Sequential or CombinaTion Anti-obesitY Medication With Muscle Preservation for Weight Loss and MaintEnance: A PragmAtic Randomized CoNtrolled Trial (STAY-LEAN Trial)

Summary

This is a prospective, pragmatic, 21 month, single-center, randomized, 2-phased, open-label, parallel-group trial comparing the use of enhanced lifestyle changes (ELC) in two different sequential anti obesity medication (AOM) therapies. The ELC consists of a medically-supervised and comprehensive weight loss program (Cleveland Clinic's Department of Endocrinology, Diabetes and Metabolism's Integrated Weight Management Program). In the first phase (9 months) of the study, all participants will receive tirzepatide 15 mg (option #1) or semaglutide 2.4 mg if tirzepatide is not tolerated. In the second phase, after completing 9 months of tirzpeatide or semaglutide, participants will continue ELC and will be randomly assigned to a different oral AOM therapy for another 12 months: group 1 (phentermine-topiramate or naltrexone-bupropion) or group 2 (orlistat).

The primary endpoint will be the percentage weight loss at 21 months compared to weight loss at 9 months. The goal will be to show superiority of the arm receiving ELC plus AOM therapy (phentermine-topiramate or naltrexone-bupropion) when compared to the other AOM therapy group (orlistat). Secondary and exploratory endpoints will include percentage of fat mass loss, lean muscle mass, functional capacity, muscle strength and compliance to enhanced lifestyle changes. Informed consent will be obtained. IRB approval of the study will be obtained.

Conditions

• Obesity

Interventions

OTHER

Comprehensive weight loss

Shared Medical Appointments

OTHER

Enhanced lifestyle changes

Subjects will also be referred to an exercise physiologist for a personalized physical activity program. Physical Activity and Exercise will be discussed during SMAs as well and individually as needed for exercise progression The participants exercise prescription will be individualized based on an initial assessment. Exercise duration and progression will be recommended at the discretion of staff and exercise physiologist. The exercise program will be structured but flexible, which means patients can substitute group exercises with individual exercise if necessary, following the FITT-VP format (frequency, intensity, time, type, volume and progression). Patients can reduce exercise frequency if the duration is prolonged, or intensity is increased. Investigators will encourage patients to use Cleveland Clinic gyms across the enterprise.

DRUG

Phentermine-Topiramate

Medication for chronic weight management (Rx)

DRUG

Naltrexone-Bupropion Combination

Medication for chronic weight management (Rx)

DRUG

Orlistat

Medication for chronic weight management (Rx)

Sponsors & Collaborators

• The Cleveland Clinic

  lead OTHER

Principal Investigators

• Bartolome Burguera, M.D · The Cleveland Clinic

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

25 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-03-01

Primary Completion

2027-04-28

Completion

2028-04-28

FDA Drug

Yes

Countries

• United States

Study Locations