2026-526200-69-00RecruitingPhase 4
A Phase IV, Randomized Controlled Trial to Evaluate the Effects of Resistance Training Versus Usual Care on Thigh Muscle Volume During Treatment with the Dual GIP/GLP-1 Receptor Agonist Tirzepatide in Adults with Obesity
Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)2 sites in 1 country150 target enrollmentStarted: June 30, 2026Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 4
- Status
- Recruiting
- Sponsor
- Enrollment
- 150
- Locations
- 2
- Primary Endpoint
- Change in contractile thigh muscle volume (mL), as assessed by magnetic resonance imaging (MRI)
Study Overview
Brief Summary
To evaluate the effect of resistance training on changes in contractile skeletal muscle volume during treatment with tirzepatide
Eligibility Criteria
- Ages
- 18 years to 64 years (18-64 Years)
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Are ≥18 years and ≤60 years of age
- •Have a BMI of ≥ 30 kg/m2
- •Have a history of at least 1 self-reported unsuccessful dietary effort to lose body weight
- •In the investigator’s opinion, are well motivated, capable, and willing to learn how to self-inject the IMP, as required for this protocol, inject the IMP, and comply with trial procedures for the duration of the trial, including adherence to scheduled visits, the prescribed resistance training program (if assigned to the experimental group), lifestyle recommendations, and other requirements as specified in the protocol
- •Women of childbearing potential (WOCBP) may be enrolled only if one of the following applies: They are completely abstinent as their preferred and usual lifestyle or exclusively in a same-sex relationship as their preferred and usual lifestyle and agree to remain abstinent or stay in a same-sex relationship without sexual relationships with males until 30 days after the last injection (> 5 half-lives of tirzepatide). They have a negative serum pregnancy test result at screening followed by a negative urine result ≤ 24 hours prior to the first injection, and they agree to use, from screening until 30 days after the last injection, either: one highly effective method of contraception (failure rate <1% per year) or two complementary forms of effective contraception
- •Are sufficiently proficient in German to understand the trial procedures and informed consent information
- •Are capable of providing written informed consent
Exclusion Criteria
- •Have known Type 1 Diabetes, a history of Type 2 Diabetes (including those in remission), a history of ketoacidosis of any aetiology, or a history of hyperosmolar hyperglycaemic state or coma
- •Have uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg)
- •Have any visual, neurological, musculoskeletal, or other physical impairment that, in the opinion of the investigator, would prevent the participant from independently and appropriately self-administering the IMP and/or performing the resistance training program as required by the protocol (e.g., significant muscle or joint pain, significantly limited range of motion)
- •Have renal impairment measured as estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2, calculated by Chronic Kidney Disease Epidemiology (CKD-EPI) 2021 creatinine-based equation during screening
- •Have a known clinically significant gastric emptying abnormality (e.g., severe gastroparesis or gastric outlet obstruction) or chronically take drugs that directly affect gastrointestinal motility
- •Have a history of chronic or acute pancreatitis
- •Have thyroid-stimulating hormone (TSH) outside the range of 0.4 to 6.0 mIU/L at the screening visit
- •Have a history of significant active or unstable major depressive disorder or other severe psychiatric disorder (e.g., schizophrenia, bipolar disorder) or other serious mood or anxiety disorder within the last 2 years
- •Have a PHQ-9 score of 15 or more during screening
- •Have acute suicidality, defined as endorsement of Item 4 and/or Item 5 of the Columbia-Suicide-Severity Scale (C-SSRS) at screening, or any other condition that, in the judgment of the investigator, indicates a significant and immediate risk of suicide
- •Have a history of lifetime suicidal behavior, defined as any positive response within the “Suicidal Behavior” section of the C-SSRS (except non-suicidal self-injurious behavior)
- •Have at least one laboratory value suggestive of diabetes during screening including: glycated hemoglobin A1c (HbA1c) ≥6.5% (≥48 mmol/mol); fasting glucose ≥126 mg/dL (≥7.0 mmol/L)
