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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Drug: Vildagliptin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: neuropathy<br>patients with autonomic neuropathy | Drug: Vildagliptin<br>* one 50 mg tablet per os<br>* Other names: GALVUS;|
| Other: control<br>patients without autonomic neuropathy (ewing score <= 0.5) | Drug: Vildagliptin<br>* one 50 mg tablet per os<br>* Other names: GALVUS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma glucagon concentration |  | 120 min post stantardized meal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, DPP-IV protein, Glucagon-Like Peptide 1, autonomic neuropathy