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

Toulouse University Hospital

Status and phase

Completed

Phase 2

Conditions

Diabetes Mellitus

Treatments

Drug: Vildagliptin

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01452113

1004003

Details and patient eligibility

About

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.

Full 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.

Enrollment

21 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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