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 [email protected] 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

• Bamberg Social Foundation - Bamberg Clinic
• Charité Berlin
• University Hospital Bochum
• Dresden Municipal Hospital
• St. Georg Hospital, Leipzig
• University Hospital Leipzig
• University Hospital Mannheim
• 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 [email protected] 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))

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 order 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.