Effects of Long-Acting GLP-1 (Glucagon-like Peptide-1) or Dual Incretin (GLP-1 and GIP [Glucose-dependent Insulinotropic Peptide]) Modulation on Gastric Motor Functions

NCT06801015 | Active Not Recruiting Phase 4 FDA Drug

• 1 other identifier: 24-011786
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare effects of weekly SQ semaglutide 2.4mg SQ, SQ tirzepatide 10mg, and placebo administered for 24 weeks on GES measured repeatedly at baseline, 16 weeks, 24 weeks, 28 weeks, 4 weeks after stopping the medication, and accommodation and satiation at 24 weeks compared to baseline.

Conditions

Obesity

Outcome Measures

Primary Outcomes (2)

• Gastric emptying of solids T1/2 min, that is time for half meal to empty from stomach

  Gastric emptying of an egg meal measured by scintigraphy

  Measurement at baseline, after 16 and 24 weeks' treatment, and at 28 weeks (off treatment for 4 weeks)

• Body weight

  Measurement of body weight using weight scales

  Measurement at baseline, after 16 and 24 weeks' treatment, and at 28 weeks (off treatment for 4 weeks)

Secondary Outcomes (7)

• Calories to fullness, kilocalories (kcal)

  Measurement at baseline, and after 24 weeks' treatment

• Maximum tolerated calories, kilocalories (kcal)

  Measurement at baseline, and after 24 weeks' treatment

• Fasting gastric volume, milliliters (mL)

  Measurement at baseline, and after 24 weeks' treatment

• Gastric accommodation vol (postprandial minus fasting volume), milliliters (mL)

  Measurement at baseline, and after 24 weeks' treatment

• Peak postprandial GLP-1 (glucagon-like peptide-1) pmol/L

  Measurement at baseline, and after 24 weeks' treatment

Study Arms (3)

semaglutide

EXPERIMENTAL

Administered by subcutaneous injection once per week in accordance with FDA approved escalation as well as maintenance treatment

Drug: Semaglutide

Tirzepatide

EXPERIMENTAL

Administered by subcutaneous injection once per week in accordance with FDA approved escalation as well as maintenance treatment

Drug: Tirzepatide

placebo

PLACEBO COMPARATOR

Administered by subcutaneous injection once per week

Drug: Placebo

Interventions

Tirzepatide DRUG

Both interventions are approved by FDA for the treatment of obesity and are administered by subcutaneous injection once per week

Tirzepatide

Placebo DRUG

Placebo administered by subcutaneous injection once per week.

placebo

Semaglutide DRUG

Both interventions are approved by FDA for the treatment of obesity and are administered by subcutaneous injection once per week

semaglutide

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (18-75 years) who have BMI \>30 or \>27kg/m2 who also have prediabetes or T2DM on diet treatment only
• Able to reside within 50 miles of Mayo Clinic for the duration of the study
• Not currently on treatment (exceptions below) for cardiac, pulmonary, GI, hepatic, renal, hematological, neurological, or endocrine disorders.
• Biological sex: men or women. We shall attempt to recruit equal proportions of men and women. Women of childbearing potential will be using an effective form of contraception and have negative pregnancy tests within 48 hours of enrollment and before each isotope-based radiation exposure as part of the tests for gastric emptying. In addition, monthly urine pregnancy tests will be performed in females with childbearing potential.

You may not qualify if:

• Weight exceeding 137kg (safety limit of camera for measuring gastric volumes)
• Abdominal surgery other than appendectomy, Caesarian section or tubal ligation, cholecystectomy
• Chronic GI diseases, systemic disease or medications that could affect GI motility, appetite or absorption
• Patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia II
• Patients with T2DM on GLP-1RAs, amylin agonists/analogs (e.g. pramlintide), insulin, sulfonylureas (all due to risk of hypoglycemia with semaglutide or tirzepatide treatment); or on metformin, acarbose or DPP-4 inhibitors (e.g. sitagliptin and vildagliptin).
• Past or current history of pancreatitis, gallstones, history of alcoholism, blood triglyceride levels \> 500mg/dL
• Significant untreated psychiatric dysfunction or an active eating disorder (Clark et al 2007, Cunningham et al 2012) based on screening with the Hospital Anxiety and Depression Inventory \[HAD (Zigmond \& Snaith 1983)\], a self-administered alcoholism screening test \[AUDIT-C (Bush et al 1998)\], and the Questionnaire on Eating and Weight Patterns-Revised \[binge eating disorders and bulimia (Yanovski et al 2015)\]. If such a dysfunction is identified by a HAD score \>11 on either the anxiety or depression subscales or difficulties with substance or eating disorders, the participant will be interviewed by a study investigator and, if excluded, will be given a referral letter to his/her primary care doctor for further appraisal and follow-up treatment.
• Intake of any medication (except multivitamins) within 7 days of the study. Exceptions are birth control pill, estrogen and thyroxine replacement, and medication administered for co-morbidities as long as they do not alter gastric functions. Thus, statins for hyperlipidemia, diuretics, β-adrenergic blockers, ACE inhibitors and angiotensin antagonists for hypertension are permissible. In contrast, resin sequestrants for hyperlipidemia (Psichas et al 2012), α2-adrenergic agonists for hypertension, are not permissible due to effects on stomach or appetite.
• Documented delayed gastric emptying: gastric emptying T1/2 \>174 min or gastric retention at 4 hours \>25% based on 5-95%ile of 319 controls' GES of the same meal (320kcal, 30% fat) (Camilleri et al 2012a, Table 1)
• Hypersensitivity to semaglutide or tirzepatide
• Participate in highly intense physical activity program that could potentially interfere with study interpretation

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Obesity

Interventions

semaglutide; Tirzepatide

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

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

Study Officials

• Michael Camilleri

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Concealed allocation with masking of medications administered by subcutaneous injection once per week; blinding of all investigators since medication is dispensed by research pharmacy not by clinical research trials unit
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomized controlled trial of the effects of semaglutide, tirzepatide, and placebo with concealed allocation

Study Record Dates

• First Submitted: January 24, 2025
• First Posted: January 30, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): March 31, 2028
• Last Updated: December 26, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)