Magnetic Compression Anastomosis Procedure for Partial Jejunoileal Anastomosis: Assessing the Viability of an Innovative Metabolic Approach

Title: Magnetic Compression Anastomosis Procedure for Partial Jejunoileal Anastomosis: Assessing the Viability of an Innovative Metabolic Approach Protocol Number 2025/01/EDIT Trial Type Investigator Initiated Trial This investigator-initiated trial (IIT) is a prospective, single-center, single-arm observation study in patients designed to explore metabolic indicator and procedural outcomes in patients with T2DM. A total of 5 patients with T2DM will be recruited in the study. Following the administration of general anesthesia, surgeon will introduce the ring component of the magnetic compression anastomosis system through an enterotomy. The insertion of the distal ring into the terminal ileum via an enterotomy, positioned approximately 30 cm proximal to the ileocecal valve, utilizing a laparoscopic deployment instrument. The proximal ring is then placed in the proximal jejunum, located around 20 cm (with a variance of ± 10 cm) distal to the ligament of Treitz. Laparoscopic techniques are employed to maneuver the bowel, aligning the proximal and distal magnets for effective magnetic coupling and observing the ring pair mating via intraoperative imaging (fluoroscopy or plain x-ray). This IIT will be conducted in single centre in India by a qualified investigator. It will be initiated after Institutional Review Board (IRB)/Independent Ethics Committee (IEC).

The anticipated timeline for this study is as follows:

• Study Participant Enrollment: 02 months
• Procedure Period: 01 day
• Post procedure care: As suggested by the PI
• Safety and functionality follow-up: 6 weeks, 3 months, 6 months, 9 months
• Additional indications of efficacy follow-up: 12 months

Inclusion criteria

• Subjects will be included in the study if they meet the following criteria:

• Participant is willing and able to give informed consent for participation in the study.
• Male or Female, aged ≥ 25 years to ≤ 65 years.
• BMI greater than or equal to 25 and less than 50
• Clinical diagnosis of T2DM by plasma glucose criteria, either the fasting plasma glucose (FPG) value or the 2-h plasma glucose (2-h PG) value during a 75-g oral glucose tolerance test (OGTT), or A1C criteria
• Glycated Hemoglobin greater than or equal to 7.5% and less than 10.5% in at least one laboratory analysis conducted within the past 3 months, typically associated with a recommendation by patient's primary care physician and/or endocrinologist for intensification of treatment beyond oral medications
• Currently taking oral combination therapy for T2DM
• At least 12 months of experience with Diabetes Self-Management and Support

Exclusion criteria

• 1. Pregnancy or breastfeeding mothers, or individuals planning to become pregnant in next 9-12 months 2. Vulnerable individuals (mentally disabled, physically disabled, prisoner, etc.) 3. Current enrolment in another research study or previous participation within 30 days of enrolment 4. Current history of injected Glucagon Like Peptide 1 (GLP1) 5. American Society of Anesthesiologists (ASA) physical classification level of 4 or greater 6. Hypoglycemia unawareness or a history of severe hypoglycemia (more than 1 severe hypoglycemic event, as defined by need for third-party-assistance, in the last year) 7. Evidence of type 1 diabetes or of pancreatic exhaustion, as indicated by a C peptide fasting level less than 1 or, for type 1 diabetes, based on measurable levels of serum anti-GAD-65 autoantibodies or, at investigator's discretion, based on measurable levels of other T1D-associated autoantibodies 8. History of highly unusual or challenging gastrointestinal tract anatomy ascertained through earlier endoscopic examination or other diagnostic imaging 9. History of (or known to be at prohibitive risk for) any of the following diseases of the small bowel or closely related conditions: Crohn's disease or other inflammatory bowel disease, celiac disease, resection for cancer, or intra-abdominal adhesive disease including intussusception, perforated appendix and Meckel's diverticulum 10. History of small bowel surgery such as small bowel resection 11. Active H. pylori infection (prospective participants with active H. pylori may continue with the screening process if they are treated via medication and re-testing verifies the condition has resolved.) 12. History of chronic or acute pancreatitis 13. Known active hepatitis or active liver disease 14. Symptomatic gallstones or kidney stones or acute cholecystitis

Subjects will be deemed ineligible to participate if they fulfill any of the following criteria:

• Pregnancy or breastfeeding mothers, or individuals planning to become pregnant in next 9-12 months
• Vulnerable individuals (mentally disabled, physically disabled, prisoner, etc.)
• Current enrolment in another research study or previous participation within 30 days of enrolment
• Current history of injected Glucagon Like Peptide 1 (GLP1)
• American Society of Anesthesiologists (ASA) physical classification level of 4 or greater
• Hypoglycemia unawareness or a history of severe hypoglycemia (more than 1 severe hypoglycemic event, as defined by need for third-party-assistance, in the last year)
• Evidence of type 1 diabetes or of pancreatic exhaustion, as indicated by a C peptide fasting level less than 1 or, for type 1 diabetes, based on measurable levels of serum anti-GAD-65 autoantibodies or, at investigator's discretion, based on measurable levels of other T1D-associated autoantibodies
• History of highly unusual or challenging gastrointestinal tract anatomy ascertained through earlier endoscopic examination or other diagnostic imaging
• History of (or known to be at prohibitive risk for) any of the following diseases of the small bowel or closely related conditions: Crohn's disease or other inflammatory bowel disease, celiac disease, resection for cancer, or intra-abdominal adhesive disease including intussusception, perforated appendix and Meckel's diverticulum
• History of small bowel surgery such as small bowel resection
• Active H. pylori infection (prospective participants with active H. pylori may continue with the screening process if they are treated via medication and re-testing verifies the condition has resolved.)
• History of chronic or acute pancreatitis
• Known active hepatitis or active liver disease
• Symptomatic gallstones or kidney stones or acute cholecystitis
• 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 warfarin) which cannot be discontinued for 7 days before and 14 days after the procedure
• Use of P2Y12 inhibitors (clopidogrel, pasugrel, ticagrelor) which cannot be discontinued for 14 days before and 14 days after the procedure (use of low-dose aspirin allowable)
• History of serious complications of T2DM including coronary artery disease, hypertension, peripheral vascular disease, diabetic retinopathy, and/or diabetes-related soft tissue infection
• 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
• Persistent anemia, defined as Hgb<10 g dL-1
• Estimated Glomerular Filtration Rate (eGFR) or Modified of Diet in Renal Disease (MDRD) <30 ml/min/1.73m2
• Active systemic infection
• Currently on anticoagulation therapy other than a low-dose aspirin regimen
• Chemotherapeutic cancer treatment within past 9 months, history of abdominal radiation, or active malignancy within the past 5 years
• Active illicit substance abuse or alcoholism
• Known sensitivity to possible medications used before, during, or after the Connect procedure, including but not limited to the following: sedative agents, general anesthetics, topical anesthetics, and opioid analgesics
• Any other serological markers likely to be associated with poor outcomes