Neuropeptide Y and Sympathovagal Balance
Clinicaltrials.gov identifier recruitment status First Posted Last update posted
NCT03933787 Completed May 1, 2019 May 1, 2019

study description
Brief Summary

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).

Condition or Disease: Physical Activity
Sympathetic Nervous System
Secretion; Catecholamine
Intervention/treatment: Drug: Saxagliptin 5mg
Drug: Placebo oral capsule
Other: ergometric test in healthy volunteers
Phase: Early Phase 1
Detailed Description

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.


study design
Study Type: Interventional
Estimated Enrollment : 7 participants
Intervention Model : Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Neuropeptide Y Function in the Sympathovagal Balance During an Ergometric Test in Healthy Volunteers
Actual Study Start Date: June 2018
Actual Primary Completion Date: July 2018
Actual Study Completion Date: April 2019

Arms and interventions
Arm Intervention/treatment
Active Comparator: Saxagliptin in a tablet
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
Randomised study: session 1 the volunteer will receive either saxagliptin or placebo. Session 2 the volunteer will receive the placebo or saxagliptin

Other: ergometric test in healthy volunteers
The volunteers will undergo an ergometric test in each session
Placebo Comparator: mannitol in a tablet
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
Randomised study: session 1 the volunteer will receive either saxagliptin or placebo. Session 2 the volunteer will receive the placebo or saxagliptin

Other: ergometric test in healthy volunteers
The volunteers will undergo an ergometric test in each session
outcome measures
Primary Outcome Measures: 1. Heart rate change variability assessed at the end of each exercise [ Time Frame: 5 hours and 30 minutes ]
RMSSD (Root mean square of successive RR interval differences) measurement
2. Heart rate change variability assessed at the end of each exercise [ Time Frame: 5 hours and 30 minutes ]
normalized low frequency (nLF) measurement
Secondary Outcome Measures: 1. NPY 1-36 secretion [ Time Frame: 5 hours and 30 minutes ]
Peak Plasma Concentration [Cmax]
2. NPY 3-36 secretion [ Time Frame: 5 hours and 30 minutes ]
Half-life [t1/2]
3. NPY3-36 secretion [ Time Frame: 5 hours and 30 minutes ]
Area under the plasma concentration versus time curve [AUC]
4. NPY3-36 secretion [ Time Frame: 5 hours and 30 minutes ]
Peak Plasma Concentration [Cmax]
5. Catecholamine secretion [ Time Frame: 5 hours and 30 minutes ]
Half-life [t1/2]
6. Catecholamine secretion [ Time Frame: 5 hours and 30 minutes ]
Area under the plasma concentration versus time curve [AUC]
7. Catecholamine secretion [ Time Frame: 5 hours and 30 minutes ]
Peak Plasma Concentration [Cmax]
8. NPY 1-36 secretion [ Time Frame: 5 hours and 30 minutes ]
half-life [t1/2]
9. NPY 1-36 secretion [ Time Frame: 5 hours and 30 minutes ]
Area under the plasma concentration versus time curve [AUC]

Eligibility Criteria
Ages Eligible for Study: 24 to 30 Years (Adult)
Sexes Eligible for Study: Male
Accepts Healthy Volunteers: Yes
Criteria

Inclusion Criteria:

1. Healthy male subjects aged between 18 and 30 years.

2. Non smoking

3. Practicing at least 3 hours physical activity per week

4. Absence of significant findings in the medical history and physical examination as judged by the Investigator, especially for cardiovascular, pulmonary, haematological and nervous systems

5. Ability to understand the procedures, agreement to participate and willingness to give written informed consent

6. Co-operative attitude and availability for scheduled visits over the entire study period.

Exclusion Criteria:

1. 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.

2. History of major cardiovascular, pulmonary, hepatic, immunological, renal, haematological, gastrointestinal, genitourinary, neurological, or rheumatologic disorders

3. rhinosinusitis

4. Urinary tract infection

5. Hypertension defined as supine blood pressure >150/90 mmHg or recurrent hypotensive events considered as clinically relevant or documented orthostatic hypotension


Contacts and Locations
Contacts
Locations
Switzerland, Vaud Service de Néphrologie Lausanne
Sponsors and Collaborators
Eric Grouzmann
grégoire wuerzner
grégoire millet
Nicolas Bourdillon
Philippe Eugster
Investigator
Principal Investigator : Eric Grouzmann, Dr Centre Hospitalier Universitaire Vaudois
More Information
Responsible Party : Eric Grouzmann
ClinicalTrials.gov Identifier : NCT03933787     
Other Study ID Numbers : 2018-00569
First Posted : May 1, 2019
Last Update Posted : May 1, 2019
Last Verified : April 2019
Individual Participant
Data (IPD) Sharing
Statement:
 
Plan to Share IPD: Undecided
Plan Description: all IPD that underlie results in a publication
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Eric Grouzmann: neuropeptide Y,catecholamine, exercise