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

Phase 2

Completed

• Conditions: Diabetes Mellitus
• Interventions: Drug: Vildagliptin

• Registration Number: NCT01452113
• Lead Sponsor: University Hospital, Toulouse

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.

Study Timeline

• Study Start: 2010-10
• Study First Submitted: 2011-02-09
• Study First Submitted QC: 2011-10-13
• Study First Posted: 2011-10-14
• Primary Completion: 2013-01
• Study Completion: 2013-03
• Status Verified: 2014-03
• Last Update Submitted: 2014-03-11
• Last Update Posted: 2014-03-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
control	Vildagliptin	patients without autonomic neuropathy (ewing score \<= 0.5)
neuropathy	Vildagliptin	patients with autonomic neuropathy

Primary Outcome Measures

Name	Time	Method
plasma glucagon concentration	120 min post stantardized meal

Secondary Outcome Measures

Name	Time	Method
GLP-1	T-30, 0, 15, 30, 60, 90, 120, 180 min post standardized meal
GIP	T-30,0, 15, 30, 60, 90, 120, 180 min post standardized meal

Trial Locations

Locations (1)

UH Toulouse; 🇫🇷 Toulouse, France