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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 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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| L-lysine | Experimental | 11 days treatment with study drug, order of periods (active treatment or placebo) being sorted out. |
|
| placebo | Placebo Comparator | 11 days treatment with study drug, order of periods (L-lysine or placebo) being sorted out. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| L-lysine | Dietary Supplement | L-lysine, 4,95 G at day : 0,55 G 3 times a day, orally, during meals |
|
| Measure | Description | Time Frame |
|---|---|---|
| Plasma aldosterone variation during orthostatic test | Day 5 of treatment, at each period |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hervé Lefebvre, PHD | University Hospital, Rouen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rouen Clinical research Centre (CIC 0204) | Rouen | 76031 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28103616 | Result | Duparc C, Andre C, Menard J, Godouet-Getti B, Wils J, Cailleux AF, Moreau-Grange L, Louiset E, Lefebvre H. l-Lysine Acts as a Serotonin Type 4 Receptor Antagonist to Counteract In Vitro and In Vivo the Stimulatory Effect of Serotonergic Agents on Aldosterone Secretion in Man. Horm Metab Res. 2017 Apr;49(4):269-275. doi: 10.1055/s-0042-122781. Epub 2017 Jan 19. |
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| ID | Term |
|---|---|
| D008239 | Lysine |
| ID | Term |
|---|---|
| D024361 | Amino Acids, Basic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000599 | Amino Acids, Diamino |
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| placebo | Dietary Supplement | placebo, 3 times a day, orally, during meals |
|
| D000601 | Amino Acids, Essential |