconds measured. |
| Gait Speed | From enrollment (at baseline) to the end of treatment at 6 months. | Habitual gait speed will be measured during a 4 metre walk test |
| Aerobic Fitness | From enrollment (at baseline) to the end of treatment at 6 months. | Aerobic fitness will be quantified with the 6 min walk test. |
| Whole blood glycated haemoglobin (HbA1c) | 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. | investigators will measure aspartate amino transferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), albumin (ALB), total protein (TP), gamma-glutamyltransferase (GGT) and bilirubin. |
| eGFR | From enrollment (at baseline) to the end of treatment at 6 months. | investigators will assess kidney function by estimating the glomerular filtration rate (eGFR). |
| Blood lipids profile | From enrollment (at baseline) to the end of treatment at 6 months. | investigators will assess participants' lipid profiles by measuring the concentrations of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), triglycerides (TG), and total cholesterol. |
| Fibrosis-4 (FIB-4) Index Score | From enrollment (at baseline) to the end of treatment at 6 months. | Fibrosis-4 (FIB-4) Index score will be calculated using liver function test parameters, including age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count. The FIB-4 index is a continuous score used to estimate the degree of liver fibrosis. There is no fixed minimum or maximum value; however, higher scores indicate more advanced liver fibrosis and therefore a worse outcome. |
| hsCRP | 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. | investigators will assess participants' inflammatory profiles by measuring the circulating levels of interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-1 receptor antagonist (IL-1Ra), and tumor necrosis factor-alpha (TNF-α). |
| Oral glucose tolerance test | From enrollment (at baseline) to the end of treatment at 6 months. | An oral glucose tolerance test will be performed with a cannula inserted and a baseline blood sample collected, a 75g glucose load consumed and further samples collected at 15, 30, 60 90 and 120 min. Samples will be analysed for glucose and insulin levels. |
| Physical Activity Level | From enrollment (at baseline) to the end of treatment at 6 months. | Participants will complete International Physical Activity Questionnaire (IPAQ) which measures physical activity across multiple domains (e.g., work, transport, domestic, and leisure activities). The IPAQ provides a continuous score expressed in Metabolic Equivalent of Task (MET)-minutes per week. The total score has no fixed minimum or maximum value; higher scores indicate higher levels of physical activity, and therefore represent a better outcome (greater physical activity). |
| Sleep Quality and Disturbances | From enrollment (at baseline) to the end of treatment at 6 months. | Sleep quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI), a validated questionnaire that evaluates sleep quality and sleep disturbances over a 1-month period. The PSQI generates a global score ranging from 0 to 21, where higher scores indicate poorer sleep quality (worse outcome). |
| Health-Related Quality of Life | From enrollment (at baseline) to the end of treatment at 6 months. | Health-related quality of life will be assessed using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L). This standardized instrument measures health status across five domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Responses are converted into a single utility index score. The EQ-5D-5L index score typically ranges from less than 0 (states worse than death) to 1 (full health), where higher scores indicate better health-related quality of life (better outcome). |
| Baseline Dietary intake | Assessed at baseline (enrollment). | Baseline dietary intake will be assessed using the EatWellQ8 Food Frequency Questionnaire (FFQ), a validated dietary assessment tool for the Kuwaiti population. The FFQ is used to estimate habitual dietary intake across food groups and nutrients over a defined recall period. The questionnaire generates continuous estimates of dietary intake based on reported frequency of consumption of food items and standard portion sizes (grams). There is no fixed minimum or maximum score. Higher values indicate greater consumption of the corresponding food or nutrient, with interpretation dependent on the specific dietary component being analyzed. |
| Macronutrient Intake | From enrollment (at baseline) to the end of treatment at 6 months. | Baseline carbodhyrate, fat and protein intake (all g/day) will be quantified by the use of the EPIC food frequency questionnaire and multi-pass 24h recall. Further 24h recalls will be carried out at 0.5,1,3 and 6 months of the follow up period. |
| Activities of Daily Living | From enrollment (at baseline) to the end of treatment at 6 months. | Activities of daily living will be assessed using the Barthel Index of Activities of Daily Living, a validated scale that measures functional independence in personal care and mobility tasks (e.g., feeding, bathing, grooming, dressing, bowel and bladder control, toileting, transfers, mobility, and stair climbing). The Barthel Index generates a total score ranging from 0 to 100, where higher scores indicate greater independence in activities of daily living (better outcome), and lower scores indicate greater dependency (worse outcome). |
| Concomitant medication Use | From enrollment (at baseline) to the end of treatment at 6 months. | Concomitant medication use will be assessed by systematic documentation of all medications taken by participants throughout the study period, including prescription medications, over-the-counter drugs, and dietary supplements. Data will be collected at each study visit through structured participant interviews and review of medical records. Medications will be recorded descriptively and categorized by therapeutic class, dose, frequency, and duration of use. |
Countries
Kuwait
Contacts
CONTACTDr Ebaa Al Ozairi
CONTACTProf Stuart Gray
Outcome results
None listed