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

Diabetes Mellitus Clinical Trial

— DPPNAC  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01452113
• Other study ID #: 1004003
• Status: Completed
• Phase: Phase 2
• First received: February 9, 2011
• Last updated: March 11, 2014
• Start date: October 2010
• Est. completion date: March 2013

Study information

• Verified date: March 2014
• Source: University Hospital, Toulouse
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: March 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus
• Nervous System Diseases

Intervention

Drug:
• Vildagliptin
one 50 mg tablet per os

Locations

Country	Name	City	State
France	UH Toulouse	Toulouse

Sponsors (4)

Lead Sponsor	Collaborator
University Hospital, Toulouse	Faculty of Medicine, Toulouse, Institute of Molecular Medicine of Rangueil (I2MR), Novartis Pharmaceuticals

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	plasma glucagon concentration		120 min post stantardized meal	No
Secondary	GLP-1		T-30, 0, 15, 30, 60, 90, 120, 180 min post standardized meal	No
Secondary	GIP		T-30,0, 15, 30, 60, 90, 120, 180 min post standardized meal	No