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

February 9, 2011
March 11, 2014
October 2010
January 2013   (final data collection date for primary outcome measure)
plasma glucagon concentration [ Time Frame: 120 min post stantardized meal ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01452113 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Effect of Autonomic Neuropathy on the Efficacy of a DPP-IV Inhibitor (Galvus) Therapy
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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Diabetes Mellitus
Drug: Vildagliptin
one 50 mg tablet per os
Other Name: GALVUS
  • neuropathy
    patients with autonomic neuropathy
    Intervention: Drug: Vildagliptin
  • control
    patients without autonomic neuropathy (ewing score <= 0.5)
    Intervention: Drug: Vildagliptin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
21
March 2013
January 2013   (final data collection date for primary outcome measure)

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
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT01452113
1004003
Yes
University Hospital, Toulouse
University Hospital, Toulouse
  • Institute of Molecular Medicine of Rangueil (I2MR)
  • Faculty of Medicine, Toulouse
  • Novartis Pharmaceuticals
Study Director: Remy Burcelin, PHD Institut National de la Santé Et de la Recherche Médicale, France
Principal Investigator: Hélène Hanaire, MD PHD UH Toulouse
University Hospital, Toulouse
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP