Metabolic Effects of Duodenal Jejunal Bypass Liner for Type 2 Diabetes Mellitus (DJBL-T2DM)

June 10, 2016 updated by: Diethelm Tschoepe, Ruhr University of Bochum

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Observational

Enrollment (Actual)

19

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Bad Oeynhausen, Germany, 32545
        • Herz- und Diabeteszentrum

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Retrospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
DJBL implant-group

T2DM Patients implanted with a DJBL (Duodenal jejunal Bypass liner, EndoBarrier, GI Dynamics) due to medical reasons.

The subjects were regular in-patients of the Diabetes Center at the Heart and Diabetes Center NRW, Germany and gave informed consent for related procedures and data handling. The subjects had BMI ≥35 kg/m2, T2DM, and a history of frustrated weight loss attempts. Exclusion criteria: history of gastric surgery, gastric or duodenal ulcers, thyroid disorders, gastrointestinal disorders with intestinal resorption dysfunction, therapy with oral anticoagulants, use of acetyl salicylic acid or non-steroidal anti-inflammatory drugs, drug abuse (incl. alcohol), symptomatic cardiovascular disease, renal insufficiency (GFR <50 ml/min), pregnancy or breast feeding.
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
Other Names:
  • EndoBarrier

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
weight loss in kg
Time Frame: 12 months
weight loss defined as excess weight loss
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in body fat in %, measured via bioimpedance scaling
Time Frame: 12 months
effect of DJBL on body composition in overweight T2DM patients determined by bioimpedance scaling
12 months
Change in HbA1c in mmol/mol
Time Frame: 12 months
effect of DJBL on metabolic regulation in overweight T2DM patients
12 months
Change in LDL-cholesterol in mg/dl
Time Frame: 12 months
effect of DJBL on metabolic regulation in overweight T2DM patients
12 months
Change in triglycerides in mg/dl
Time Frame: 12 months
effect of DJBL on metabolic regulation in overweight T2DM patients
12 months
Change in liver enzyme aspartate aminotransferase (ASAT) in U/l
Time Frame: 12 months
effect of DJBL on metabolic regulation in overweight T2DM patients
12 months
Change in liver enzyme alanine aminotransferase (ALAT) in U/l
Time Frame: 12 months
effect of DJBL on metabolic regulation in overweight T2DM patients
12 months
changes in intestinal enzyme levels (GLP-1) in pmol/l/120 min during mixed meal tolerance test
Time Frame: 12 months
effect of DJBL and intestine/pancreatic axis for metabolic control
12 months
changes in intestinal enzyme levels (GIP) in ng/ml/120 min during mixed meal tolerance test
Time Frame: 12 months
effect of DJBL and intestine/pancreatic axis for metabolic control
12 months
changes in Ghrelin in ng/ml/120 min during mixed meal tolerance test
Time Frame: 12 months
effect of DJBL and intestine/pancreatic axis for metabolic control
12 months
changes in Leptin in ng/ml/120 min during mixed meal tolerance test
Time Frame: 12 months
effect of DJBL and intestine/pancreatic axis for metabolic control
12 months
changes in pancreatic enzyme levels (Insulin) in U/l/120 min during mixed meal tolerance test
Time Frame: 12 months
effect of DJBL and intestine/pancreatic axis for metabolic control
12 months
changes in pancreatic enzyme levels (Proinsulin) in nmol/l/120 min during mixed meal tolerance test
Time Frame: 12 months
effect of DJBL and intestine/pancreatic axis for metabolic control
12 months
effect on blood pressure measured in mmHg
Time Frame: 12 months
follow up by regular vital signs,
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ruhr University of Bochum

Investigators

  • Principal Investigator: Diethelm Tschoepe, Prof MD, Herz Und Diabeteszentrum NRW

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2011

Primary Completion (Actual)

June 1, 2015

Study Completion (Actual)

June 1, 2015

Study Registration Dates

First Submitted

May 25, 2016

First Submitted That Met QC Criteria

June 10, 2016

First Posted (Estimate)

June 15, 2016

Study Record Updates

Last Update Posted (Estimate)

June 15, 2016

Last Update Submitted That Met QC Criteria

June 10, 2016

Last Verified

June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DJBL-HDZ

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

after publication of results

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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