Metabolic Effects of Duodenal Jejunal Bypass Liner for Type 2 Diabetes Mellitus

Obesity Clinical Trial

— DJBL-T2DM  

Official title:

Metabolic Effects of Duodenal Jejunal Bypass Liner for the Treatment of Adipose Patients With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02800668
• Other study ID #: DJBL-HDZ
• Status: Completed
• Phase: N/A
• First received: May 25, 2016
• Last updated: June 10, 2016
• Start date: October 2011
• Est. completion date: June 2015

Study information

• Verified date: June 2016
• Source: Ruhr University of Bochum
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Observational

Clinical Trial Summary

Implantation of a duodenal-jejunal endoluminal bypass liner (DJBL) has shown to induce weight loss and to improve metabolic parameters. DJBL is a reversible endoduodenal sleeve mimicking biliodigestive digestion while lacking risks and limitations of bariatric surgery.

Effects on metabolic control, body mass parameters, appetite regulation, glucose tolerance, organ health, and lipid profile were determined in 16 morbidly overweight patients with type 2 diabetes mellitus. In addition, relevant hormones (Leptin, ghrelin, gastric inhibitory peptide, glucagon-like peptide 1, and insulin) were measured by enzyme-linked immunosorbent assay (ELISA) and chemiluminescent microparticle immunoassay (CMIA) at 0, 1 and 32, and 52 weeks post-implant following a mixed meal tolerance test, which was applied for diagnostic purposes only.

Description:

A total of 18 subjects (4 women and 14 men) aged 39 to 66 years underwent implantation of the DJBL.The subjects were regular patients of the Diabetes Center at the Herz- und Diabeteszentrum Nordrhein-Westfalen (HDZ NRW), Germany and gave informed consent for related procedures and data handling. The subjects had body mass index (BMI) ≥35 kg/m2, type 2 diabetes mellitus (T2DM), and a history of frustrated weight loss attempts. Exclusion criteria were: history of gastric surgery, gastric or duodenal ulcers, thyroid disorders, gastrointestinal disorders associated with intestinal resorption dysfunction, therapy with oral anticoagulants like marcumar, use of acetyl salicylic acid or non-steroidal anti-inflammatory drugs, drug abuse (incl. alcohol), symptomatic cardiovascular disease including heart failure New York Heart Association (NYHA) IV, renal insufficiency defined as glomerular filtration rate (GFR) <50 ml/min, pregnancy or breast feeding.

Study design All patients received the DJBL due to medical reasons, not for study purposes. All patients underwent pre-implantation and follow-up examinations (1 week, 32 weeks and 52 (explantation) weeks after implantation). Every examination included a thorough body examination, electrocardiogram (ECG), and the body composition measurement by bio-impedance scaling (type: BC418MA, Tanita, Amsterdam, the Netherlands). Upon implantation, antidiabetic medication was adapted, patients were followed up to adjust antidiabetic regimen. Dietary advice was given to the patients by a professional dietician upon implantation procedure, and liquid diet was started the day before implantation and continued for two additional days followed by puréed diet for four days. Patients decided to turn back to normal diet upon tolerance; fibre rich dietary components were prohibited during the treatment period. Treatment with glucagon-like peptide-1 (GLP-1) or dipeptidyl-peptidase-4 (DPP4) based medication (Exenatide, Liraglutide, Lixisenatide or Sitagliptin, Vildagliptin) was initiated in cases that fasting C-peptide levels were >750 pmol/l. Insulin dosage was reduced after implantation to avoid risk of hypoglycaemia. Sulfonylurea treatment was stopped after implantation.

Mixed meal tolerance tests Mixed meal tolerance tests (MMTT) were performed in fasting state as routine diagnostic tool to assess metabolism parameters and gut hormones described below. In the course of a MMTT every patient consumed a highly caloric drink (Fortimel regular 2 093 Kilojoules (KJ), Nutricia GmbH, Erlangen, Germany) containing carbohydrates (41 energy(EN)%), proteins (40 EN%) and fats (19 EN%), simulating an average meal. Blood samples were taken at fixed intervals: before drinking, after 10, 30, 60, 90, 120 min. DPP4 inhibitor was added to prevent autodigestion of GLP-1 immediately after sampling, Hydroxymercuribenzoic acid was added to plasma per protocol to prevent ghrelin digestion. Samples were stored after centrifugation at -80°C until assayed for the gut hormones ghrelin, GLP-1, gastric inhibitory peptide, leptin as well as the metabolism parameters glucose, insulin, C-peptide, and proinsulin.

