G-POEM for Glycemic Control in Diabetic Gastroparesis

Official title

Randomized Controlled Clinical Trial Evaluating the Effect of Endoscopic Pyloromyotomy Via Gastric POEM on Glycemic Control in Patients With Diabetes and Gastroparesis

Overview

Gastroparesis, commonly caused by diabetes, affects 30-50% of diabetic individuals and complicates glycemic control due to its bidirectional relationship with blood glucose levels. Current treatments are often ineffective. G-POEM, a minimally invasive endoscopic technique, has demonstrated promising results in improving digestive symptoms, particularly in diabetic patients, with over 80% success. However, its impact on glycemic control has not yet been investigated, highlighting the need for further research.

Detailed description

Gastroparesis is a condition characterized by delayed gastric emptying, resulting in various digestive symptoms. Diabetes is the leading global cause of gastroparesis. This complication affects approximately 30-50% of individuals with diabetes, typically appearing after many years of disease progression and frequently in the presence of other vascular complications. It is associated with autonomic neuropathy and hyperglycemia.

The bidirectional relationship between gastric emptying and blood glucose levels contributes to the complexity of diabetes management, increasing the risk of both postprandial hypoglycemia and delayed hyperglycemia. Existing treatments, including prokinetic and antiemetic medications, are often poorly tolerated and of limited efficacy.

G-POEM (Gastric Per Oral Endoscopic Myotomy) is an endoscopic technique designed to treat refractory gastroparesis by targeting pyloric muscle hypertonicity. This procedure has demonstrated favorable outcomes in approximately two-thirds of cases and presents a favorable safety profile. The diabetic population appears to benefit most from this intervention, with over 80% reporting symptom improvement. To date, no study has evaluated the impact of G-POEM on glycemic parameters in patients with diabetic gastroparesis. This clinical trial aims to address this knowledge gap.

Interventions

• Procedure Immediate G-POEM
  Gastric POEM (G-POEM) performed under general anesthesia. A submucosal tunnel will be created along the greater curvature of the stomach to access the pyloric muscle under endoscopic vision. The pylorus will be incised at two locations with a dual myotomy between the 5 and 8 o'clock positions on the clock face
• Procedure Delayed G-POEM
  Participants will receive standard medical treatment, including prokinetic agents, antiemetics (ondansetron 8 mg twice daily), nutritional support, and dietary counseling. Laxative treatments will be prescribed as needed. After three months, participants will undergo G-POEM as described above

Primary outcome measures

• Percentage of time spent in target glycemic range >10% [Time frame: 3 months after randomization]

Secondary outcome measures (12)

• HbA1c Level [Time frame: 15 days, 3 months, and 6 months after randomization]
• Time in Hypoglycemia (<70 mg/dL) [Time frame: 15 days, 3 months, and 6 months after randomization]
• Time in Hypoglycemia (<54 mg/dL) [Time frame: 15 days, 3 months, and 6 months after randomization]
• Time in Hyperglycemia (>180 mg/dL) [Time frame: 15 days, 3 months, and 6 months after randomization]
• Time in Hyperglycemia (>250 mg/dL) [Time frame: 15 days, 3 months, and 6 months after randomization]
• Mean Glucose Level (mg/dL) [Time frame: 15 days, 3 months, and 6 months after randomization]
• Coefficient of Variation (CV) of Glucose (%) [Time frame: 15 days, 3 months, and 6 months after randomization]
• Gastric Emptying Assessment [Time frame: 15 days, 3 months, and 6 months]
• Fundic Accommodation Ratio [Time frame: 15 days, 3 months, and 6 months]
• Gastroparesis Symptom Severity (GCSI Score) [Time frame: 15 days, 3 months, and 6 months]
• Severity of Upper GI Symptoms (PAGI-SYM Score) [Time frame: 15 days, 3 months, and 6 months]
• Gastrointestinal Quality of Life (GIQLI Score) [Time frame: 15 days, 3 months, and 6 months]

Eligibility criteria

Inclusion criteria

• Aged 18 to 90 years;
• Diagnosed with diabetes for at least 5 years and be treated with optimized insulin therapy;
• Severe gastroparesis with gastric retention >20% at 4h (confirmed by scintigraphy);
• Failure of conventional gastroparesis treatment;
• Continuous glucose monitoring (CGM) in use or willingness to use during study
• Time in range (70-180 mg/dL) <70%

Exclusion criteria

• Are treated with an automated insulin therapy system (closed-loop);
• Have previously undergone gastric neurostimulation therapy with Enterra (Medtronic ©);
• Have been treated with erythromycin in the past three months;
• Do not provide informed consent;
• Are pregnant or breastfeeding during the study period;
• Are under legal guardianship;
• Have contraindications to the POEM procedure, including contraindications to anesthesia and/or active anticoagulation that cannot be paused;
• Have severe chronic constipation, defined by a Cleveland score >15 (Agachan et al., Dis Colon Rectum, 1996);
• Have a history of esophagogastric surgery (excluding anti-reflux surgery), including esophagogastric resection or any type of bariatric surgery;
• Have chronic intestinal pseudo-obstruction;
• Have a clinical suspicion of chronic mesenteric ischemia, indicated by severe malnutrition, postprandial pain, and signs of digestive atherosclerosis;
• Refuse to share CGM data via the Libre Link platform;
• Plan or undergo changes in antidiabetic therapy or insulin delivery systems during the study period;
• Are being treated with any gastric-emptying delaying agents, including GLP-1 receptor agonists;
• Are undergoing treatment with ascorbic acid during the study;
• Have not previously attempted therapy with at least one prokinetic drug;
• Are actively treated with opioids;
• Have had prior pyloromyotomy or pyloroplasty;
• Have known eosinophilic gastroenteritis;
• Have an organic obstruction of the pylorus or intestinal tract (e.g., fibrotic stenosis);
• Have a severe coagulopathy;
• Have esophageal or gastric varices and/or portal hypertension gastropathy;
• Have decompensated liver cirrhosis (Child B or Child C);
• Have an active gastroduodenal ulcer;
• Have active cancer or precancerous conditions of the stomach or duodenum (dysplasia, gastric cancer, GIST).
• Have a known medical condition that, in the investigator's opinion, could interfere with the study protocol;
• Have experienced diabetic ketoacidosis requiring hospitalization within six months prior to enrollment;
• Have had a severe hypoglycemic episode requiring hospitalization within six months prior to enrollment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06965543 · SFED-166

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