Clinical trial NCT06267391: Safety and Effectiveness of Endoscopic Intestinal Re-Cellularization Therapy in Individuals With Type II Diabetes
Official title: A Multicenter, Randomized, Double-blind, Sham-controlled Study for Assessing the Safety and Effectiveness of Endoscopic Intestinal Re-Cellularization Therapy in Individuals With Type II Diabetes (ReCET Study)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Type 2 Diabetes Mellitus
Type2diabetes
Diabetes Mellitus, Type 2
Diabetes
Type 2 Diabetes
Keywords: Diabetes
Type 2 Diabetes
Duodenal Mucosal Resurfacing
Lead sponsor: Endogenex, Inc.
Sponsor class: INDUSTRY
First posted: 2024-02-20
Enrollment: 264
Sex: ALL
Minimum age (years): 22
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The participants randomized in a 2:1 ratio to the ReCET treatment arm or the sham control arm.
Primary purpose: TREATMENT

Brief summary: This study is designed to evaluate the safety and effectiveness of endoscopic intestinal re-cellularization therapy in individuals with type 2 diabetes (T2D) inadequately controlled on non-insulin glucose-lowering medications.

Detailed description: This is a prospective, multi-center, randomized, double-blind, sham-controlled, adaptive study enrolling individuals with type 2 diabetes inadequately controlled on non-insulin glucose-lowering medications. Participants will be randomized to receive the ReCET therapy or sham procedure consisting of device insertion without treatment. Participants will be followed for 6 months for the primary endpoint and 12 months in total. After 12 months, participants randomized to the sham arm may cross-over to receive the ReCET procedure.

Eligibility criteria: Inclusion Criteria:

* 22- 70 years of age, inclusive.
* T2D diagnosis for at least 6 months.
* HbA1C of 7.5-10.5%, inclusive, determined by the central laboratory.
* BMI 27-40 kg/m2, inclusive.
* On 2-4 non-insulin glucose lowering mediations or on monotherapy with either GLP-1 or GLP-1/GIP medications, with no changes in medication or dosing for at least 12 weeks prior to the baseline visit.
* Individualized metabolic surgery (IMS) score ≤ 95.
* Weight stability (≤5% weight change) for at least 12 weeks prior to the screening visit.
* Agree not to donate blood during participation in the study.
* Able to comply with study requirements and understand and sign the Informed Consent Form.
* Women of childbearing potential must be not pregnant and using an acceptable method of contraception throughout the study.
* Willing and able to comply with study visits and study tasks as required per protocol.

Exclusion Criteria:

* Diagnosed with type 1 diabetes.
* History of diabetic ketoacidosis or hyperosmolar nonketotic coma.
* Fasting serum C-peptide \<1 ng/mL (333pmol/l).
* Current use of insulin, or previous use of any types of insulin for \>1 month at any time (except for treatment of gestational diabetes) in last 2 years.
* Hypoglycemic unawareness.
* History of ≥1 severe hypoglycemia episode in past 6 months
* Discontinuation of a GLP-1RA or a GLP-1/GIP dual-agonist within 6 months of the screening visit following at least one month of treatment.
* Known autoimmune disease, including but not limited to, celiac disease, or pre-existing symptoms of systemic lupus erythematosus, scleroderma or other autoimmune connective tissue disorder, or as evidenced by a positive anti-glutamic acid decarboxylase (GAD) test.
* Previous GI surgery that has changed GI anatomy or could limit treatment of the duodenum, such as Billroth 2, Roux-en-Y gastric bypass, gastric band or other similar procedures or conditions.
* Known history of a structural or functional disorder of the upper GI tract that may impede passage of the device through the upper GI tract or increase risk of tissue damage during an endoscopic procedure, including eosinophilic esophagitis, stricture/stenosis, varices, diverticula, or other disorder of the esophagus, stomach and duodenum.
* History of gastroparesis.
* Acute gastrointestinal illness in the last 7 days.
* Known history of irritable bowel syndrome, radiation enteritis or other inflammatory bowel disease, such as Crohn's disease and Celiac disease.
* History of chronic or acute pancreatitis.
* Active hepatitis or active liver disease, or alanine aminotransferase (ALT) level \>3.0 times the upper limit of normal (ULN) for the reference range, as determined by the central laboratory at screening visit. Patients with NAFLD are eligible if their ALT level is ≤3.0 times the ULN.
* Current use of vitamin K antagonists, such as warfarin, or current use of direct-action oral anticoagulants (DOCAs) that cannot be safely discontinued periprocedurally.
* Current use of P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) that cannot be discontinued for 7 days before the procedure.
* Unable to discontinue non-steroidal anti-inflammatory drugs (NSAIDs) from treatment through 4 weeks following the procedure. Alternative use of acetaminophen and low dose aspirin is allowed.
* Use of systemic glucocorticoids (excluding topical or ophthalmic application or inhaled forms) for more than 10 consecutive days within 12 weeks prior to the screening visit.
* Use of medications known to affect GI motility (e.g. metoclopramide/ Reglan)
* Current use of weight loss medications such as Saxenda \[liraglutide \], Xenical® \[orlistat\], Acutrim® \[phenylpropanolamine\], Sanorex® \[mazindol\], Adipex® \[phentermine\], BELVIQ® \[lorcaserin\], Qsymia® \[phentermine/topiramate combination\], Contrave® \[naltrexone/bupropion\], or other weight loss medications including over-the-counter \[OTC\] medications \[for example, Allī®\]) or have discontinued weight loss medications within 6 months.
* Participation in any structured weight loss program or endoscopic weight loss intervention within 6 months of the screen visit.
* Persistent anemia, defined as hemoglobin \<10 g/dL.
* Known history of hemoglobinopathy, hemolytic anemia or sickle cell anemia, or any other traits of hemoglobin abnormalities known to interfere with the measurement of HbA1c.
* History of blood donation or transfusion within 3 months prior to the Screening Visit.
* Unstable or paroxysmal cardiac arrhythmia.
* Any of the following cardiovascular conditions within 6-months prior to screening visit: acute myocardial infarction, cerebrovascular accident (stroke), hospitalization due to congestive heart failure.
* History of valvular heart disease or chronic heart failure (NYHA III or IV).
* Estimated glomerular filtration rate (eGFR) ≤ 45 ml/min/1.73m2 calculated by CKD-EPI Creatinine Equation as determined by the central laboratory.
* Known immunocompromised status, including but not limited to individuals who have undergone organ transplantation, chemotherapy, or radiotherapy within the past 12 months, who have clinically significant leukopenia, who are positive for the human immunodeficiency virus (HIV) or whose immune status makes the participant a poor candidate for clinical trial participation in the opinion of the investigator.
* History of secondary hypothyroidism or inadequately controlled primary hypothyroidism (TSH value outside the normal range at screening).
* Presence of any implanted electronic devices that cannot be turned off during the procedure
* Presence of duodenal or biliary stents.
* Not a candidate for upper GI endoscopy or general anesthesia.
* Active illicit substance abuse or alcoholism (\>2 drinks/day regularly).
* Active malignancy within the last 5 years (excluding non-melanoma skin cancers).
* Women who are breastfeeding.
* Participating in another ongoing clinical trial of an investigational drug or device.
* Binge eating disorder, or any other mental or physical condition which, in the opinion of the study investigator, makes the participant a poor candidate for clinical trial participation.
* Critically ill or has a life expectancy \<5 years.
* Are investigator site personnel directly affiliated with this study and/or their immediate family member. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.

Primary outcomes:
measure: HbA1c
timeFrame: 6 months post-procedure
Secondary outcomes:
measure: HbA1c
timeFrame: 12 months post-procedure
measure: HbA1c ≤7.0% without requiring rescue medication
timeFrame: 6 months post-procedure
measure: Time-in Range (TIR)
timeFrame: 6 months post-procedure
measure: Total body weight loss (%TBWL)
timeFrame: 6 months post-procedure
measure: Incidence of adverse events
timeFrame: 6 months post-procedure
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Birmingham
country: United States
facility: Central Alabama Research
state: Alabama
city: Gardena
country: United States
facility: Velocity Clinical Research, Gardena
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian - Digestive Health Institute
state: California
city: Panorama City
country: United States
facility: Velocity Clinical Research, Panorama City
state: California
city: Hallandale Beach
country: United States
facility: Velocity Clinical Research, Hallandale Beach
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Miami Beach
country: United States
facility: Quantum Clinical Research
state: Florida
city: Miami
country: United States
facility: Universal Axon Clinical Research LLC
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Ocoee
country: United States
facility: West Orange Endocrinology
state: Florida
city: Orlando
country: United States
facility: Advent Health
state: Florida
city: Orlando
country: United States
facility: Orlando Health
state: Florida
city: West Palm Beach
country: United States
facility: Health Synergy Clinical Research
state: Florida
city: Evanston
country: United States
facility: NorthShore University Health System
state: Illinois
city: Clive
country: United States
facility: Heartland Medical Research, Inc.
state: Iowa
city: West Des Moines
country: United States
facility: Iowa Diabetes and Endocrinology Research Center
state: Iowa
city: Baltimore
country: United States
facility: John Hopkins
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Camden
country: United States
facility: Cooper Health System
state: New Jersey
city: New Brunswick
country: United States
facility: Robert Wood Johnson Medical School
state: New Jersey
city: Columbus
country: United States
facility: The Ohio State University- Wexner Medical Center
state: Ohio
city: Austin
country: United States
facility: Velocity Clinical Research - Austin
state: Texas
city: Austin
country: United States
facility: Dell Medical School
state: Texas
city: Austin
country: United States
facility: IMA Clinical Research - Austin
state: Texas
city: Bellaire
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Dallas
country: United States
facility: Velocity Clinical Research, Dallas
state: Texas
city: Dallas
country: United States
facility: Southwest Medical Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical School - William P. Clements Jr. University Hospital
state: Texas
city: DeSoto
country: United States
facility: Epic Medical Research
state: Texas
city: Houston
country: United States
facility: Houston Methodist Research Institute
state: Texas
city: Houston
country: United States
facility: Juno Research, LLC
state: Texas
city: Round Rock
country: United States
facility: Texas Diabetes & Endocrinology, P.A.
state: Texas
city: San Antonio
country: United States
facility: Diabetes & Glandular Disease Clinic, P.A.
state: Texas
city: San Antonio
country: United States
facility: IMA Clinical Research - San Antonio
state: Texas
city: Sugar Land
country: United States
facility: Mt. Olympus Medical Research
state: Texas
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Double Bay
country: Australia
facility: The BMI Clinic
state: New South Wales
city: Saint Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Box Hill
country: Australia
facility: Eastern Health - Box Hill Hospital
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Baker Heart and Diabetes Institute
state: Victoria
Study officials:
affiliation: lcunningham@endogenex.com
name: Lian Cunningham, MD, PhD
role: STUDY_DIRECTOR
References: