Neuropeptide Y and Sympathovagal Balance

Early Phase 1

Completed

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

• Registration Number: NCT03933787
• Lead Sponsor: Eric Grouzmann

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).

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 Timeline

• Study Start: 2018-06-05
• Primary Completion: 2018-07-18
• Status Verified: 2019-04
• Study Completion: 2019-04-15
• Study First Submitted: 2019-04-19
• Study First Submitted QC: 2019-04-29
• Last Update Submitted: 2019-04-29
• Study First Posted: 2019-05-01
• Last Update Posted: 2019-05-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 7

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Saxagliptin in a tablet	Saxagliptin 5mg	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
mannitol in a tablet	ergometric test in healthy volunteers	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
Saxagliptin in a tablet	ergometric test in healthy volunteers	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
mannitol in a tablet	Placebo oral capsule	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

Primary Outcome Measures

Name	Time	Method
Heart rate change variability assessed at the end of each exercise	5 hours and 30 minutes	normalized low frequency (nLF) measurement

Secondary Outcome Measures

Name	Time	Method
NPY 1-36 secretion	5 hours and 30 minutes	Peak Plasma Concentration \[Cmax\]
NPY3-36 secretion	5 hours and 30 minutes	Peak Plasma Concentration \[Cmax\]
Catecholamine secretion	5 hours and 30 minutes	Peak Plasma Concentration \[Cmax\]
NPY 3-36 secretion	5 hours and 30 minutes	Half-life \[t1/2\]

Trial Locations

Locations (1)

Service de Néphrologie; 🇨🇭 Lausanne, Vaud, Switzerland