ClinicalTrials.gg
RecruitingNCT06885736LEAN-PREPUpdated Apr 21, 2026

LEAN Mass Preservation With Resistance Exercise and Protein During Semaglutide/Tirzepatide Therapy

An interventional study of Resistance exercise and Protein Intake in Obesity, sponsored by Dasman Diabetes Institute. Recruiting at 1 site in Kuwait. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-21.

Sponsored by Dasman Diabetes Institute · Not applicable, Interventional, and Basic science

From the registry’s dates

  • Started Aug 2025; still recruiting 1 year 3 months later.
Phase
Not applicable
Study type
Interventional
Enrollment
232
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.
02

Conditions studied

  • Obesity

Browse trials for

Keywords

  • Obesity, research
03

In context

Obesity

11,522 studies on the registry are indexed under Obesity; 2,033 are open to participants now.

This study's planned enrollment of 232 is above the median of 67 across 9,006 interventional studies indexed under Obesity.

Browse Obesity studies →

Lead sponsor

Dasman Diabetes Institute is the lead sponsor of 31 studies on the registry; 14 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Age >/= 18 years
  • >/= 27 kg/m2

Exclusion criteria

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
  • 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 IV CHF
  • Acute or chronic hepatitits, signs and symptoms of any liver disease other than NAFLD, > 3 times the
  • \<45mL/min/1.73m2
  • Significant uncontrolled endocrine abnormaility in the opinion of clinical investigator
  • Evidence of active abnormality that is likely to requite systemic treatment in the next 12 months
  • Had or waiting for an organ transplant
  • History of an active or untreated 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
Terms in these criteria, in plain language(9)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

BMI (body mass index)

Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.

What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

NYHA class (heart failure)

The New York Heart Association’s four classes of how much heart failure limits physical activity.

I
No limits: ordinary activity causes no undue tiredness or breathlessness.
II
Slight limits: comfortable at rest, ordinary activity causes symptoms.
III
Marked limits: comfortable at rest, less than ordinary activity causes symptoms.
IV
Symptoms even at rest; any activity makes them worse.

Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

Autoimmune disease

A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.

Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

05

Study design

Phase
Not applicable
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Outcomes assessor)
Enrollment
232 participants (estimated)

Study arms

  • Experimental
    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.

    Behavioral: Resistance exercise

  • Experimental
    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.

    Dietary Supplement: Protein Intake

  • Experimental
    Resistance exercise + protein intake

    Participants in this arm will follow the above resistance exercise and protein intake interventions.

    Behavioral: Resistance exercise · Dietary Supplement: Protein Intake

  • No intervention
    Control

    Participants assigned to the control group will be asked to maintain their usual exercise habits

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.

    Also known as: leucine

This study also gives Semaglutide, Tirzepatide. No intervention listed here names it: that was found by reading the record.

06

What researchers measure

Primary outcomes

  1. MRI measured quadriceps cross sectional area (CSA)

    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.

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

Secondary outcomes

  1. MRI measured intramuscular fat content (total thigh)

    investigators will quantify intramuscular fat content

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

  2. MRI measured liver fat

    investigators will also assess liver fat using 3-D sequence (MR-Touch) magnetic resonance elastography (MRE

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

  3. MRI measured liver stiffness

    investigators will also assess liver stiffness using an IDEAL scan.

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

  4. Body Composition via DEXA scan

    fat and fat free mass via Dual Energy X-ray Absorptiometry (DEXA)

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

  5. Muscle strength

    Grip strength will be measured 3 times in each hand using a Jamar dynamometer.

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

  6. Chair rise performance

    The number of chair rises completed in 30 seconds measured.

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

  7. Gait Speed

    Habitual gait speed will be measured during a 4 metre walk test

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

  8. Aerobic Fitness

    Aerobic fitness will be quantified with the 6 min walk test.

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

  9. Whole blood glycated haemoglobin (HbA1c)

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

  10. Liver function

    investigators will measure aspartate amino transferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), albumin (ALB), total protein (TP), gamma-glutamyltransferase (GGT) and bilirubin.

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

  11. eGFR

    investigators will assess kidney function by estimating the glomerular filtration rate (eGFR).

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

  12. Blood lipids profile

    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.

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

  13. Fibrosis-4 (FIB-4) Index Score

    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.

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

  14. hsCRP

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

  15. Inflammatory profiles

    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).

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

  16. Oral glucose tolerance test

    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.

