Evaluation of Health Improvement in Obese Patients With Obesity-related Comorbidities Followed by EndoZip Procedure

study will include up to 45 (up to 30 patients per site), ages of 21 -75 of obese patients (BMI 30-40 kg/m²) who failed to reduce weight with non-surgical weight-loss methods.

At least 50% of the population included in the study diagnosed with Type 2 diabetes (T2D), and with HbA1c < 9 at least 6 months prior to study enrollment, excluding Insulin-dependent and / or At least 50% of the population included in the study diagnosed with hypertension, treating with 2 or more antihypertensive medications and are well control at least 6 months prior to study enrollment.

The duration for each participant will be 12 months and will include the following follow up visits and procedures:

• Office visits: screening, procedure day, 1 week, and 1, 2, 4, 6, 8, 10, and 12 month(s)
• Remote follow up (by Phone): 3, 5, 7, 9, and 11 month(s)
• Endoscopy: procedure day and 2 months
• Electrocardiogram (ECG) test: Screening and procedure day
• FibroScan test: Screening, 6 and 12 months
• 24- hours Home Ambulatory Blood Pressure Monitor (ABPM), only for patients diagnosed with hypertension: Screening, 6 and 12 months
• Laboratory tests including: (1) Hematology blood tests, (2) Biochemistry blood tests for: sugar Metabolism, liver, proteins, and lipid (3) Urinalysis (Dipstick) tests: Screening, 6 and 12 months.
• Physical examination (include at minimum examination of: GI, Cardiopulmonary, Hepatobiliary and extremities systems) - Screening and procedure day.
• Vital signs (blood pressure and heart rate - supine, pulse, body temperature, respiratory rate (RR) and SpO2): Screening, procedure day, 1 week, 1, 2, 4, 6, 8, 10 and 12 months
• BMI and Waist circumference: Screening, procedure day, 1 week, 1, 2, 4, 6, 8, 10 and 12 months
• Meeting with dietitians / lifestyle modifications counseling: at all follow up office and remote visits:

• Office visit: Screening, procedure day, 1 week, 1, 2, 4, 6, 8, 10 and 12 months
• Remote follows up (phone calls) at months 3,5,7,9, and 11.
• IWQOL-Lite: Screening, 2, 6 and 12 months
• PHQ-9: Screening
• Pregnancy test (only for the relevant population): Procedure day

The patient will required to follow a specific diet and to have a physical activity during the study period ( 12 month).

Inclusion criteria

• Age 21-75
• BMI ≥ 27 and ≤40 kg/m².
• Willingness to comply with the substantial behavioral modifications and dietary restrictions as required by the procedure.
• Patients with history of failure with non-surgical weight-loss methods.
• Willingness to follow protocol requirements, including signed informed consent, routine follow-up schedule, completing laboratory tests, completing IWQOL questionnaire and completing the medically supervised diet and behavior modification program.
• Ability to give informed consent.
• Women of childbearing potential (i.e., not post-menopausal or surgically sterilized) must agree to use adequate birth control methods.
• At least 50% of the population included in the study diagnosed with Type 2 diabetes (T2D), and with HbA1c < 9 at least 6 months prior to study enrollment, excluding Insulin-dependent.
• At least 50% of the population included in the study diagnosed with hypertension, treating with 2 or more antihypertensive medications and are well control at least 6 months prior to study enrollment.

Exclusion criteria

• Prior surgery of any kind on the gastrointestinal tract (except uncomplicated cholecystectomy or appendectomy).
• Patients with history of small bowel or colonic obstruction, and/or adhesive peritonitis and/or abdominal adhesions.
• Patients with any inflammatory disease
• Patients with history of cancer in the gastrointestinal tract.
• Potential upper gastrointestinal bleeding conditions such as a history of angioectasias.
• A known gastric mass or gastric polyps > 1 cm in size.
• Patients with TG >500 or LDL >190
• Patients with BP >180 / 110
• A known hiatal hernia > 4cm of axial displacement of the z-line above the diaphragm or severe or intractable gastro-esophageal reflux symptoms while on maximal medical therapy.
• A structural abnormality in the esophagus or pharynx such as a stricture or diverticulum that could impede passage of the endoscope.
• Patient with motility disorders of the GI tract or intractable constipation
• Patients with known coagulation disorder (INR >1.5) or on anticoagulation therapy.
• Type 1 diabetes or Type 2 diabetes with a HgbA1c >9 and/or injectable medications or likely requiring insulin treatment in the following 12 months.
• Patients with any serious health condition unrelated to their weight that would increase the risk of endoscopy
• Patients with chronic abdominal pain
• Patients with hepatic insufficiency or cirrhosis (CAB>290 Db/m or Fibrosis score >10 kPa)
• Patients with viral and / or autoimmune hepatitis
• Presence of any other form of chronic liver disease
• Recent (within 12 months) or concomitant use of agents known to cause hepatic steatosis (long-term systemic corticosteroids [>10 days], amiodarone, methotrexate, tamoxifen, tetracycline, high dose oestrogens, valproic acid)
• Any contraindication to liver biopsy
• Recent (within 3 months) change in dose/regimen or introduction of Vitamin E (at a dose of ≥400 IU/day), betaine, s-adenosyl methionine, ursodeoxycholic acid, silymarin or pentoxifylline
• Patients that used an intragastric device for weight loss
• Patients with psychological health questionnaire-9 (PHQ-9) score of 10 or higher.
• Patients receiving daily prescribed treatment with high dose aspirin (> 100mg daily), anti-inflammatory agents, anticoagulants or other gastric irritants or on low dose aspirin and cannot come of medication for a total of 10 days peri procedure.
• Patients with history or current abuse of drugs or alcohol
• Patients who are unable or unwilling to take prescribed Proton Pump Inhibitor (PPI) medication
• Patients who are pregnant or breast-feeding.
• Patients who are taking medications that cause weight loss within the last 6 months
• Patients with Severe cardiopulmonary disease or other serious organic disease which might include known history of coronary artery disease, Myocardial infarction within the past 12 months and / or poorly-controlled hypertension
• Patients are currently on medications that are known to affect gastric emptying, such as anti-seizure or anti-arrhythmic medications and / or poorly-controlled Glycemia
• Patients who are taking corticosteroids, immunosuppressants, or narcotics and cannot come of medication for the study period.