Effects of L-lysine on Adrenal Secretion (L-Lysine)

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Male
• Intervention / Treatment: Dietary supplement: L-lysine; Dietary supplement: placebo

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

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Rouen, France, 76031
    • Rouen Clinical research Centre (CIC 0204)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University Hospital, Rouen
• Investigators: Principal Investigator: Hervé Lefebvre, PHD, Rouen University Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: October 11, 2010
• First Submitted That Met QC Criteria: October 12, 2010
• First Posted (Estimate): October 13, 2010

Study Record Updates

• Last Update Posted (Estimate): June 18, 2013
• Last Update Submitted That Met QC Criteria: June 17, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Cortisol; Aldosterone; L-lysine; Adrenal glands
• Other Study ID Numbers: 2008/138/HP