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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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Nervous System Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Vildagliptin
Dipeptidyl-Peptidase IV Inhibitors
Enzyme Inhibitors
Hypoglycemic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors

ClinicalTrials.gov processed this record on November 27, 2014