Evaluation of the Safety and Efficacy of Revita® DMR on Body Weight Maintenance in Subjects With Obesity Who Have Achieved at Least 15% Weight Loss on Tirzepatide

NCT06484114 | Active Not Recruiting DMC FDA Device

• 1 other identifier: C-00700
• Study Type: interventional
• Target: 315
• Locations: 1 country
• Sites: 32

Brief Summary

Fractyl is evaluating Revita Duodenal Mucosal Resurfacing (DMR) in the REMAIN-1 pivotal study, which is designed to include two cohorts - an open label cohort referred to as REVEAL-1, and a randomized cohort, which includes both a midpoint analysis and a pivotal analysis. Patients who previously lost at least 15% of their body weight on a GLP-1 can qualify for the open label REVEAL-1 cohort. The data generated from the REVEAL-1 cohort will be used for open label reporting as the study progresses. The REMAIN-1 randomized cohort will enroll patients living with obesity and a body mass index ("BMI") between 30 and 45 kg/m2 who are not currently on a GLP-1 drug. Patients will be prescribed tirzepatide and titrated to achieve at least 15% total body weight loss, at which time tirzepatide will be discontinued and patients will be randomized to Revita versus sham at 2:1. Midpoint Analysis of Randomized Cohort: The midpoint analysis of the randomized cohort will be performed at three months of follow-up on approximately 45 patients, allowing us to assess and report on safety and efficacy signals that could be anticipated in the pivotal analysis. These patients are distinct from those included in the pivotal analysis. Pivotal Analysis of Randomized Cohort: The pivotal analysis of the randomized cohort will be performed on approximately 315 patients (distinct from those included in the midpoint analysis) and will evaluate safety and efficacy in the first co-primary endpoint, which is weight regain from the time of tirzepatide discontinuation in Revita DMR versus sham patients at six months, with a primary objective of demonstrating a benefit of Revita DMR versus sham for weight maintenance after GLP-1 discontinuation. The second co-primary endpoint evaluates a responder rate among the Revita DMR treated group at one year to demonstrate the durability of the Revita DMR procedure for weight maintenance after discontinuation of a GLP-1-based therapy. Secondary objectives will include evaluation of the effectiveness of the Revita DMR procedure on the change in blood glucose levels, cardiovascular disease ("CVD") risk factors, body composition and pre-diabetes status. All patients enrolled in the study will receive diet and lifestyle counseling.

Conditions

Obesity; Weight Change Trajectory; Weight Change, Body

Keywords

Weight Management; Obesity; Overweight; Weight; Duodenum; Revita; GLP-1; Tirzepatide; Endoscopic; Weight Maintenance

Outcome Measures

Primary Outcomes (2)

• To demonstrate that Revita DMR is superior to sham in percent change in body weight from baseline to week 26

  Percent change in total body weight from baseline to week 26, DMR vs sham

  26 Weeks

• To demonstrate that a majority of Revita DMR participants maintain clinically significant weight loss 52 weeks (1 year) after discontinuing tirzepatide therapy

  Percentage of DMR participants who maintain at least 5% total body weight loss from pre-tirzepatide (week -21) to week 52

  52 weeks

Secondary Outcomes (5)

• To demonstrate durability of DMR

  26 & 52 weeks

• To demonstrate DMR in comparison to sham in change from baseline for total body weight change

  52 Weeks

• To demonstrate DMR in comparison to sham in change from baseline for fating C-peptide

  26 & 52 Weeks

• To demonstrate DMR in comparison to sham in change from baseline for metabolic health

  26 & 52 Weeks

• To evaluate dimensions of upper gastrointestinal distress throughout the study (tirzepatide open-label run in vs. after randomization)

  26 & 52 Weeks

Study Arms (3)

Training

OTHER

Sites will gain experience with the study protocol and the Revita DMR procedure in an open-label, single-arm treatment assignment for participants who previously achieved 15% weight loss using a GLP-1

Device: Revita Duodenal Mucosal Resurfacing (DMR)

Active

ACTIVE COMPARATOR

Patients who have achieved \>15% weight loss from baseline will receive the Revita DMR Procedure

Device: Revita Duodenal Mucosal Resurfacing (DMR)

Sham

SHAM COMPARATOR

Patients who have achieved \>15% weight loss from baseline will receive and endoscopic evaluation and will have a catheter introduced but the Revita DMR procedure will not be performed

Device: Sham

Interventions

Revita Duodenal Mucosal Resurfacing (DMR) DEVICE

DMR is designed to ablate and re-epithelialize the duodenal mucosal surface, thus allowing nutrients to be exposed to a newly regrown and potentially normalized local mucosa. This implies that the duodenal mucosa surface is abnormal in participants associated with metabolic disorders. The Revita DMR procedure is performed endoscopically with supporting fluoroscopy.