- •Have acute or chronic hepatitis, signs and symptoms of any other liver disease other than metabolic dysfunction–associated fatty liver disease (MAFLD), or any of the following, as determined during screening: Alanine aminotransferase (ALAT) level >3.0x upper limit of normal (ULN) for the reference range; Total bilirubin level >1.5x ULN for the reference range (except for cases of known Gilbert’s Syndrome)
- •Have a family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome Type 2 or a serum calcitonin level during screening of: ≥20 ng/L, if eGFR ≥60 mL/min/1.73 m2, or ≥35 ng/L, if eGFR <60 mL/min/1.73 m2
- •Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years
- •Have a history of any other condition, such as known drug, alcohol, or substance abuse (including regular use of marijuana or tetrahydrocannabinol-containing products), a diagnosed eating disorder, or other psychiatric disorder, that, in the opinion of the investigator, may interfere with the participant’s ability to comply with and/or complete the protocol
- •Have had a transplanted organ (other than corneal transplants [keratoplasty]) or awaiting an organ transplant
- •Have any clinically significant hematological condition that may interfere with accurate HbA1c measurement or interpretation (e.g., hemolytic anemias or sickle cell disease)
- •Have any other medical condition not listed above that, based on current clinical guidelines or in the opinion of the investigator, constitutes a contraindication to moderate-to-high intensity resistance training (e.g., active proliferative retinopathy, unstable musculoskeletal, neurological, or cardiovascular conditions, or other conditions associated with an increased risk of SAEs during resistance exercise)
- •Have previously used a GLP-1 receptor agonist or a dual incretin receptor agonist at any time
- •Are currently receiving, or have received within 3 months prior to screening, chronic systemic glucocorticoid therapy (>14 days), or have a clinically significant active autoimmune disease (e.g., lupus or rheumatoid arthritis) that, in the opinion of the investigator, requires or is likely to require systemic glucocorticoid treatment during the trial
- •Have current or history of (within 3 months prior to screening) treatment with medications that may cause significant weight gain, including but not limited to, tricyclic antidepressants, atypical antipsychotics, and mood stabilizers
- •Have a self-reported reduction in body weight >5 kg within 3 months prior to screening
- •Have taken, within 3 months prior to screening, medications (other than GLP-1 or dual GIP/GLP-1 receptor agonists) or alternative remedies that promote weight loss
- •Are currently enrolled in any other clinical study involving an IMP or any other type of medical research judged not to be scientifically or medically compatible with this clinical trial
- •Within the last 30 days of screening, have participated in a clinical trial and received treatment, whether active, or placebo. If the trial involved an IMP, 5 half-lives or 30 days, whichever is longer, should have passed
- •Have participated in structured resistance training program (≥ 2x/week for ≥ 4 consecutive weeks) within the last 3 months
- •Have any contraindication to MRI (e.g., non-MRI-compatible implanted devices, metallic foreign bodies, severe claustrophobia, or body size exceeding MRI scanner limitations [maximum bore diameter 70 cm])
- •Have a planned absence of ≥14 consecutive days (or a total of ≥ 30 days) within the next 6 months that would prevent adherence to scheduled study visits and/or the training intervention
- •Have a prior or planned surgical treatment for obesity (excluding liposuction or abdominoplasty if performed >1 year prior to screening)
- •Have or plan to have endoscopic and/or device-based therapy for obesity or have had device removal within the last 6 months prior to screening (e.g., mucosal ablation, gastric artery embolization, intragastric balloon, duodenal-jejunal endoluminal liner)
- •Have obesity induced by other known endocrinologic disorders (e.g., Cushing syndrome) or diagnosed monogenetic or syndromic forms of obesity (e.g., Melanocortin 4 Receptor deficiency or Prader Willi Syndrome)
- •Are currently breastfeeding
- •Have structural cardiovascular disease (e.g., ischemic cardiovascular disease, heart failure, previous cerebrovascular accident [stroke])
- •Have atrial fibrillation
Arms & Interventions
Mounjaro 2.5 mg/dose KwikPen solution for injection in pre-filled pen, Mounjaro 7.5 mg/dose KwikPen solution for injection in pre-filled pen, Mounjaro 10 mg/dose KwikPen solution for injection in pre-filled pen, Mounjaro 5 mg/dose KwikPen solution for injection in pre-filled pen
Test
Intervention: Mounjaro 2.5 mg/dose KwikPen solution for injection in pre-filled pen (Drug)
Mounjaro 2.5 mg/dose KwikPen solution for injection in pre-filled pen, Mounjaro 7.5 mg/dose KwikPen solution for injection in pre-filled pen, Mounjaro 10 mg/dose KwikPen solution for injection in pre-filled pen, Mounjaro 5 mg/dose KwikPen solution for injection in pre-filled pen
Test
Intervention: Mounjaro 7.5 mg/dose KwikPen solution for injection in pre-filled pen (Drug)
Mounjaro 2.5 mg/dose KwikPen solution for injection in pre-filled pen, Mounjaro 7.5 mg/dose KwikPen solution for injection in pre-filled pen, Mounjaro 10 mg/dose KwikPen solution for injection in pre-filled pen, Mounjaro 5 mg/dose KwikPen solution for injection in pre-filled pen
Test
Intervention: Mounjaro 10 mg/dose KwikPen solution for injection in pre-filled pen (Drug)
Mounjaro 2.5 mg/dose KwikPen solution for injection in pre-filled pen, Mounjaro 7.5 mg/dose KwikPen solution for injection in pre-filled pen, Mounjaro 10 mg/dose KwikPen solution for injection in pre-filled pen, Mounjaro 5 mg/dose KwikPen solution for injection in pre-filled pen
Test
Intervention: Mounjaro 5 mg/dose KwikPen solution for injection in pre-filled pen (Drug)
Outcomes
Primary Outcomes
Change in contractile thigh muscle volume (mL), as assessed by magnetic resonance imaging (MRI)
Change in contractile thigh muscle volume (mL), as assessed by magnetic resonance imaging (MRI)
Secondary Outcomes
- Change in body weight (kg), as assessed by a calibrated scale
- Change in anterior thigh intramuscular fat fraction (%), as assessed by MRI
- Change in contractile muscle volume of the combined scapular and upper back musculature (mL), as assessed by MRI
- Change in combined whole-trunk and thigh fat volume (mL), as assessed by MRI
- Change in peak isometric knee extension torque (Nm), as assessed using an isokinetic dynamometer
- Change in maximum handgrip strength (kg), as assessed by a hand dynamometer
- Change in the number of chair stands, as assessed by the 30-second chair stand test
- Change in usual gait speed (m/s), as assessed by the time required to walk 10 meters
- Change in physical health-related QoL, as assessed by the Physical Component Summary score of the Short-Form-36 Health Survey, Version 2, Acute Form (SF-36v2)
- Change in mental health-related QoL, as assessed by the Mental Component Summary score of the SF-36v2
- Change in obesity-specific QoL, as assessed by the Total Score of the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT)
- Change in depressive symptoms, as assessed by the Patient Health Questionnaire-9 (PHQ-9)
- Change in daily moderate-to-vigorous physical activity (MVPA; min/day), as assessed by ActiGraph accelerometry
- Change in skeletal muscle mass (kg), as assessed by bioelectrical impedance analysis (BIA)
- Change in fat mass (kg), as assessed by BIA
- Change in phase angle (°), as assessed by BIA
- Change in absolute maximal oxygen consumption (mL/min), as assessed by cardiopulmonary exercise testing (CPET)
- Change in relative maximal oxygen consumption (mL/kg/min), as assessed by CPET
- Adherence to the IMP, defined as the proportion of prescribed doses administered during the treatment period (%), assessed by injection pen counts
- Highest achieved and maintained (tolerated) dose of tirzepatide during the intervention period, defined as the highest weekly dose level maintained for ≥4 weeks, allowing up to one missed scheduled administration, without subsequent dose reduction and without permanent discontinuation due to intolerance
- Adherence to the resistance training intervention (experimental group only), defined as the mean number of completed training sessions per week during the intervention period, assessed using automatically recorded training data from the exercise devices
Investigators
Präventive Sportmedizin und Sportkardiologie
Scientific
Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)
Study Sites (2)
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