Effect of Autonomic Neuropathy on the Efficacy of a DPP-IV Inhibitor (Galvus) Therapy (DPPNAC)

March 11, 2014 updated by: University Hospital, Toulouse

Effect of a DPP-IV Inhibitor Treatment on the Secretion of Glucagon in Patients Presenting With Type 1 Diabetes Mellitus With or Without Autonomic Neuropathy

The purpose of this study is to compare the effect of a single administration of a DPP-IV inhibitor (vildagliptin: Galvus ®) versus no treatment over two populations of diabetic patients: without diabetic autonomic neuropathy (NA, i.e. the control group) and with diabetic autonomic neuropathy (i.e. the neuropathy group). The investigators hypothesize that the therapeutic efficacy of DPP-IV inhibitors is partly mediated by the autonomic nervous system. This hypothesis will be validated if a lower glycemic response to DPP-IV inhibitor treatment is observed for the neuropathy group compared to control.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Recently published work has demonstrated in animals that the control of pancreatic hormone secretion is due, at least in part, to the action of GLP-1 on the via the autonomic nervous system. Therefore, rhe investigators hypothesized that altered autonomic nervous system could explain, at least in part, the altered therapeutic efficacy of DPP-IV inhibitors observed in some patients. Our aim is to validate this concept in humans.

The objective of this physiopathological, monocentric, comparative, open, parallel study is to compare the effect of a single administration of a DPP-IV (vildagliptin: Galvus ®) over two populations of type 1 diabetic patients: a control group of 12 patients without diabetic autonomic neuropathy (NA) and a group of 12 patients with NA.

This proof of concept study will enrol type 1 diabetic patients to avoid confounding factors related to endogen insulin secretion and frequent polymedication of type 2 diabetic patients. The response will be evaluated for each patient by the relative difference between pre-and post-glucagon concentrations following a test meal, measured in the absence and presence of treatment with DPP4 inhibitor. Expected results: the DPP-4 inhibitor should lead to a reduction of about 20 to 30% of the glucagon level in patients without NA and a smaller or no decrease in patients with NA.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 2

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

  • France
      • Toulouse, France, 31059
        • Uh Toulouse

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

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • type 1 diabetes mellitus
  • multiple daily insulin injections therapy or continuous insulin infusion (insulin pomp) therapy
  • recent (<1 year) written diagnosis of autonomic neuropathy available
  • ewing score > 2 for patients to be included in the "neuropathy" group
  • ewing score <= 0.5 for patients to be included in the '"control" group
  • HbA1C <= 10% at the screening visit and stable (+/- 1%)between the autonomous neuropathy diagnosis and the inclusion visit

Exclusion Criteria:

  • severe chronic renal insufficiency defined by an estimated GFR<30 ml/min calculated by MDRD formula)
  • proliferative retinopathy needing panphotocoagulation
  • hepatic enzymes (ALAT, ASAT) greater than 3 times the upper limit
  • congestive heart failure of NYHA functional class III-IV
  • clinical signs of gastroparesis
  • ongoing gastric emptying therapy
  • history of bariatric surgery
  • galvus therapy contra indications: known allergy or hypersensitivity of princeps or excipients, galactose intolerance, lapp lactase deficiency, glucose - galactose malabsorption
  • ongoing systemic corticoids therapy
  • metformin therapy during the day before each study visit
  • haemoglobin alteration
  • pregnancy or pregnancy willing
  • lactation
  • ongoing clinical study participation

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

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: neuropathy
patients with autonomic neuropathy
Drug: Vildagliptin
one 50 mg tablet per os
Other Names:
  • GALVUS
OTHER: control
patients without autonomic neuropathy (ewing score <= 0.5)
Drug: Vildagliptin
one 50 mg tablet per os
Other Names:
  • GALVUS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
plasma glucagon concentration
Time Frame: 120 min post stantardized meal
120 min post stantardized meal

Secondary Outcome Measures

Outcome Measure
Time Frame
GLP-1
Time Frame: T-30, 0, 15, 30, 60, 90, 120, 180 min post standardized meal
T-30, 0, 15, 30, 60, 90, 120, 180 min post standardized meal
GIP
Time Frame: T-30,0, 15, 30, 60, 90, 120, 180 min post standardized meal
T-30,0, 15, 30, 60, 90, 120, 180 min post standardized meal

Collaborators and Investigators

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

Sponsor

University Hospital, Toulouse

Collaborators

Novartis Pharmaceuticals
Institute of Molecular Medicine of Rangueil (I2MR)
Faculty of Medicine, Toulouse

Investigators

  • Study Director: Remy Burcelin, PHD, Institut National de la Santé Et de la Recherche Médicale, France
  • Principal Investigator: Hélène Hanaire, MD PHD, Uh Toulouse

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, 2010

Primary Completion (ACTUAL)

January 1, 2013

Study Completion (ACTUAL)

March 1, 2013

Study Registration Dates

First Submitted

February 9, 2011

First Submitted That Met QC Criteria

October 13, 2011

First Posted (ESTIMATE)

October 14, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

March 12, 2014

Last Update Submitted That Met QC Criteria

March 11, 2014

Last Verified

March 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1004003

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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