Clinical trial NCT02800668: Metabolic Effects of Duodenal Jejunal Bypass Liner for Type 2 Diabetes Mellitus
Official title: Metabolic Effects of Duodenal Jejunal Bypass Liner for the Treatment of Adipose Patients With Type 2 Diabetes Mellitus
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Type 2 Diabetes Mellitus
Obesity
Keywords: Duodenal Jejunal Bypass Liner
obesity
weight loss therapy
Lead sponsor: Ruhr University of Bochum
Sponsor class: OTHER
First posted: 2016-06-15
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The subjects were regular inpatients with type 2 Diabetes mellitus of the Diabetes Center at the Heart and Diabetes Center NRW, Germany and gave informed consent for related procedures and data handling

Brief 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.

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: weight loss in kg
timeFrame: 12 months
Secondary outcomes:
measure: Change in body fat in %, measured via bioimpedance scaling
timeFrame: 12 months
measure: Change in HbA1c in mmol/mol
timeFrame: 12 months
measure: Change in LDL-cholesterol in mg/dl
timeFrame: 12 months
measure: Change in triglycerides in mg/dl
timeFrame: 12 months
measure: Change in liver enzyme aspartate aminotransferase (ASAT) in U/l
timeFrame: 12 months
measure: Change in liver enzyme alanine aminotransferase (ALAT) in U/l
timeFrame: 12 months
measure: changes in intestinal enzyme levels (GLP-1) in pmol/l/120 min during mixed meal tolerance test
timeFrame: 12 months
measure: changes in intestinal enzyme levels (GIP) in ng/ml/120 min during mixed meal tolerance test
timeFrame: 12 months
measure: changes in Ghrelin in ng/ml/120 min during mixed meal tolerance test
timeFrame: 12 months
measure: changes in Leptin in ng/ml/120 min during mixed meal tolerance test
timeFrame: 12 months
measure: changes in pancreatic enzyme levels (Insulin) in U/l/120 min during mixed meal tolerance test
timeFrame: 12 months
measure: changes in pancreatic enzyme levels (Proinsulin) in nmol/l/120 min during mixed meal tolerance test
timeFrame: 12 months
measure: effect on blood pressure measured in mmHg
timeFrame: 12 months
Other outcomes:
Locations:
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum
Study officials:
affiliation: Herz und Diabeteszentrum NRW
name: Diethelm Tschoepe, Prof MD
role: PRINCIPAL_INVESTIGATOR
References: