RESET System Pivotal Trial (Rev F)

Официальное название

A Randomized, Multi-Center, Pivotal Efficacy and Safety Study Evaluating the RESET® System for Glycemic Improvement in Patients With Inadequately Controlled Type 2 Diabetes and Obesity

Обзор

A Randomized, Multi-Center, Pivotal Efficacy and Safety Study Evaluating the RESET System for Glycemic Improvement in Patients with Inadequately Controlled Type 2 Diabetes and Obesity, the STEP-1 Study. A multi-center, double-blinded, randomized, sham-controlled trial to evaluate the safety and effectiveness of the RESET System plus moderate intensity lifestyle and dietary counseling compliant with 2024 ADA Standard of Care as compared to a sham control receiving moderate intensity lifestyle and dietary counseling. Both the treatment and sham group will practice medical management compliant with STEP-1 Study Guidelines. Patients will be randomized 3 (RESET):1 (Sham).

Подробное описание

The objective of this study is to evaluate the safety and effectiveness of the RESET System when used with moderate intensity lifestyle and dietary counseling and medical management, in patients with baseline HbA1c ≥ 7.5% and ≤10%, and BMI ≥ 30 kg/m2 and ≤ 50kg/m2, whose diabetes medications consist of at least dual therapy for 3 months, yet have not achieved adequate HbA1c control (\<7%).

Specific objectives of this study are:

1. To determine if the RESET System significantly improves glycemic control 2. To determine that the RESET System can be safely used to improve glycemic control

Вмешательства

• Устройство RESET Liner
  The RESET System is provided as a single-use, sterile device and consists of an RESET Liner preloaded, packaged and sterilized within the RESET Delivery System. The RESET Delivery System is utilized to deliver the RESET Liner to the proximal small intestine. The RESET Liner is removed using the RESET Retrieval System. The RESET System incorporates no pharmacological, biological tissue or blood products.
• Другое Sham
  Patient receives upper endoscopy but no treatment

Первичные конечные точки

• Change in HbA1c [Срок оценки: 9 Months]

Вторичные конечные точки (12)

• HbA1c value [Срок оценки: 9 and 21 months]
• Weight Loss [Срок оценки: 9 and 21 months]
• Insulin use [Срок оценки: 9 and 21 months]
• LDL cholesterol [Срок оценки: 9 and 21 months]
• Triglycerides [Срок оценки: 9 and 21 months]
• Blood pressure [Срок оценки: 9 and 21 months]
• Fasting blood glucose level [Срок оценки: 9 and 21 months]
• Vitamin D [Срок оценки: 9 and 21 months]
• Vitamin D Supplementation [Срок оценки: 9 and 21 months]
• Refractory to Vitamin D Supplementation [Срок оценки: 9 and 21 months]
• Serum Creatinine [Срок оценки: 9 and 21 months]
• eGFR [Срок оценки: 9 and 21 months]

Критерии участия

Критерии включения

• Age ≥22 years and ≤ 65 years
• Have understood and signed the approved informed consent form
• Diagnosis of type 2 diabetes
• HbA1c ≥ 7.5% and ≤10%
• BMI ≥30kg/m2 and ≤ 50kg/m2
• Willing and able to comply with study requirements
• Documented negative pregnancy test in women of childbearing potential
• Women of childbearing potential not intending to become pregnant (continue to be on an approved form of birth control) for the duration of their trial participation, including post explant period. Women of child-bearing age without known sterilization will be placed on 1 form of birth-control to prevent unwanted pregnancies
• At least one year of medical records available, including detailed medical therapy and dosing information
• Failed to achieve adequate HbA1c reduction (<7.5%) after dual therapy for at least 3-month stable dosage of diabetes medication(s), including insulin, metformin, SGLT-2 inhibitor, GLP-1 RA, Dual GLP-1/GIPR agonist or, other medications including meglitinides, sulfonylureas, thiazolidinediones, or DPP-4s.

Критерии исключения

• Previous treatment with the RESET System
• Previous GI surgery that could preclude the ability to place the RESET Liner or affect the function of the RESET Liner, or abnormal GI anatomical finding that could preclude the ability to place the RESET Liner or affect the function of the RESET Liner
• Hypoglycemia and/or DKA/HHNK in the last 6 months requiring 3rd party assistance
• Known history of liver disease (e.g., viral or autoimmune etiology, METAVIR grade 2 or higher fibrosis/cirrhosis from a biopsy within the past 6 months, but not including incidental fatty liver)
• eGFR of less than 45 ml/min/1.73 m2
• Prior history of an abscess requiring hospitalization, intravenous antibiotics or drainage
• Previous treatment for severe liver disease and/or biliary tract disease, including but not limited to, surgery, bile duct dilatation, and stent placement
• Diagnosis of type 1 diabetes mellitus or having any history of ketoacidosis
• Fasting C-peptide < 1.0 ng/mL
• Triglyceride level > 600 mg/dL
• Vitamin D deficiency (<20ng/ml)
• Uncorrectable bleeding diathesis, platelet dysfunction, thrombocytopenia with platelet count less than 100,000/microliter, or known coagulopathy
• Height < 5 feet (152.4 cm)
• Current alcohol addiction, current drug addiction or usage, of drugs such as, narcotics, opiates, or benzodiazepines and other addictive tranquilizers
• History of pancreatitis, including gallstone related pancreatitis (subsequent to which patient has cholecystectomy)
• Diagnosis of osteopenia or osteoporosis or currently taking denosumab, romosozumab-aqqg, bisphosphonates or teriparatide
• Diagnosis of autoimmune connective tissue disorder (e.g. lupus erythematosus, scleroderma)
• Active or recent (less than 12 months) gastroesophageal reflux disease (GERD) unless treated with H2RAs not PPI.
• Uncontrolled thyroid disease, including a history of thyroid cancer, hyperthyroidism, or taking thyroid hormone for any reason other than primary hypothyroidism (TSH level must be between 0.4-4)
• Currently taking prescription antithrombotic therapy (e.g. anticoagulant or antiplatelet agent) within 10 days prior to randomization and/or there is a need or expected need to use during the trial 9 months post implant procedure
• Currently taking the following medications (within 30 days prior to randomization) and/or there is a need or expected need to use these medications during the trial 12 months post index procedure:

