Clinical trial NCT01521312: ACute and Chronic Effects of Saxagliptin
Official title: A Randomized, Double Blind, Placebo Controlled, Pilot Study to Evaluate ACute and Chronic Effects of Saxagliptin on Impaired Glucose Tolerance and micro-and Macro-vascular Integrators
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Impaired Glucose Tolerance
Keywords: Impaired glucose tolerance
Saxagliptin
Cardiovascular risk integrators
Vago-sympathetic activity
Arterial stiffness
Endothelial function
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2012-01-30
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Glucose ACCES study will explore the acute and long term (12-week treatment) effects of saxagliptin in patients with impaired glucose tolerance during fasting and after a standardised breakfast. The investigations will be performed on:

* glycemic parameters
* on cardiovascular parameters

Detailed description: The aim of this pilot study is to compare in patients with impaired glucose tolerance the effects of saxagliptin versus placebo:

(i) on glucose metabolism (ii) on vago-sympathetic activity, arterial stiffness and endothelial function. A total of 36 patients will be recruited in the department of Endocrinology-Diabetology-Nutrition of Jean VERDIER hospital, AP-HP, Bondy, France.

The measurements will be performed in the morning 1) at the time of randomisation (Acute ACCES study) and 2) 11-14 weeks after the beginning of saxagliptin or placebo (Chronic ACCES study).

We will evaluate at fasting and each hour after a standardized breakfast:

(i) biological and metabolic parameters. Furthermore, an oral glucose tolerance test will be performed at the end of the study.

(ii) by non-invasive devices arterial stiffness (Sphygmocor®), endothelial function (ENDOPAT 2000® ), cutaneous microcirculation (laser doppler Perimed ®.PF 5010) and cardiac autonomic function(task force monitor®).

Eligibility criteria: Inclusion Criteria:

* Social security affiliation
* Persons without TUTORSHIP that can freely agree to participate to the study
* Age between 18 to 70 years
* Impaired glucose tolerance diagnosed during the previous month.

Exclusion criteria:

* Pregnancy
* Breast feeding
* Diabetes
* No contraception
* Body Mass Index \> 45 kg/m²
* Arterial blood pressure \> 160/110 mmHg
* Creatinine clearance \< 60 ml/min
* Severe hepatocellular insufficiency
* Chronic respiratory disease
* Anaemia (Hemoglobin \< 10 g/dl)
* Peripheral arterial occlusive disease
* Heart failure
* Cardiac arrhythmia

Primary outcomes:
measure: Vago-sympathetic activity.
timeFrame: First day (inclusion) and after 11-14 weeks of treatment
measure: arterial stiffness
timeFrame: First day (inclusion) and after 11-14 weeks of treatment
measure: endothelial function
timeFrame: First day (inclusion) and after 11-14 weeks of treatment
measure: oral glucose tolerance test.
timeFrame: First day (inclusion) and after 11-14 weeks of treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Bondy
country: France
facility: Jean Verdier hospital, Department of Endocrinology-Diabetology-Nutrition
Study officials:
affiliation: Jean Verdier Hospital - Department of Endocrinology-Diabetology-Nutrition
name: Paul Valensi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rezki A, Cosson E, Fysekidis M, Chiheb S, Vicaut E, Valensi P. Acute and long-term effects of saxagliptin on a set of cardiovascular targets measured at fasting and post-prandially in obese patients with impaired glucose tolerance: A placebo-controlled study. Nutr Metab Cardiovasc Dis. 2021 Sep 22;31(10):2945-2958. doi: 10.1016/j.numecd.2021.06.017. Epub 2021 Jul 1.
citation: Rezki A, Fysekidis M, Chiheb S, Vicaut E, Cosson E, Valensi P. Acute and long-term effects of saxagliptin on post-prandial glycemic response in obese patients with impaired glucose tolerance. Nutr Metab Cardiovasc Dis. 2021 Apr 9;31(4):1257-1266. doi: 10.1016/j.numecd.2020.12.025. Epub 2020 Dec 31.