Neuropeptide Y and Sympathovagal Balance (NPY)

Eric Grouzmann

Status and phase: Completed; Early Phase 1

Conditions: Secretion; Catecholamine; Sympathetic Nervous System; Physical Activity

Treatments: Drug: Saxagliptin 5mg; Other: ergometric test in healthy volunteers; Drug: Placebo oral capsule

Study type: Interventional

Funder types: Other

Identifiers

NCT03933787

2018-00569

Details and patient eligibility

About

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).

Full 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.

Enrollment: 7 patients

Sex: Male

Ages: 24 to 30 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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7 participants in 2 patient groups, including a placebo group

mannitol in a tablet

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo oral capsule

Other: ergometric test in healthy volunteers

Saxagliptin in a tablet

Active Comparator group

Description:

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

Treatment:

Other: ergometric test in healthy volunteers

Drug: Saxagliptin 5mg