GLP-1R Actions on Muscle and the Skeleton

NCT07154719 | Recruiting Phase 4 FDA Drug

• 1 other identifier: PBRC 2024-031
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The GRAMS study objectives are to assess the musculoskeletal changes that occur after weight loss using GLP-1 based therapy. A lifestyle intervention with diet and exercise is included to assess any mitigating effects are provided, versus a control group with regular exercise and diet.

Conditions

Musculoskeletal Abnormalities; Obesity; Sarcopenic Obesity; Osteoporosis; Drug Effect

Keywords

GLP-1 agonists; Obesity treatments; Muscleskeletal loss; Tirzepatide

Outcome Measures

Primary Outcomes (1)

• Changes in fat free mass (FFM) using DXA imaging. FFM equals all body composition that is not fat mass. This includes bone, skeletal muscle, organs, water and all connective tissues. The unit of measurement is in kilograms (kg) at baseline, 3 and 6 mo.

  DXA (Dual energy Xray absorptiometry)

  Baseline and time 3, and 6 months.

Secondary Outcomes (6)

• MRI (thigh) without contrast

  Month 1 (baseline), month 3, month 6 (final visit)

• Osteocalcin

  Month 1 (baseline), month 3, month 6 (final visit)

• Irisin

  Month 1 (baseline), month 3, month 6 (final visit)

• Procollagen 1 N-terminal peptide (P1NP)

  Month 1 (baseline), month 3, and month 6 (final visit)

• C-Terminal Telopeptide of type I collagen (CTX-1)

  Month 1 (baseline), month 3, month 6 (final visit)

Study Arms (2)

Treatment/intervention group

EXPERIMENTAL

Treatment with Tirzepatide for 5 months and lifestyle toolkit.

Drug: Tirzepatide

Control/Placebo

PLACEBO COMPARATOR

Treatment with Tirzepatide for 5 months with regular diet and exercise.

Behavioral: Lifestyle toolkit

Interventions

Tirzepatide DRUG

GLP-1 based treatment for obesity

Treatment/intervention group

Lifestyle toolkit BEHAVIORAL

2 ABBOTT protein shakes daily and resistance-based exercise x 3 days per week.

Control/Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects will have a BMI between 30kg/m2
• kg/m2 (inclusive)
• Be between 18 and 50 years of age (inclusive).
• Non-Hispanic Black males and females will be enrolled at PBRC.
• Rural males and females will be enrolled at MaineHealth.
• Female subjects will be premenopausal.
• Females have had their last menstrual period less than 60 days before screening.
• Females have the absence of menopausal-associated vasomotor symptoms.
• All subjects must be able to use Lifestyle Toolkit as prescribed for intervention arm.

You may not qualify if:

• \- Males and females over the age of 50 years of age
• Menopausal females.
• Subjects on systemic corticosteroids or other agents known to increase loss of muscle and bone mass.
• Subjects who are on medications that increase or decrease weight status.
• Subjects having contraindications to tirzepatide in the package insert.
• Subjects with a history of malignancy other than non-melanoma skin cancer
• Subjects with known osteoporosis or are on osteoporosis therapies (gonadal hormones or hormone antagonists).
• Subjects with uncontrolled thyroid or parathyroid disease that may influence the study results.
• Subjects with a clinically significant hematologic abnormality, kidney disease, liver disease, or diabetes.
• Females of childbearing potential who do not agree to using an effective method of contraception during the study. Medically acceptable methods include oral contraceptive medication, an intrauterine device (IUD), an implantable contraceptive (such as Implanon), or a barrier method (such as condom or diaphragm with spermicide).
• Abstinence is acceptable, as is sexual activity exclusively with same sex partners.
• Fertility Appreciation Based Methods (natural family planning) are also acceptable forms of addressing childbearing potential in all subjects. A urine pregnancy test (UPT) will be performed on all females of childbearing potential at the screening visit, 3 and 6 months.
• Unable to follow Lifestyle Toolkit as prescribed for intervention arm.
• Patient Health Questionnaire-9 (PHQ-9) Score equal to or greater than 15 (clinical depression).
• Adults who are unable to consent.

Sponsors & Collaborators

• Pennington Biomedical Research Center: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Pennington Biomedical Research Center

Baton Rouge, Louisiana, 70808, United States

RECRUITING

Related Publications (4)

• Goodpaster BH, Theriault R, Watkins SC, Kelley DE. Intramuscular lipid content is increased in obesity and decreased by weight loss. Metabolism. 2000 Apr;49(4):467-72. doi: 10.1016/s0026-0495(00)80010-4.

  PMID: 10778870 BACKGROUND

• 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 BACKGROUND

• Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216. doi: 10.1056/NEJMoa2206038. Epub 2022 Jun 4.

  PMID: 35658024 BACKGROUND

• Dubin RL, Heymsfield SB, Ravussin E, Greenway FL. Glucagon-like peptide-1 receptor agonist-based agents and weight loss composition: Filling the gaps. Diabetes Obes Metab. 2024 Dec;26(12):5503-5518. doi: 10.1111/dom.15913. Epub 2024 Sep 30.

  PMID: 39344838 BACKGROUND

MeSH Terms

Conditions

Musculoskeletal Abnormalities; Obesity; Osteoporosis

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Musculoskeletal Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Bone Diseases, Metabolic; Bone Diseases; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Central Study Contacts

Robert L Dubin, MD

CONTACT

9417862130; Robert.Dubin@pbrc.edu

Seaneen Hebert, MS

CONTACT

2257632500; Seaneen.Hebert@pbrc.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Model Details: The investigators will enroll 25 subjects in each study arm. Both arms will involve treatment with a GLP-1 agonist (tirzepatide) for 5 months. The intervention arm will use a lifestyle toolkit which includes protein supplements and resistance-based exercises. The control group will use regular diet and exercise activities. Testing includes DXA and MRI body composition as well as lab tests to assess for muscle skeletal quality and physical fitness.

Study Record Dates

• First Submitted: August 22, 2025
• First Posted: September 4, 2025
• Study Start: October 9, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 16, 2026

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data available 2-3 months after study completion date.
• Access Criteria: Requests for data sharing can be made to study PI (Dubin). The investigators will provide available data using the available resources at the study center.

Locations

US (1)