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

Official title

LEAN Mass Preservation With Resistance Exercise and Protein During Semaglutide and Tirzepatide Therapy (LEAN-PREP Study)

Overview

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

• Behavioral 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 se
• Dietary supplement 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 reduc

Primary outcome measures

• MRI measured quadriceps cross sectional area (CSA) [Time frame: From enrollment (at baseline) to the end of treatment at 6 months.]

Secondary outcome measures (12)

• MRI measured intramuscular fat content (total thigh) [Time frame: From enrollment (at baseline) to the end of treatment at 6 months.]
• MRI measured liver fat [Time frame: From enrollment (at baseline) to the end of treatment at 6 months.]
• MRI measured liver stiffness [Time frame: From enrollment (at baseline) to the end of treatment at 6 months.]
• Body Composition via DEXA scan [Time frame: From enrollment (at baseline) to the end of treatment at 6 months.]
• Muscle strength [Time frame: From enrollment (at baseline) to the end of treatment at 6 months.]
• Chair rise performance [Time frame: From enrollment (at baseline) to the end of treatment at 6 months.]
• Gait Speed [Time frame: From enrollment (at baseline) to the end of treatment at 6 months.]
• Aerobic Fitness [Time frame: From enrollment (at baseline) to the end of treatment at 6 months.]
• Whole blood glycated haemoglobin (HbA1c) [Time frame: From enrollment (at baseline) to the end of treatment at 6 months.]
• Liver function [Time frame: From enrollment (at baseline) to the end of treatment at 6 months.]
• eGFR [Time frame: From enrollment (at baseline) to the end of treatment at 6 months.]
• Blood lipids profile [Time frame: From enrollment (at baseline) to the end of treatment at 6 months.]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Basic science

Study locations

Kuwait · 1 center

• Dasman Diabetes Institute — Kuwait City

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 J PMID 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. PMID 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. PMID 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. PMID 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. PMID 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. PMID 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. PMID 42020128

Identifiers

NCT: NCT06885736 · RA HM-2025-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