Neuropeptide Y and Sympathovagal Balance

Study Overview
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Brief Summary
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Neuropeptide Y (NPY) activates the sympathetic and vagal nervous systems through the Y1 and Y2 receptors. This double-blind placebo-controlled crossover study investigated the sympathovagal balance during three exercises on a cycloergometer in healthy volunteers treated with saxagliptin (DPP4 inhibitor).

Detailed Description
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Pharmacological studies indicate that NPY has a role as a co-transmitter associated with catecholamines to maintain cardiovascular homeostasis. The development of a selective and sensitive assay of NPY1-36 (vasoconstrictor) and NPY3-36 (vasodilator) by LC-MS/MS will confirm this modulating role of NPY in sympatho vagal balance in healthy young subjects. This project should lead to a better understanding of the contribution of NPY to exercise physiology through a double-blind randomized study using a DPP4 inhibitor (Saxagliptin) used for the treatment of type 2 diabetes, blocking the formation of NPY3-36 and thus enhancing the effect of NPY1-36. The interest of this study will be to find targets other than adrenergic receptors in the regulation of sympathetic and parasympathetic systems during exercise.

Official Title
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Neuropeptide Y Function in the Sympathovagal Balance During an Ergometric Test in Healthy Volunteers

Conditions
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Physical Activity, Sympathetic Nervous System, Secretion; Catecholamine

Intervention / Treatment
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* Drug: Saxagliptin 5mg
* Drug: Placebo oral capsule
* Other: ergometric test in healthy volunteers


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects aged between 18 and 30 years. Non smoking Practicing at least 3 hours physical activity per week Absence of significant findings in the medical history and physical examination as judged by the Investigator, especially for cardiovascular, pulmonary, haematological and nervous systems Ability to understand the procedures, agreement to participate and willingness to give written informed consent Co-operative attitude and availability for scheduled visits over the entire study period. Exclusion Criteria: Use of any medication the week prior to study. Paracetamol is permissible before and during study as a concomitant medication but only with Investigator's permission. History of major cardiovascular, pulmonary, hepatic, immunological, renal, haematological, gastrointestinal, genitourinary, neurological, or rheumatologic disorders rhinosinusitis Urinary tract infection Hypertension defined as supine blood pressure >150/90 mmHg or recurrent hypotensive events considered as clinically relevant or documented orthostatic hypotension

Ages Eligible for Study
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Minimum Age: 24 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: double-blind placebo-controlled crossover study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: mannitol in a tablet<br>two tablets containing mannitol in a blister: one tablet provided to each volunteer in a blister 16 hours before the trial and one tablet provided two hours before the clinical trial | Drug: Placebo oral capsule<br>* Randomised study: session 1 the volunteer will receive either saxagliptin or placebo. Session 2 the volunteer will receive the placebo or saxagliptin<br>Other: ergometric test in healthy volunteers<br>* The volunteers will undergo an ergometric test in each session<br>|
| Active Comparator: Saxagliptin in a tablet<br>two tablets containing each 5 mg of Saxagliptin in a blister: one tablet provided to each volunteer in a blister 16 hours before the trial and one tablet provided two hours before the clinical trial | Drug: Saxagliptin 5mg<br>* Randomised study: session 1 the volunteer will receive either saxagliptin or placebo. Session 2 the volunteer will receive the placebo or saxagliptin<br>Other: ergometric test in healthy volunteers<br>* The volunteers will undergo an ergometric test in each session<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate change variability assessed at the end of each exercise | RMSSD (Root mean square of successive RR interval differences) measurement | 5 hours and 30 minutes | 
| Heart rate change variability assessed at the end of each exercise | normalized low frequency (nLF) measurement | 5 hours and 30 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NPY 1-36 secretion | half-life [t1/2] | 5 hours and 30 minutes | 
| NPY 1-36 secretion | Area under the plasma concentration versus time curve [AUC] | 5 hours and 30 minutes | 
| NPY 1-36 secretion | Peak Plasma Concentration [Cmax] | 5 hours and 30 minutes | 
| NPY 3-36 secretion | Half-life [t1/2] | 5 hours and 30 minutes | 
| NPY3-36 secretion | Area under the plasma concentration versus time curve [AUC] | 5 hours and 30 minutes | 
| NPY3-36 secretion | Peak Plasma Concentration [Cmax] | 5 hours and 30 minutes | 
| Catecholamine secretion | Half-life [t1/2] | 5 hours and 30 minutes | 
| Catecholamine secretion | Area under the plasma concentration versus time curve [AUC] | 5 hours and 30 minutes | 
| Catecholamine secretion | Peak Plasma Concentration [Cmax] | 5 hours and 30 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neuropeptide Y,catecholamine, exercise