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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01452113

Acronym

DPPNAC

Enrollment

Registered

2011-10-14

Start date

2010-10-31

Completion date

2013-03-31

Last updated

2014-03-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes Mellitus

Keywords

Diabetes Mellitus, DPP-IV protein, Glucagon-Like Peptide 1, autonomic neuropathy

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.

Interventions

DRUGVildagliptin

one 50 mg tablet per os

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

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

Design outcomes

Primary

Measure	Time frame
plasma glucagon concentration	120 min post stantardized meal

Secondary

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

Countries

France

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026