Multicentric Approval Study Trans-Duodenal Barrier for Typ 2 Diabetes With Obesity

Title of the study Clinical study to investigate the performance and safety of the Trans-Duodenal Barrier (LuST) Short title LuST EUDAMED Single Identification Number (SIN) or CIV-ID To be determined Sponsor Trans-Duodenal Concepts GmbH Tannhäuserring 93 68199 Mannheim Tel georg.kaehler@transduodenal.com Manufacturer Trans-Duodenal Concepts GmbH Tannhäuserring 93 68199 Mannheim Tel Test product Trans-Duodenal Barrier (TDB®) Risk class II b Study director Prof. Dr. Christoph Reißfelder, Director of the University Surgical Clinic Mannheim Other study centers

1. Bamberg Social Foundation - Bamberg Clinic
2. Charité Berlin
3. University Hospital Bochum
4. Dresden Municipal Hospital
5. St. Georg Hospital, Leipzig
6. University Hospital Leipzig
7. University Hospital Mannheim
8. University Hospital Würzburg Statistics and database management pfm medical expert gmbh, Wankelstraße 60, 50996 Cologne Project management

Study contact:

Prof. Dr. Georg Kähler Trans-Duodenal Concepts GmbH Tannhäuserring 93 68199 Mannheim georg.kaehler@transduodenal.com Study design National, multicenter, non-randomized, prospective CE marking study at eight trial sites in Germany.

Data on the use of TDB® will be collected over a period of 28 weeks. The focus here is on the performance of the Trans-Duodenal Barrier as measured by the long-term diabetes value HbA1c, patient satisfaction (patient-reported outcome), and the complication rate.

Compliance with the current Declaration of Helsinki, DIN EN ISO 14155:2021-05, MDR (EU) 2017/745, and MPDG (May 12, 2021)

Study duration Total: 64 weeks Per patient: 28 weeks Recruitment phase: 36 weeks Follow-up examinations: 2, 6, 12, 24, and 28 weeks after implantation

Test product and procedure The TDB® is an endoscopically implantable medical device. The indications for the use of the TDB® are diseases associated with metabolic syndrome, in particular type II diabetes mellitus in conjunction with obesity and non-alcoholic liver disease. The TDB® is used for the endoscopic creation of a temporary reversible bypass situation in the duodenum and upper jejunum. The aim of using the TDB® is to prevent contact and absorption of nutrients in the duodenum and to prolong the feeling of satiety.

Planned number of patients 126 patients

Inclusion criteria

• Obese patients with type 2 diabetes mellitus,
• Age ≥ 18 years,
• The patient is able to understand the nature, significance, and scope of the clinical trial (MPDG §28),
• The patient has been informed and all written consents from the patient are available.

Exclusion criteria

• The patient is mentally incapable of understanding the nature, objectives, or possible consequences of the clinical trial,
• The patient is unwilling or unable to follow postoperative instructions,
• The patient has been placed in an institution by court or official order (MPDG §27),
• The patient lives more than 100 km from the treatment site
• Pregnancy,
• The patient is participating in another clinical trial in the field of diabetes management or metabolic syndrome,
• Known allergies to polyurethanes and/or polyamides and/or methylene blue,
• Coagulation disorders (thrombocytes < 100,000; Quick < 65%),
• Previous surgery in the gastrointestinal tract
• Known adhesions in the abdominal cavity
• Acute gastrointestinal diseases
• Untreated psychosis, bulimia

Examinations

• Age, weight, height of the patient
• Metabolic parameters, HbA1c, satisfaction with diabetes treatment (questionnaire)
• Duration of implantation, technical success
• Incidence and severity of side effects, adverse events with the implant, and unexpected side effects from using the implant
• Medical measures to control them
• Explantation: duration, local findings in the former implant site

Study hypothesis The study hypothesis is that the Transduodenal Barrier will lead to an average reduction in HbA1c of at least 0.8% in six months. Example: HbA1c from 8.5% - 0.8% to 7.7%.

Case number calculation

The sample size was calculated on the basis of a one-sided t-test with paired samples, for which the following values and assumptions apply:

MCID: ∆ = 0.8 SD: σ = 2.5 Effect size: d = 0.32 Type I error: α = 0.01 (confidence level 0.99) Type II error: β = 0.2 (power P = 0.80) Type of test: one-sided t-test with paired samples. Expected dropout rate = 20%

Therefore, a sample size of 126 patients is required.

Missing values for primary endpoints in some included subjects due to subject withdrawal, missed visits, or protocol deviations will result in a lower number of patients and may thus compromise the efficiency of the study. An overall rate of ~20% is expected.

Primary study objective Improvement in HbA1c value by an average of at least 0.8%

Secondary study objectives

• Investigation of the frequency of adverse side effects (dislocation, need for premature removal of the implant)
• Determination of the rate of successfully treated patients (HbA1c reduction of at least 0.8%)
• Improvement in liver elasticity (elastography)
• Weight loss (excess weight loss (EWL))