High-protein plUs reSistance Training in gLucagon-like pEptide 1 Receptor Agonist Users (HUSTLE)

NCT07700030 | Not Yet Recruiting

• 1 other identifier: 26-00168
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to examine the effects of a high-protein diet (HP) paired with resistance training (RT) compared with a HP diet alone, on skeletal muscle mass (SMM) volume of the (a) quadriceps and (b) rhomboids, and upper and lower body muscle strength in adults recently prescribed tirzepatide. The secondary objectives of this study are to compare changes in resting energy expenditure (REE), adaptive thermogenesis (AT), and body adiposity (SFV, VAT, and intramuscular FF) in the quadriceps and rhomboid muscles) between the high-protein diet with RT and the high-protein diet arms at 6 months.

Conditions

Weight Loss

Keywords

GLP-1; tirzepatide

Outcome Measures

Primary Outcomes (4)

• Changes in lean Skeletal Muscle Mass (SMM) quadriceps

  SMM will be assessed via MRI.

  Baseline, Month 6

• Changes in lean Skeletal Muscle Mass (SMM) rhomboids

  SMM will be assessed via MRI.

  Baseline, Month 6

• Changes in 3-Repetition Maximum (3RM) Bench Press

  Baseline, Month 6

• Changes in 3-Repetition Maximum (3RM) Leg Press

  Baseline, Month 6

Secondary Outcomes (5)

• Changes in Resting Energy Expenditure (REE)

  Baseline, Month 6

• Changes in Adaptive Thermogenesis (AT)

  Baseline, Month 6

• Changes in subcutaneous fat volume (SFV)

  Baseline, Month 6

• Changes in visceral adipose tissue (VAT)

  Baseline, Month 6

• Changes in intramuscular fat fraction (FF)

  Baseline, Month 6

Study Arms (2)

High Protein (HP) Resistance Training (RT)

EXPERIMENTAL

All participants will receive a HP dietary prescription targeting 2.5 g/kg fat-free mass (FFM)/day delivered by an RDN. Participants in the HP-RT arm will additionally complete supervised resistance training 2 days/week for 6 months under the guidance of a personal trainer/Certified Strength and Conditioning Specialist (CSCS).

Other: High protein diet; Behavioral: Resistance Training (RT) Programs

High Protein (HP)

ACTIVE COMPARATOR

All participants will receive a HP dietary prescription targeting 2.5 g/kg FFM/day delivered by an Registered Dietitian Nutritionist (RDN).

Other: High protein diet

Interventions

High protein diet OTHER

The standardized highprotein diet counseling focuses on achieving 2.5 g/kg FFM/day of dietary protein through food and commercially available protein powder supplements that will be provided to participants.

High Protein (HP); High Protein (HP) Resistance Training (RT)

Resistance Training (RT) Programs BEHAVIORAL

Supervised RT program designed for muscle hypertrophy (2 sessions/week, \~45-60 minutes each)

High Protein (HP) Resistance Training (RT)

Eligibility Criteria

• Age: 30 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 30- 60 years
• BMI 27.0-37.0 kg/m² at screening
• English speaking (at this time, MyNetDiary, a food-logging app used for tracking protein-intake, is only set up for English, and our RDN is only capable of providing nutritional counseling in English)
• Received a prescription for tirzepatide, a second-generation oral or injectable dual GIP/GLP-1 receptor agonist (Zepbound/Mounjaro) that is FDA-approved for obesity; and
• Has not yet started tirzepatide and agrees to complete a 4-week run-in period at the initial dose with \<3% weight loss from baseline; OR
• Has initiated tirzepatide and is within the first 4 weeks at the initial dose with \<3% weight loss from pre-treatment baseline.
• On a stable regimen for major chronic conditions (e.g., antihypertensives, lipid-lowering agents, oral antidiabetics, hypothyroidism) for ≥ 8 weeks prior to enrollment.
• Willing and able to:
• (i) Receive high-protein diet counseling and attempt to achieve \~2.5 g/kg FFM /day protein;
• (ii) Attend scheduled nutrition telehealth visits with an RDN;
• (iii) Medically cleared for moderate-intensity resistance training 2 days/week (no condition that would preclude safe participation in either diet-only or diet plus resistance training).
• Willing and able to undergo whole-body MRI at baseline and 6 months without sedation.
• Able to understand procedures and provide written informed consent in English (at this time, MyNetDiary, a food-logging app used for tracking protein-intake, is only set up for English, and our RDN is only capable of providing nutritional counseling in English)

You may not qualify if:

• Patients currently prescribed oral or injectable incretin mimetics containing GLP-1RAs, including Exenatide, Liraglutide, Lixisenatide, Dulaglutide, Semaglutide. Participants who are currently prescribed tirzepatide and have been using for \>4 weeks will also be excluded.
• Prior use of incretin mimetics containing GLP-1RAs with \>3% weight loss in a 4-week period
• Lost \>5% body weight in the past 6 months
• Has consistently resistance trained (\>10 sessions) in the last year
• Currently taking medication or supplements that have been shown to impact muscle function and muscle mass in the last 6 months
• Participants who live outside of the tri-state area and/or are not willing to come to New York City for in-person visits outlined
• Plans to be out of town more than 2 consecutive weeks or \>6 weeks total over the next 6 months
• Type 1 or 2 diabetes; uncontrolled diabetes (e.g., HbA1c \> 6.4% if specified); recurrent severe hypoglycemia or hypoglycemia unawareness.
• Moderate-to-severe chronic kidney disease (e.g., eGFR \< 45-60 mL/min/1.73 m2 final cutoff per protocol) or other renal disease
• Decompensated cirrhosis, severe chronic liver disease, or active liver disease
• Unstable cardiovascular disease (e.g., myocardial infarction (MI), stroke, coronary revascularization, or hospitalization for unstable angina or decompensated heart failure (HF) within \<6 months)
• Active malignancy requiring systemic therapy in the past 6-months (excluding non-melanoma skin cancer)
• Serious medical/psychiatric conditions making participation unsafe or likely to impair adherence
• Pregnant, planning pregnancy within 6 months, or breastfeeding; women of childbearing potential unwilling to use effective contraception per institutional/drug-label guidance.
• Conditions requiring protein restriction (e.g., advanced Chronic Kidney Disease (CKD), relevant inborn errors of metabolism).

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Langone Health

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Weight Loss

Interventions

Diet, High-Protein; Resistance Training

Condition Hierarchy (Ancestors)

Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Physical Therapy Modalities; Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Collin Popp, PhD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Charlie Thao

CONTACT

646-939-1789; Charlie.thao@nyulangone.org

Margaret Curran

CONTACT

609-933-4013; Margaret.Curran@nyulangone.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2026
• First Posted: July 13, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: July 13, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)