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

Sponsors

Lead Sponsor: University Hospital, Toulouse

Collaborator: Institute of Molecular Medicine of Rangueil (I2MR)
Faculty of Medicine, Toulouse
Novartis Pharmaceuticals

Source 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.

Overall Status Completed
Start Date October 2010
Completion Date March 2013
Primary Completion Date January 2013
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
plasma glucagon concentration 120 min post stantardized meal
Secondary Outcome
Measure Time Frame
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
Enrollment 21
Condition
Intervention

Intervention Type: Drug

Intervention Name: Vildagliptin

Description: one 50 mg tablet per os

Other Name: 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

Gender: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Healthy Volunteers: No

Overall Official
Location
Facility: UH Toulouse
Location Countries

France

Verification Date

March 2014

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: neuropathy

Type: Other

Description: patients with autonomic neuropathy

Label: control

Type: Other

Description: patients without autonomic neuropathy (ewing score <= 0.5)

Acronym DPPNAC
Study Design Info

Allocation: Non-Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Basic Science

Masking: None (Open Label)

Source: ClinicalTrials.gov