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

  17. Physical Activity Level

    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).

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

  18. Sleep Quality and Disturbances

    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).

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

  19. Health-Related Quality of Life

    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).

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

  20. Baseline Dietary intake

    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.

    Time frame: Assessed at baseline (enrollment).

  21. Macronutrient Intake

    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.

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

  22. Activities of Daily Living

    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).

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

  23. Concomitant medication Use

    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.

    Time frame: From enrollment (at baseline) to the end of treatment at 6 months.

07

Study locations

1 of 1 sites recruiting
08

References and documents

Publications

  • Morton RW, Murphy KT, McKellar SR, Schoenfeld BJ, Henselmans M, Helms E, Aragon AA, Devries MC, Banfield L, Krieger JW, Phillips SM. A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults. Br J Sports Med. 2018 Mar;52(6):376-384. doi: 10.1136/bjsports-2017-097608. Epub 2017 Jul 11. PubMed 28698222 ↗
  • Mettler S, Mitchell N, Tipton KD. Increased protein intake reduces lean body mass loss during weight loss in athletes. Med Sci Sports Exerc. 2010 Feb;42(2):326-37. doi: 10.1249/MSS.0b013e3181b2ef8e. PubMed 19927027 ↗
  • Lundgren JR, Janus C, Jensen SBK, Juhl CR, Olsen LM, Christensen RM, Svane MS, Bandholm T, Bojsen-Moller KN, Blond MB, Jensen JB, Stallknecht BM, Holst JJ, Madsbad S, Torekov SS. Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined. N Engl J Med. 2021 May 6;384(18):1719-1730. doi: 10.1056/NEJMoa2028198. PubMed 33951361 ↗
  • Westcott WL. Resistance training is medicine: effects of strength training on health. Curr Sports Med Rep. 2012 Jul-Aug;11(4):209-16. doi: 10.1249/JSR.0b013e31825dabb8. PubMed 22777332 ↗
  • Umpierre D, Ribeiro PA, Kramer CK, Leitao CB, Zucatti AT, Azevedo MJ, Gross JL, Ribeiro JP, Schaan BD. Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes: a systematic review and meta-analysis. JAMA. 2011 May 4;305(17):1790-9. doi: 10.1001/jama.2011.576. PubMed 21540423 ↗
  • Al Ozairi E, Alsaeed D, Al Roudhan D, Jalali M, Mashankar A, Taliping D, Abdulla A, Gill JMR, Sattar N, Welsh P, Gray SR. The effect of home-based resistance exercise training in people with type 2 diabetes: A randomized controlled trial. Diabetes Metab Res Rev. 2023 Oct;39(7):e3677. doi: 10.1002/dmrr.3677. Epub 2023 Jun 17. PubMed 37330638 ↗
  • Alawadhi AA, Alroudhan D, Alsaeed DJ, Almarshad BW, Alshehabi DH, Allahou BA, Mashankar A, Al Ozairi E, Gray S. LEAN mass Preservation with Resistance Exercise and Protein during semaglutide and tirzepatide therapy (LEAN-PREP study): a protocol for a randomised controlled trial. BMJ Open. 2026 Apr 22;16(4):e116911. doi: 10.1136/bmjopen-2026-116911. PubMed 42020128 ↗

Individual participant data

Plan to share: Yes — The individual participant data (IPD) that underlie the results reported in this study, along with the study protocol and statistical analysis plan, will be made available upon reasonable request. Requests should be directed to the corresponding author and will be subject to review to ensure compliance with legal, ethical, and confidentiality requirements.

Supporting information: Study protocol, Statistical analysis plan

Time frame: The data will remain available for 5 years following publication

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 21, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT06885736
Lead sponsor
Dasman Diabetes Institute
Responsible party
Dr. Ebaa Al Ozairi (Chief Medical Officer (CMO), Dasman Diabetes Institute) — Principal investigator
First posted
Mar 20, 2025
Start date
Aug 7, 2025
Primary completion
Aug 30, 2029 (estimated)
Completion
Dec 31, 2029 (estimated)
Last update
Apr 21, 2026

Study contacts

Dr Ebaa Al Ozairi
Contact
ebaa.alozairi@dasmaninstitute.org
+965 22242999 ext. 3111
Prof Stuart Gray
Contact
Stuart.Gray@glasgow.ac.uk
0141 3302569

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drug tested here: Leucine

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