Endoscopic Application of Pulsed Electric Fields Using the Endogenex Generation 2 System for Duodenal Mucosal Regeneration for EliMination of INsulin in the treatmENT of Type 2 Diabetes: a Randomized Double-blind Sham Controlled Trial to Evaluate Safety, Feasibility and Efficacy Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Incidence rate of procedure-related SAEs, UADEs, SADEs, AESIs [safety]
研究概览
简要总结
The objective of this study is to evaluate the safety, feasibility and efficacy of pulsed electric field induced duodenal mucosal regeneration (with the Endogenex System en Gen 2 Device) combined with a GLP-1 receptor agonist (Semaglutide, Ozempic) in subjects with insulin-dependent type 2 diabetes mellitus.
详细描述
The objective of this study is to evaluate the safety, feasibility and efficacy of pulsed electric field induced duodenal mucosal regeneration (with the Endogenex System en Gen 2 Device) combined with a GLP-1 receptor agonist (Semaglutide, Ozempic) in subjects with insulin-dependent type 2 diabetes mellitus and an adequate beta cell reserve in a randomized sham-controlled study. The aimed effect is an adequate or improved glucose regulation without the need for insulin therapy. Secondary effects include improved cardiovascular, hepatic, and metabolic parameters.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
In this study, both the study team and the study subjects are blinded to the treatment through the 24 week follow-up visit. While the endoscopist is not blinded to individual treatments, he or she is blinded to cohort level data and is not responsible for patient follow-up. At the 24 week visit, the subject and study team are unblinded. The subjects who received the sham treatment undergo a cross-over PEF therapy treatment when no adequate glycemic control.
入排标准
- 年龄范围
- 28 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with type 2 diabetes mellitus
- •28 - 75 years of age
- •On daily long acting insulin dose ≤ 1 U/kg, with a stable dose (within 10%) over 1 month
- •BMI ≥ 24 and ≤ 42 kg/m2
- •HbA1c ≤ 64 mmol/mol (8.0%)
- •Fasting C-peptide ≥ 0.2 nmol/L (0.6 ng/ml)
- •Willing to comply with study requirements and able to understand and comply with signed informed consent
排除标准
- •Diagnosed with Type 1 Diabetes or with a history of ketoacidosis
- •Current use of multiple daily doses insulin or insulin pump.
- •Current or within the last 3 months use of a GLP-1 analogue.
- •Known autoimmune disease, as evidenced by a positive Anti-GAD test, including Celiac disease, or pre-existing symptoms of systemic lupus erythematosus, scleroderma or other autoimmune connective tissue disorder
- •Previous GI surgery that could affect the ability to treat the duodenum such as subjects who have had a Bilroth 2, Roux-en-Y gastric bypass, or other similar procedures or conditions
- •History of chronic or acute pancreatitis
- •Known active hepatitis or active liver disease
- •Symptomatic gallstones or kidney stones, acute cholecystitis or history of duodenal inflammatory diseases including Crohn's Disease and Celiac Disease
- •History of coagulopathy, upper gastro-intestinal bleeding conditions such as ulcers, gastric varices, strictures, congenital or acquired intestinal telangiectasia
- •Use of anticoagulation therapy (such as phenprocoumon and acenocoumarol) which cannot be discontinued for 3-5 days before and 48 hours after the procedure and novel oral anticoagulants (such as rivaroxaban, apixaban, edoxaban and dabigatran) which cannot be discontinued for 48 hours before and 48 hours after the procedure in accordance with the local protocol
- •Use of P2Y12 inhibitors (clopidogrel, pasugrel, ticagrelor) which cannot be discontinued for 5 days before and 48 hours after the procedure in accordance with the local protocol. Use of aspirin is allowed.
- •Unable to discontinue NSAIDs (non-steroidal anti-inflammatory drugs) during treatment through 4 weeks post procedure phase
- •Taking corticosteroids or drugs known to affect GI motility (e.g. Metoclopramide)
- •Receiving weight loss medications such as Meridia, Xenical, or over the counter weight loss medications
- •Anemia, defined as Hgb < 6.2 mmol/l
- •Known history of severe permanent cardiac arrhythmia's with clinical symptoms
- •Significant cardiovascular disease, including known history of valvular disease or myocardial infarction, heart failure, transient ischemic attack, or stroke within 6 months prior to the screening visit
- •With any implanted electronic devices or duodenal metallic implants
- •eGFR or MDRD < 30 ml/min/1.73m^2
- •Active systemic infection
- •Active malignancy within the last 5 years
- •Not potential candidates for surgery or general anesthesia
- •Active illicit substance abuse or alcoholism
- •Pregnancy or wish getting pregnant in next year
- •Participating in another ongoing clinical trial of an investigational drug or device that can interfere with the current study.
- •Any other mental or physical condition which, in the opinion of the Investigator, makes the subject a poor candidate for clinical trial participation
研究组 & 干预措施
PEF therapy procedure
Patients receive endoscopic duodenal PEF therapy, which is performed using the Endogenex device.
After which a 2 week isocaloric diet is followed, and then semaglutide, a GLP-1 receptor agonist is started.
干预措施: PEF therapy using the Endogenex Device (Device)
PEF therapy procedure
Patients receive endoscopic duodenal PEF therapy, which is performed using the Endogenex device.
After which a 2 week isocaloric diet is followed, and then semaglutide, a GLP-1 receptor agonist is started.
干预措施: Semaglutide, 1.0 mg/mL (Drug)
Sham procedure
Patients receive sham procedure, this consists of placing an Endogenex catheter, or a catheter with a similar circumference at the endoscopists discretion in the stomach and leaving it in place for 30 minutes.
After which a 2 week isocaloric diet is followed, and then semaglutide, a GLP-1 receptor agonist is started
干预措施: Semaglutide, 1.0 mg/mL (Drug)
Sham procedure
Patients receive sham procedure, this consists of placing an Endogenex catheter, or a catheter with a similar circumference at the endoscopists discretion in the stomach and leaving it in place for 30 minutes.
After which a 2 week isocaloric diet is followed, and then semaglutide, a GLP-1 receptor agonist is started
干预措施: Sham procedure (Other)
结局指标
主要结局
Incidence rate of procedure-related SAEs, UADEs, SADEs, AESIs [safety]
时间窗: 24 weeks
The incidence rate of procedure-related SAEs, UADEs, SADEs, AESIs 24 weeks post PEF therapy procedure.
Percentage of patients off insulin at 24 weeks [efficacy]
时间窗: 24 weeks
Percentage of patients free of insulin at 24 weeks post PEF therapy with an HbA1c ≤ 58 mmol/mol compared to sham.
次要结局
- Secondary safety endpoint 1 - hypoglycemic events(Through study completion (1 to 1,5 year))
- Secondary safety endpoint 2 - SAEs(Through study completion (1 to 1,5 year))
- Secondary feasibility endpoint 2 - GLP-1RA tolerability(Through study completion (1 to 1,5 year))
- Secondary efficay endpoint 1 - HbA1c 48 weeks(at 48 weeks)
- Secondary feasibility endpoint 1 - technical success rate(24 weeks (after cross-over))
研究者
Jacques J.G.H.M. Bergman
prof. dr.
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)