Trial Investigating Efficacy of G-POEM

Study Overview
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Brief Summary
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The goal of this randomized sham-controlled trial is to ivestigate efficacy and safety of G-POEM in treatment of diabetic gastroparesis and explore impact of G-POEM on glucose metabolism and incretine hormones.

Detailed Description
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Study Design The study is a single-centre double-blinded sham-controlled randomized trial. All patients have the same baseline characterization. Patients and researchers will be blinded to allocation in trial. Before randomization patients will have an additional meal test performed addressing metabolic characterization of the incretine hormones at baseline. Patients will afterwards be allocated to either the group receiving G-POEM or to the control group where a sham procedure consisting of a gastroscopy with biopsy during general anaesthesia will be done. The randomization will be carried out per-operatively. A computer-generated bloc randomization with sizes of four will be applied. The study will consist of 5 study visits, with a follow-up of 90 days after procedure. Symptoms and adverse event will be monitored 7, 30, and 90 days after intervention. During the 90-day follow-up all primary and secondary outcome will be reassessed. G-POEM procedure is carried out in general anaesthesia in the operating theatre at the Department of Surgery, Hvidovre Hospital. Procedures will be performed by experienced surgeons from the Gastro Unit at Hvidovre Hospital,who postoperatively will have no contact with the research team or study participants. Patients will receive the same care during hospitalization. Patients allocated to sham procedure will have 4 mucosa biopsies from antrum. All biopsies will be handled with formalin and transported to Zealand University Hospital. Here they will be formalin fixed paraffin-embedded and kept in a biobank.

Official Title
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Randomized Sham-controlled Trial Investigating Efficacy of Gastric Peroral Endoscopic Myotomy in Treatment of Diabetic Gastroparesis

Conditions
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Gastroparesis With Diabetes Mellitus

Intervention / Treatment
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* Procedure: G-POEM
* Procedure: Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The ability to give signed written informed consent, Patients with diabetes and gastroparesis, Age >18 years, Gastroparesis is diagnosed with technetium-scintigraphy, Normal gastroscopy, Exclusion Criteria: Ongoing cancer treatment or other concurrent illness that will make the patient unable to attend the study on the discretion of the investigator, Recent gastrointestinal surgery, Active duodenal/gastric ulcer disease, Diseases in the ventricle or previously complicated upper abdominal surgery, Previous bariatric surgery, Pregnancy or breastfeeding, Parkinson disease, Persons who, in the judgement of the investigator, may be unable to follow the protocol, Use of metoclopramide, domperidone, prucalopride, ghrelin, macrolide antibiotics (eg, azithromycin, clarithromycin, erythromycin) during study period. drugs with an anti-cholinergic mechanism, Use of motility slowing agents: anticholinergic agents, calcium channel blockers, TCA, GLP-1 analogs, Lithium, diphenhydramin, glucagon, dopamine agonists, progesterone, L-dopa, calcitonine, octreotide, interferon alfa, sucralsulfate, botulinum toxin injections (eg, Botox®) by pyloric injection less than 4 months prior to procedure

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be allocated to either the group receiving G-POEM or to the control group where a sham procedure consisting of a gastroscopy with biopsy during general anaesthesia will be done. The randomization will be carried out per-operatively. A computer-generated bloc randomization with sizes of four will be applied.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: G-POEM procedure<br>Gastric peroral endoscopic myotomy | Procedure: G-POEM<br>* An Endoscopic submucosal tunnel is formed and extended to the first part of the duodenum, followed by a pyloromyotomy, beginning approximately two centimetres proximal to the pylorus and ending in the first part of duodenum.<br>|
| Placebo Comparator: Sham procedure<br>sham endsocopy with biopsy | Procedure: Sham<br>* Endoscopy is performed and tissue samples are collected from fundus and antrum as part of the Sham procedure<br>* Other names: Endoscopy with tissue sample;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in gastric emptying | assessed by technetium scintigraphy | 90 days after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in gastroparesis cardinal symptom index (GCSI) | patient-rated gastroparesis cardinal symptom index score for gastroparesis-related symptoms (naseau, vomiting, early satiety, postprandial fulness, upper abdominal pain). Range from 0-none to 5-very servere. | 7, 30 and 90 days after intervention. | 
| Changes in Plasma glucose | concentration of plasma glucose in mmol/L | 90 days after intervention. | 
| Changes in postprandial incretinhormones | gastrin, CCK, GIP, GLP-1, GLP-2, glucagon, ghrelin, pancreatic polypeptide (PP) | 90 days after intervention. | 
| Concentration of C-peptide in pmol/L | Concentration of C-peptide in pmol/L | 90 days after intervention. | 
| Changes in continuous glucose | Measure of 10-days interstitial glucose levels with a Dexcom monitor device attached to the abdominal skin | 90 days after intervention. | 
| Incidence of Treatment-Emergent Adverse Events rated by the ASGE lexicon for adverse events | rate and severity of adverse events rated by the ASGE lexicon for adverse events | 7,30 and 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gastroparesis, G-POEM, gastric peroral endoscopic myotomy, technetium-scintigraphy