Neuropeptide Y and Sympathovagal Balance (NPY)

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

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).

Study Overview

• Status: Completed
• Conditions: Physical Activity; Sympathetic Nervous System; Secretion; Catecholamine
• Intervention / Treatment: Drug: Placebo oral capsule; Other: ergometric test in healthy volunteers; Drug: Saxagliptin 5mg

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 Type: Interventional
• Enrollment (Actual): 7
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Vaud
    • Lausanne, Vaud, Switzerland, 1011
      • Service de néphrologie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 24 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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
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	Other: ergometric test in healthy volunteers; The volunteers will undergo an ergometric test in each session; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Eric Grouzmann
• Collaborators: grégoire millet; grégoire wuerzner; Nicolas Bourdillon; Philippe Eugster
• Investigators: Principal Investigator: Eric Grouzmann, Dr, Centre Hospitalier Universitaire Vaudois

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2018
• Primary Completion (Actual): July 18, 2018
• Study Completion (Actual): April 15, 2019

Study Registration Dates

• First Submitted: April 19, 2019
• First Submitted That Met QC Criteria: April 29, 2019
• First Posted (Actual): May 1, 2019

Study Record Updates

• Last Update Posted (Actual): May 1, 2019
• Last Update Submitted That Met QC Criteria: April 29, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: neuropeptide Y,catecholamine, exercise
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Saxagliptin
• Other Study ID Numbers: 2018-00569

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: all IPD that underlie results in a publication

Drug and device information, study documents

• 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.: No