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

NCT ID: NCT01452113

Last Updated: 2014-03-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2013-03-31

Brief Summary

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.

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.

Conditions

Diabetes Mellitus

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

neuropathy

patients with autonomic neuropathy

Group Type: OTHER

Vildagliptin

Intervention Type: DRUG

one 50 mg tablet per os

control

patients without autonomic neuropathy (ewing score \<= 0.5)

Group Type: OTHER

Vildagliptin

Intervention Type: DRUG

one 50 mg tablet per os

Interventions

Vildagliptin

one 50 mg tablet per os

Intervention Type: DRUG

Other Intervention Names

GALVUS

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Molecular Medicine of Rangueil (I2MR)

UNKNOWN

Sponsor Role: collaborator

Faculty of Medicine, Toulouse

UNKNOWN

Sponsor Role: collaborator

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Remy Burcelin, PHD

Role: STUDY_DIRECTOR

Institut National de la Santé Et de la Recherche Médicale, France

Hélène Hanaire, MD PHD

Role: PRINCIPAL_INVESTIGATOR

UH Toulouse

Locations

UH Toulouse

Toulouse, , France

Countries

France

Other Identifiers

1004003

Identifier Type: -

Identifier Source: org_study_id