Effects of L-lysine on Adrenal Secretion

Study Overview
=================
Brief Summary
-----------------
Data from the literature and previous in vitro research conducted in the investigators' laboratory (INSERM U413/EA4310, University of Rouen) suggest that adrenal corticosteroid secretion might be controlled by a paracrine mechanism involving serotonin type IV receptor (5-HT 4). L-lysine, a common amino-acid has been shown to act as a 5-HT4 agonist in vitro as well as in vivo. In the present physiology trial, plasma aldosterone and cortisol levels will be measured under treatment with aprepitant versus placebo, in both basal conditions and after activation of the adrenocortical function by various stimuli, including upright posture, metoclopramide, and after a 3 days salt-free diet. All healthy volunteers will be given two substances (L-lysine and placebo) in a random order during two 13 days periods separated by a 14 day-wash-out. This study should allow to determine the role of 5-HT4 receptors in the control of corticosteroid production in normal man.

Detailed Description
-----------------
STUDY DESIGN Proof of concept, interventional, monocentric, randomised, double blind, cross-over study: The effects of L-lysine on corticosteroid secretion will be compared to those of a placebo. STUDY OBJECTIVES Main objective: to verify that adrenal corticosteroid secretion is actually controlled by L-lysine. Secondary objective: to determine the physiological conditions that involve the control of adrenocortical function by t5-HT4 receptors. NUMBER OF SUBJECTS 20 healthy volunteers ELIGIBILITY CRITERIA (see below) DURATION OF STUDY Overall duration: 13 months Inclusion period: 12 months Follow up period (for 1 subject): 5 weeks Exclusion period: 1 month ENDPOINTS PRIMARY ENDPOINT: blood aldosterone variation during orthostatic test SECONDARY ENDPOINTS Basal aldosterone alteration Aldosterone variation during metoclopramide & salt-free diet tests Basal and stimulated (3 different tests) alterations of renin, cortisol & ACTH REGULATORY AUTHORIZATIONS Ethics committee authorization: jan 21,2010 Regulatory authorization: july 9th 2010

Official Title
-----------------
Pilot Study of the Action L-lysine on Aldosterone and Cortisol Secretion in Healthy Volunteers.

Conditions
-----------------
Male, Healthy Volunteers

Intervention / Treatment
-----------------
* Dietary Supplement: L-lysine
* Dietary Supplement: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male subjects; Age ranging 18 - 45 years old; Submitted to a social security regimen; Agreeing to the study & Informed consent form signed; Body mass index ([weight (kg)/height (m)]²) < 27; No treatment received 6 weeks before inclusion; No anomaly after: complete clinical examination, pulse measurement, ECG; Blood pressure on AMBP : Mean systolic blood pressure < 135 mmHg & Mean diastolic blood pressure < 85 mmHg No biological abnormality after biological testing o No participation in a clinical trial 3 months before inclusion. Exclusion Criteria: Subject not agreeing to the study or impossible to follow-up; Known history of significant medical or surgical pathology, notably endocrine; Renal or hepatic insufficiency; Nephrotic syndrome; Edematous syndrome; Hypertension or postural hypotension; Cardiac rhythm or conduction pathologies; Cardiac insufficiency; Epilepsy; Significant psychiatric disorder; Known history of severe allergy, hypersensitivity to metoclopramide; Hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase deficit; Impaired lactose tolerance.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L-lysine<br>11 days treatment with study drug, order of periods (active treatment or placebo) being sorted out. | Dietary Supplement: L-lysine<br>* L-lysine, 4,95 G at day : 0,55 G 3 times a day, orally, during meals<br>|
| Placebo Comparator: placebo<br>11 days treatment with study drug, order of periods (L-lysine or placebo) being sorted out. | Dietary Supplement: placebo<br>* placebo, 3 times a day, orally, during meals<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma aldosterone variation during orthostatic test |  | Day 5 of treatment, at each period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Basal aldosterone alteration; Aldosterone variation during metoclopramide & salt-free diet tests; Basal and stimulated (3 different tests) alterations of renin, cortisol & ACTH |  | Day 5, 6, 7 and 11 of treatment, at each period | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Aldosterone, L-lysine, Cortisol, Adrenal glands