Restricted Medications/Supplements Systemic corticosteroids Proton Pump Inhibitor (PPI) Drugs known to affect GI motility (e.g.metoclopramide) Prescription or over-the-counter weight loss medication(s) Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), aspirin, ibuprofen, and other anti-inflammatory medication for study duration Medications known to cause significant weight gain or weight loss (e.g. chemotherapeutics)

Supplements that are known or suspected to increase bleeding risk including but not limited to:

Gingko biloba Ginseng Vitamins C \& E Turmeric St. John's wort Evening primrose oil Feverfew Green Tea Extract

• Active H. pylori
• History of Crohn's disease, atresias or untreated stenoses
• Abnormal pathologies or conditions of the gastrointestinal tract, including ulcers or upper gastrointestinal bleeding conditions within 3 months of randomization
• Patients may be disqualified for study inclusion for any condition determined by the PI that places the patient at undue risk
• Poor dentition not allowing complete chewing of food
• Enrolled in another investigational study within 3 months of screening for this study (enrollment in observational studies is permitted)
• Residing in a location without ready access to study site medical resources
• Documented weight loss of 5% total body weight (TBW) anytime during the 3 months preceding randomization
• Positive Fecal Immunochemical Test (FIT) at time of screening
• History or observation of psychological disorder or behavior which could preclude compliance to the treatment and follow up plan
• No access to an active telephone and internet service for provision of Follow Up Schedule calls and electronic diary
• Having donated blood or received a blood transfusion in the 90 days prior to baseline labs. Patients should agree not to donate blood during the study
• Any condition that increases red cell turnover, such as thalassemia
• Existence of (>5 cm string test) Pseudomonas aeruginosa, Stenotrophomonas maltophilia and/or Klebsiella pneumoniae serotype K1 and K2
• A known sensitivity to nickel or titanium
• Do not meet the screening criteria for MRI (i.e., MRI unsafe, or MRI conditional but not appropriate for the region of interest)
• Patients with history or suspicion of coronary artery disease

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 7 центров

• MedStar Health Research Institute — Washington D.C.
• University of Miami Hospital — Miami
• Brigham and Women's Hospital — Boston
• Michigan Medicine, Division of Gastroenterology and Hepatology — Ann Arbor
• Weill Cornell Medicine — New York
• Cleveland Clinic — Cleveland
• Baylor College of Medicine — Houston

Публикации

• Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008 Oct 9;359(15):1577-89. doi: 10.1056/NEJMoa0806470. Epub 2008 Sep 10. PMID 18784090
• Rodbard D. Interpretation of continuous glucose monitoring data: glycemic variability and quality of glycemic control. Diabetes Technol Ther. 2009 Jun;11 Suppl 1:S55-67. doi: 10.1089/dia.2008.0132. PMID 19469679
• Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000 Aug 12;321(7258):405-12. doi: 10.1136/bmj.321.7258.405. PMID 10938048
• Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):854-65. PMID 9742977
• Ford ES, Li C, Little RR, Mokdad AH. Trends in A1C concentrations among U.S. adults with diagnosed diabetes from 1999 to 2004. Diabetes Care. 2008 Jan;31(1):102-4. doi: 10.2337/dc07-0565. Epub 2007 Oct 12. No abstract available. PMID 17934146
• Detournay B, Cros S, Charbonnel B, Grimaldi A, Liard F, Cogneau J, Fagnani F, Eschwege E. Managing type 2 diabetes in France: the ECODIA survey. Diabetes Metab. 2000 Nov;26(5):363-9. PMID 11119015
• Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA. 2003 Jan 1;289(1):76-9. doi: 10.1001/jama.289.1.76. PMID 12503980
• Torquati A, Lutfi R, Abumrad N, Richards WO. Is Roux-en-Y gastric bypass surgery the most effective treatment for type 2 diabetes mellitus in morbidly obese patients? J Gastrointest Surg. 2005 Nov;9(8):1112-6; discussion 1117-8. doi: 10.1016/j.gassur.2005.07.016. PMID 16269382

Идентификаторы

NCT: NCT04101669 · 18-1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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