Functional, Cognitive, and Behavioral Correlates of Resistance Training During Tirzepatide-Induced Weight Loss (RESIST-MIND)

Functional, Cognitive, and Behavioral Correlates of Resistance Training During Tirzepatide-Induced Weight Loss in Adults With Obesity - An Ancillary Study to the RESIST Trial

This study is an ancillary study to the RESIST trial, in which adults with obesity receive the weight-loss medication tirzepatide and are randomly assigned to a structured resistance training program or to usual care for 24 weeks.

RESIST-MIND explores whether resistance training during tirzepatide treatment is associated with changes in attention and concentration, food-related thoughts ("food noise") and food craving, fatigue, sleep quality, everyday functioning, work ability, and motivation for exercise. It also explores whether preserving muscle mass and strength during weight loss is related to these changes. Participants complete questionnaires and a computer-based attention test at the start (Week 0) and at the end (Week 24) of the RESIST treatment period. No additional visits, interventions, or biological samples are part of this ancillary study.

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity (Disorder)
• Intervention / Treatment: Behavioral: Structured resistance training; Drug: Tirzepatide

Detailed Description

RESIST-MIND is a prospective, observational, monocentric ancillary study conducted at the TUM Klinikum, Munich, Germany. Active participation in the RESIST trial (protocol code RESIST-26-HAL-0150-I; EU CT number 2026-526200-69-00) is a prerequisite for enrolment. RESIST is a randomized, controlled, open-label Phase IV trial evaluating a structured resistance training program versus usual care in 150 adults with obesity treated with tirzepatide (Mounjaro®) over 24 weeks. RESIST-MIND involves no investigational medicinal product, no intervention, and no randomization. Assignment to resistance training or usual care occurs exclusively within the RESIST trial.

RESIST-MIND adds validated self-administered questionnaires (MFI-20, PSQI, WHODAS 2.0 12-item, FNQ, FCQ-T-reduced, SSK scale; WAI and WPAI in working participants only) and the electronic d2-R Test of Attention at the RESIST baseline visit (V1, Week 0) and end-of-treatment visit (V7, Week 24). Muscle, strength, body composition, anthropometric and patient-reported data are obtained from the RESIST trial database. All endpoints are exploratory and equally ranked, defined as change from V1 to V7. Between-group differences (resistance training vs. usual care) are estimated using linear models adjusted for baseline. Associations between changes in body composition and changes in the ancillary endpoints are examined across both groups using correlation and multiple linear regression. No formal power calculation or multiplicity adjustment is performed.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Stephan Müller-Stegner, Dr. rer. nat.; Phone Number: +49 89 289 24494; Email: Stephan.Mueller@mri.tum.de
• Study Contact Backup: Name: Katharina Timper, Prof. Dr. med.; Phone Number: +49 89 289 24930; Email: Katharina.Timper@mri.tum.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Participants of the RESIST trial at the TUM Klinikum, Munich:

adults aged 18-60 years with obesity (BMI ≥ 30 kg/m²) without manifest type 2 diabetes or structural cardiovascular disease, eligible for pharmacological weight-loss therapy and suitable for a structured resistance training program. Sufficient command of German is required.

Description

Inclusion Criteria:

• Provisional eligibility for randomization into the RESIST trial (based on all RESIST screening assessments available at the time of informed consent for this ancillary study)
• Written informed consent for this ancillary study

Exclusion Criteria:

• Non-randomization into the RESIST trial for any reason

Key eligibility criteria of the RESIST trial (for context only; full criteria see RESIST protocol RESIST-26-HAL-0150-I):

• Age 18-60 years
• Obesity (BMI ≥ 30 kg/m²)
• No manifest type 2 diabetes
• No structural cardiovascular disease
• Not pregnant or breastfeeding
• Sufficient command of the German language

Study Plan

How is the study designed?

Design Details

• Observational Models: COHORT
• Time Perspectives: PROSPECTIVE

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Resistance training + tirzepatide; RESIST participants randomized to the structured resistance training arm of the RESIST trial, receiving tirzepatide and individualized diet and physical activity counselling. Assignment occurs within RESIST, not within this ancillary study.	Behavioral: Structured resistance training; Machine-based structured resistance training over 24 weeks (approx. 3 sessions per week), delivered within the RESIST trial (not part of this ancillary study). Progressive program with an acclimation phase (weeks 1-4) and a target phase (weeks 5-24; 8-12 repetitions at approx. 70-75% 1-RM, with additional eccentric overload from week 9). Sessions are intended to be fully supervised during the first 6 weeks whenever feasible, thereafter at least one supervised session after each interim visit; remaining sessions at the trial site or at partner fitness facilities.; Drug: Tirzepatide; Once-weekly subcutaneous injection over 24 weeks, starting at 2.5 mg/week and increased by 2.5 mg every 4 weeks as tolerated up to a maximum of 10 mg/week, in accordance with the SmPC. Administered within the RESIST trial (not part of this ancillary study).
Usual care + tirzepatide; RESIST participants randomized to the usual care arm of the RESIST trial, receiving tirzepatide and individualized diet and physical activity counselling. Assignment occurs within RESIST, not within this ancillary study.	Drug: Tirzepatide; Once-weekly subcutaneous injection over 24 weeks, starting at 2.5 mg/week and increased by 2.5 mg every 4 weeks as tolerated up to a maximum of 10 mg/week, in accordance with the SmPC. Administered within the RESIST trial (not part of this ancillary study).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in concentration performance and processing speed	Concentration performance and processing speed computed per the d2-R manual from the electronic administration.	Baseline (Week 0) and end of treatment (Week 24)
Change in food-related cognition	Total score, calculated as the sum of all items.	Baseline (Week 0) and end of treatment (Week 24)
Change in trait food craving	Total score, calculated as the sum of all items; higher scores indicate stronger trait food craving (worse outcome).	Baseline (Week 0) and end of treatment (Week 24)
Change in general functioning	Total score, calculated as the sum of all items; higher scores indicate greater disability (worse outcome).	Baseline (Week 0) and end of treatment (Week 24)
Change in fatigue	Five subscale scores (general fatigue, physical fatigue, reduced motivation, reduced activity, mental fatigue), each the sum of its four items; higher scores indicate more fatigue (worse outcome).	Baseline (Week 0) and end of treatment (Week 24)
Change in subjective sleep quality	Global score (2-week recall), sum of the seven component scores, range 0-21, analysed as a continuous variable; higher scores indicate worse sleep quality. Analysed as a continuous variable.	Baseline (Week 0) and end of treatment (Week 24)
Change in work ability and work productivity - working participants only	WAI items 1, 2, 6 and 7 (raw responses, analysed individually); WPAI scores: % absenteeism, % presenteeism, % work productivity impairment, % activity impairment. Working participants only.	Baseline (Week 0) and end of treatment (Week 24)
Change in self-concordance index of exercise motivation	Self-concordance index of the Self-Concordance of Sport- and Exercise-related Goals scale (SSK), scored according to the original instructions. Higher scores indicate more self-concordant motivation.	Baseline (Week 0) and end of treatment (Week 24)

Collaborators and Investigators

• Sponsor: Technical University of Munich
• Investigators: Principal Investigator: Katharina Timper, Prof. Dr. med., Klinikum der Technischen Universität München (TUM Klinikum); Principal Investigator: StephanStephan Müller-Stegner, Dr. rer. nat., Klinikum der Technischen Universität München (TUM Klinikum)

Study record dates

Study Major Dates

• Study Start (Estimated): October 22, 2026
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: October 17, 2026
• First Submitted That Met QC Criteria: November 5, 2026
• First Posted (Actual): November 10, 2026

Study Record Updates

• Last Update Posted (Actual): November 10, 2026
• Last Update Submitted That Met QC Criteria: November 5, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Keywords: fatigue; body composition; sleep quality; resistance training; attention; food craving; work ability; tirzepatide; exercise motivation; food noise
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Nutrition Disorders; Overnutrition; Body Weight; Sleep Wake Disorders; Overweight; Sleep Disorders, Intrinsic; Dyssomnias; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Fatigue; Sleep Initiation and Maintenance Disorders; Amino Acids, Peptides, and Proteins; Proteins; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Tirzepatide
• Other Study ID Numbers: 2026-342-S-CT; RESIST-26-HAL-0150-I (Other Identifier: TUM Klinikum - protocol code of parent trial RESIST)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Individual participant data will not be shared outside the sponsor institution. Aggregated or fully anonymized data may be made available to researchers upon reasonable request to the Principal Investigators.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No