Biochemical assessment Laboratory assessments were done in fasting state. Venipuncture was performed the morning after overnight fasting one day before the planned procedure, one week, 8, and 12 months after implantation. Blood samples were processed for subsequent analysis within 20 min of venipuncture. Serum concentrations were measured by commercial available kits of total ghrelin (ELISA, Merck Chemicals Gesellschaft mit beschränkter Haftung (GmbH), Schwalbach, Germany), leptin (ELISA, DRG-International, Inc., USA), active GLP-1 (ELISA, epitope Diagnostics, San Diego, USA), gastric inhibitory Peptide (GIP) (ELISA, DRG-International, Inc., USA), Insulin (CMIA, Abbott, Wiesbaden, Germany), C-peptide (CMIA, Abbott, Wiesbaden, Germany), Proinsulin (ELISA, TecoMedical Bunde, Germany) and glucose (CMIA, Abbott, Wiesbaden Germany).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• T2DM

• body mass index (BMI) =35 kg/m2

• history of frustrated weight loss attempts

Exclusion Criteria:

• history of gastric surgery, gastric or duodenal ulcers

• thyroid disorders

• gastrointestinal disorders associated with intestinal resorption dysfunction

• therapy with oral anticoagulants like marcumar

• use of acetyl salicylic acid or non-steroidal anti-inflammatory drugs

• drug abuse (incl. alcohol)

• symptomatic cardiovascular disease including heart failure New York Heart Association IV

• renal insufficiency defined as GFR <50 ml/min

• pregnancy or breast feeding

Study Design

Observational Model: Case-Only, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Obesity
• Type 2 Diabetes Mellitus

Intervention

Device:
• DJBL (Duodenal jejunal bypass liner, EndoBarrier)
Implantation of EndoBarrier after medical and patient's decision, Duration of treatment 12 months in maximum, follow up for 4 weeks after Explantation, follow up during treatment by physical examination, ECG control, sampling and analysis of blood parameters, mixed meal tolerance tests only for diagnostic purposes to assess gut hormonal changes and metabolic parameters

Locations

Country	Name	City	State
Germany	Herz- und Diabeteszentrum	Bad Oeynhausen

Sponsors (1)

Lead Sponsor	Collaborator
Ruhr University of Bochum

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	weight loss in kg	weight loss defined as excess weight loss	12 months	No
Secondary	Change in body fat in %, measured via bioimpedance scaling	effect of DJBL on body composition in overweight T2DM patients determined by bioimpedance scaling	12 months	No
Secondary	Change in HbA1c in mmol/mol	effect of DJBL on metabolic regulation in overweight T2DM patients	12 months	Yes
Secondary	Change in LDL-cholesterol in mg/dl	effect of DJBL on metabolic regulation in overweight T2DM patients	12 months	No
Secondary	Change in triglycerides in mg/dl	effect of DJBL on metabolic regulation in overweight T2DM patients	12 months	No
Secondary	Change in liver enzyme aspartate aminotransferase (ASAT) in U/l	effect of DJBL on metabolic regulation in overweight T2DM patients	12 months	No
Secondary	Change in liver enzyme alanine aminotransferase (ALAT) in U/l	effect of DJBL on metabolic regulation in overweight T2DM patients	12 months	No
Secondary	changes in intestinal enzyme levels (GLP-1) in pmol/l/120 min during mixed meal tolerance test	effect of DJBL and intestine/pancreatic axis for metabolic control	12 months	No
Secondary	changes in intestinal enzyme levels (GIP) in ng/ml/120 min during mixed meal tolerance test	effect of DJBL and intestine/pancreatic axis for metabolic control	12 months	No
Secondary	changes in Ghrelin in ng/ml/120 min during mixed meal tolerance test	effect of DJBL and intestine/pancreatic axis for metabolic control	12 months	No
Secondary	changes in Leptin in ng/ml/120 min during mixed meal tolerance test	effect of DJBL and intestine/pancreatic axis for metabolic control	12 months	No
Secondary	changes in pancreatic enzyme levels (Insulin) in U/l/120 min during mixed meal tolerance test	effect of DJBL and intestine/pancreatic axis for metabolic control	12 months	No
Secondary	changes in pancreatic enzyme levels (Proinsulin) in nmol/l/120 min during mixed meal tolerance test	effect of DJBL and intestine/pancreatic axis for metabolic control	12 months	No
Secondary	effect on blood pressure measured in mmHg	follow up by regular vital signs,	12 months	No