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

NCT06854614 | Active Not Recruiting Phase 4 FDA Drug

• 1 other identifier: 24-695
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief 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

Outcome Measures

Primary Outcomes (1)

• Weight change

  Weight change from month 9 month to month 21 in body weight (%) between both arms

  month 9 to month 21

Secondary Outcomes (1)

• Change in body weight %

  baseline to month 21

Study Arms (2)

Group 1 AOM

EXPERIMENTAL

Comprehensive weight loss Program + Enhanced lifestyle changes + Group 1 AOM sequential therapy (phentermine-topiramate or naltrexone-bupropion)

Other: Comprehensive weight loss; Other: Enhanced lifestyle changes; Drug: Phentermine-Topiramate; Drug: Naltrexone-Bupropion Combination

Group 2 AOM

EXPERIMENTAL

Comprehensive weight loss + Enhanced lifestyle changes + Group 2 AOM Sequential therapy (orlistat)

Other: Comprehensive weight loss; Other: Enhanced lifestyle changes; Drug: Orlistat

Interventions

Comprehensive weight loss OTHER

Shared Medical Appointments

Group 1 AOM; Group 2 AOM

Enhanced lifestyle changes OTHER

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.

Group 1 AOM; Group 2 AOM

Phentermine-Topiramate DRUG

Medication for chronic weight management (Rx)

Also known as: Qsymia

Group 1 AOM

Naltrexone-Bupropion Combination DRUG

Medication for chronic weight management (Rx)

Also known as: Contrave

Group 1 AOM

Orlistat DRUG

Medication for chronic weight management (Rx)

Also known as: Xenical

Group 2 AOM

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Gender: men and women
• Ethnicity: all ethnic groups
• Age: ≥ 25, \< 65 years
• \. Obesity, BMI ≥ 30 and BMI \< 45 6. An Employee, or the significant other of an employee, that is covered by the Cleveland Clinic Employee Health Plan

You may not qualify if:

• Patients with history of diabetes
• Glomerular Filtration Rate \<30 mL/min/1.73 m2 (calculated by the Chronic Kidney Disease Epidemiology Collaboration Equation, CKD-EPI)
• Current glucocorticoid therapy, except for maintenance glucocorticoid therapy of prednisone 5 mg or equivalent
• Currently or within the past 6 months receiving an anti-obesity medication, or any other medication used for the primary intent of weight loss
• Mental incapacity or language barrier
• Pregnancy or plans to become pregnant within the next 2 years
• Personal or family history of medullary thyroid carcinoma
• Personal or family history of Multiple Endocrine Neoplasia syndrome type 2
• previous history of pancreatitis, history of severe liver disease (Cirrhosis), or severe disease of digestive tract
• History of congestive heart failure
• History of bariatric or metabolic surgery/procedure
• Prior participation in the Endocrinology and Metabolism Institutes Integrated Weight Management Program within the past 3 months
• Contraindication for physical activity or significant physical limitation
• Smoking
• Cardiovascular disease including uncontrolled hypertension, history of arrhythmias or coronary artery disease

Sponsors & Collaborators

• The Cleveland Clinic: lead

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Obesity

Interventions

Qsymia; Naltrexone-Bupropion combination; bupropion hydrochloride, naltrexone hydrochoride drug combination; Orlistat

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals

Study Officials

• Bartolome Burguera, M.D

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

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: Institute Chief

Study Record Dates

• First Submitted: February 21, 2025
• First Posted: March 3, 2025
• Study Start: March 1, 2025
• Primary Completion (Estimated): April 28, 2027
• Study Completion (Estimated): April 28, 2028
• Last Updated: December 12, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)