Active; Training

Sham DEVICE

An endoscopic review with non active catheter introduction

Sham

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant-provided, written informed consent to participate in the study in accordance with local regulations
• Adult participants aged 21-70 years, inclusive
• Prior to tirzepatide therapy, have a BMI of ≥ 30 kg/m2 (obesity) and ≤ 45 kg/m2.
• Have achieved at least 15% weight loss on tirzepatide therapy at Visit 7 (Participants in Stage 1, who enter the study on tirzepatide, must have a documented pre-tirzepatide weight confirming they have lost at least 15% body weight on tirzepatide)
• Have a history of at least 1 self-reported, unsuccessful, dietary effort to lose body weight
• All female participants of childbearing potential must have a negative urine pregnancy test at screening and a negative urine pregnancy test at study visit 7 prior to study intervention. Postmenopausal females with amenorrhea for at least 2 years will be eligible if they are \> 50 years of age. Postmenopausal females with amenorrhea for at least 2 years, who are ≤ 50 years, must also have documented serum follicle stimulating hormone levels \> 35 mUI/mL
• Able to walk at least 400 yards (roughly the distance of a track) and climb a flight of stairs without difficulty due to either musculoskeletal injuries/diseases or cardiopulmonary diseases
• If sexually active, WOCBP must use one of the following birth control methods during the entire course of the study as specified:
• Intrauterine device in place for at least 3 months before the first dose of tirzepatide and throughout the study
• Barrier method (condom, diaphragm) with spermicide for at least 14 days before the first dose of tirzepatide and throughout the study
• Surgical sterilization of the male partner(s) (vasectomy for at least 6 months before first dose of tirzepatide) or
• Hormonal contraceptives with a barrier method for at least 3 months before the first dose of tirzepatide and throughout the study

You may not qualify if:

• Medical conditions that contraindicate the use of tirzepatide for weight management, as detailed in the tirzepatide prescribing information
• BMI ≥ 40 kg/m2 at Visit 7
• Females who are or intend to be pregnant or breastfeeding during the study
• Known serious hypersensitivity to tirzepatide or any of the excipients in tirzepatide
• History of infectious liver disease excluding recovered Hepatitis A infection
• History of pancreatitis within 6 months of screening or any prior history of recurrent pancreatitis (i.e., two or more episodes of pancreatitis)
• Potentially unreliable participants or those judged by the investigator to be unsuitable for the study
• Unable or unwilling to follow the dietary restrictions specified by the clinical protocol
• Known history of or active binge eating disorder or suspected binge eating disorder based on binge eating disorder assessment questionnaire
• Known history of or active substance abuse including alcohol within the past 2 years that, in the opinion of the investigator, may preclude the participant from following the protocol and completing the study
• Have history of use of marijuana or tetrahydrocannabinol (THC)-containing products within 3 months of screening or unwillingness to abstain from marijuana or THC-containing products use during the study
• Diabetes-related conditions:
• History of type 1 or type 2 diabetes (T2D) or screening values consistent with T2D, or history of any genetic form of diabetes
• HbA1c \> 6.5% or fasting glucose \> 125 mg/dL consistent with T2D diagnosis according to the American Diabetes Association Standards of Care 2024 (Participants with isolated impaired fasting glucose \[100 to 125 mg/dL, inclusive\] may enroll in the study)
• Laboratory values or clinical abnormalities:

Sponsors & Collaborators

• Fractyl Health Inc.: lead

Study Sites (32)

Helios Clinical Research

Phoenix, Arizona, 85028, United States

Location

Honor Health

Scottsdale, Arizona, 85258, United States

Location

Hoag Hospital

Newport Beach, California, 92663, United States

Location

UCLA Santa Monica Medical Center

Santa Monica, California, 90095, United States

Location

Zenith Clinical Research

Hollywood, Florida, 33021, United States

Location

Nature Coast Clinical Research

Inverness, Florida, 32162, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

Encore Borland-Groover Clinical Research

Jacksonville, Florida, 32256, United States

Location

International Research Associates

Miami, Florida, 33183, United States

Location

Advent Health

Orlando, Florida, 32804, United States

Location

K2 Medical Research South Orlando

Orlando, Florida, 32806, United States

Location

Orlando Health Weight Loss and Bariatric Surgery Institute

Orlando, Florida, 32806, United States

Location

Synexus Clinical Research Institute - The Villages (AES)

The Villages, Florida, 32162, United States

Location

Metabolic Research Institute

West Palm Beach, Florida, 33401, United States

Location

Cleveland Clinic, Weston

Weston, Florida, 33331, United States

Location

Investigators Research Group, LLC

Brownsburg, Indiana, 46112, United States

Location

American Health Network - Franklin

Franklin, Indiana, 46131, United States

Location

American Health Network - Greenfield

Greenfield, Indiana, 46140, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

American Health Network - Muncie

Muncie, Indiana, 47304, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

NYC Research, Inc. (Endocrine Associates of West Village)

Long Island City, New York, 11106, United States

Location

NYU-Langone

New York, New York, 10016, United States

Location

Preferred Primary Care Physician Pittsburgh

Pittsburgh, Pennsylvania, 15243, United States

Location

Preferred Primary Care Physician

Pittsburgh, Pennsylvania, 15326, United States

Location

Preferred Primary Care Physician

Uniontown, Pennsylvania, 15401, United States

Location

Baylor St. Luke's Medical Center

Houston, Texas, 77030, United States

Location

Juno Research, LLC

Houston, Texas, 77040, United States

Location

Simcare Medical Research LLC

Sugar Land, Texas, 77478, United States

Location

University of Washington, Seattle

Seattle, Washington, 98109, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

MeSH Terms

Conditions

Obesity; Body-Weight Trajectory; Body Weight Changes; Overweight; Body Weight

Condition Hierarchy (Ancestors)

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

Study Officials

• Shelby Sullivan, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Both the obesity research center team (obesity specialist/endocrinologist, blinded study coordinator, obesity research study staff) and the study participant are blinded to the treatment through the 48-week follow-up visit. The Sponsor (except for unblinded Sponsor personnel \[see below\]) is blinded to the treatment through the 24-week follow-up visit.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, Double-Blind, Sham-Controlled, Multicenter

Study Record Dates

• First Submitted: June 25, 2024
• First Posted: July 3, 2024
• Study Start: September 1, 2024
• Primary Completion (Estimated): February 15, 2027
• Study Completion (Estimated): February 26, 2027
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (32)