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

This study has been completed.
Sponsor:
Collaborators:
Institute of Molecular Medicine of Rangueil (I2MR)
Faculty of Medicine, Toulouse
Novartis Pharmaceuticals
Information provided by (Responsible Party):
University Hospital, Toulouse
ClinicalTrials.gov Identifier:
NCT01452113
First received: February 9, 2011
Last updated: March 11, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus
Drug: Vildagliptin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University Hospital, Toulouse:

Primary Outcome Measures:
  • plasma glucagon concentration [ Time Frame: 120 min post stantardized meal ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • GLP-1 [ Time Frame: T-30, 0, 15, 30, 60, 90, 120, 180 min post standardized meal ] [ Designated as safety issue: No ]
  • GIP [ Time Frame: T-30,0, 15, 30, 60, 90, 120, 180 min post standardized meal ] [ Designated as safety issue: No ]

Enrollment: 21
Study Start Date: October 2010
Study Completion Date: March 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
neuropathy
patients with autonomic neuropathy
Drug: Vildagliptin
one 50 mg tablet per os
Other Name: GALVUS
control
patients without autonomic neuropathy (ewing score <= 0.5)
Drug: Vildagliptin
one 50 mg tablet per os
Other Name: GALVUS

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01452113

Locations
France
UH Toulouse
Toulouse, France, 31059
Sponsors and Collaborators
University Hospital, Toulouse
Institute of Molecular Medicine of Rangueil (I2MR)
Faculty of Medicine, Toulouse
Novartis Pharmaceuticals
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
  More Information

No publications provided

Responsible Party: University Hospital, Toulouse
ClinicalTrials.gov Identifier: NCT01452113     History of Changes
Other Study ID Numbers: 1004003
Study First Received: February 9, 2011
Last Updated: March 11, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Toulouse:
Diabetes Mellitus
DPP-IV protein
Glucagon-Like Peptide 1
autonomic neuropathy

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Nervous System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Vildagliptin
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014