Kinetic of Melatonin Subsequent to the Consumption of Melatonin-rich Food Supplements

Randomized, Open-label Bioavailability Study of the Kinetics of Plasma, Urinary and Salivary Concentrations of Melatonin and 6-sulfatoxymelatonin Subsequent to the Consumption of Melatonin-rich Food Supplements With Different Galenic Forms

This study is conducted to clinically document the melatonin bioavailability of two dietary supplements containing melatonin : one prolonged release tablet dosed at 1.9mg and one spray dosed at 1mg for 2 oral sprays.

Study Overview

• Status: Completed
• Conditions: Melatonin Bioavailability
• Intervention / Treatment: Dietary supplement: a prolonged release tablet and a spray containing melatonin

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Dijon, France, 21000
    • CIC CEN EXPERIMENTAL / CEN Nutriment

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 between the ages of 18 and 45,
• In good general health, i.e., free of chronic conditions and not taking medication at the time of inclusion and/or long-term,
• Over 70 kg and with a body mass index between 18.5 and 24.9,
• Able and willing to participate in the research by complying with the procedures of the protocol, in particular concerning the taking of the product under study and the performance of sequential blood tests,
• Having freely signed the consent form after adequate information on the proposed study, in accordance with Good Clinical Practice and after submission of the information leaflet,
• Affiliated to a social security scheme or similar.

Exclusion Criteria:

• Smoker,
• Drug addict,
• Subject with an alcohol consumption of more than 2 glasses per day,
• Taking a drug treatment or melatonin or a product containing melatonin within 48 hours prior to a kinetics visit,
• Known organic or functional abnormality of the urinary tree,
• Any medical condition that would involve a change in melatonin metabolism:

Drug intake: Fluvoxamine, 5- or 8-methoxypsoralen, cimetidine, carbamazepine and rifampicin, analgesics, Liver abnormality known or detected at the screening visit and judged to be clinically significant by the investigator, Known autoimmune disease,

• Subject assessed as "moderately" or "definitely" evening type,
• Known hypertension (>140/90),
• Diagnosis of migraine by a health professional according to the International Headache Society (IHS) criteria revised in 2004,
• Wuth a sleep disorder,
• Thyroid dysfunction, hyperglycemia or anemia judged to be clinically significant by the investigator,
• Blood donation within one month prior to inclusion,
• A known organic or psychological abnormality (including a history of severe depression) that may bias the results of the study as judged by the investigator,
• Workers with atypical working hours (night work, staggered working hours),
• Known allergy or intolerance to any of the components of the product,
• Psychological or linguistic inability to understand and sign informed consent,
• Participant in another interventional clinical trial or during a period of exclusion from a previous clinical trial,
• Under legal protection (guardianship, curatorship) or deprived of his rights as a result of the administrative or judicial decision,
• Subject who has reached the maximum threshold for compensation for research provided for in the regulations.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: spray before tablet	Dietary supplement: a prolonged release tablet and a spray containing melatonin; prolonged release tablet is dosed at 1.9mg and spray is dosed at 1mg for 2 oral sprays.
Experimental: tablet before spray	Dietary supplement: a prolonged release tablet and a spray containing melatonin; prolonged release tablet is dosed at 1.9mg and spray is dosed at 1mg for 2 oral sprays.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
evolution of the plasma melatonin concentration	the change in plasma melatonin concentration	over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
evolution of the plasma concentration of 6-sulfatoxymelatonin	the change in plasma 6-sulfatoxymelatonin concentration	over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray.
evolution of the urinary concentration of 6-sulfatoxymelatonin	the change in urinary 6-sulfatoxymelatonin concentration	over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray.
evolution of the salivary concentration of melatonin	the change in salivary melatonin concentration	over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray.
adverse events	adverse events	during study participation, maximum 45 days
plasma melatonin AUC	Area Under the Curve of plasma melatonin	over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray.
plasma 6-sulfatoxymelatonin AUC	Area Under the Curve of plasma 6-sulfatoxymelatonin	over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray.
urinary 6-sulfatoxymelatonin AUC	Area Under the Curve of urinary 6-sulfatoxymelatonin	over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray.
salivary melatonin AUC	Area Under the Curve of salivary melatonin	over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray.
plasma melatonin Cmax	Peak concentration of plasma melatonin	over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray.
plasma 6-sulfatoxymelatonin Cmax	Peak concentration of plasma 6-sulfatoxymelatonin	over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray.
urinary 6-sulfatoxymelatonin Cmax	Peak concentration of urinary 6-sulfatoxymelatonin	over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray.
salivary melatonin Cmax	Peak concentration of salivary melatonin	over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray.
plasma melatonin Tmax	Time take to reach Cmax of plasma melatonin	over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray.
plasma 6-sulfatoxymelatonin Tmax	Time take to reach Cmax of plasma 6-sulfatoxymelatonin	over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray.
urinary 6-sulfatoxymelatonin Tmax	Time take to reach Cmax of urinary 6-sulfatoxymelatonin	over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray.
salivary melatonin Tmax	Time take to reach Cmax of salivary melatonin	over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray.
plasma melatonin half life	time required for the concentration of plasma melatonin to decrease to half of its starting dose	over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray.
plasma 6-sulfatoxymelatonin half life	time required for the concentration of plasma 6-sulfatoxymelatonin to decrease to half of its starting dose	over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray.
urinary 6-sulfatoxymelatonin half life	time required for the concentration of urinary 6-sulfatoxymelatonin to decrease to half of its starting dose	over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray.
salivary melatonin half life	time required for the concentration of salivary melatonin to decrease to half of its starting dose	over 540 minutes after taking the sustained-release tablet and 420 minutes after taking the spray.

Collaborators and Investigators

• Sponsor: PiLeJe

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2020
• Primary Completion (Actual): October 5, 2020
• Study Completion (Actual): October 5, 2020

Study Registration Dates

• First Submitted: July 27, 2020
• First Submitted That Met QC Criteria: September 28, 2020
• First Posted (Actual): October 5, 2020

Study Record Updates

• Last Update Posted (Actual): March 22, 2021
• Last Update Submitted That Met QC Criteria: March 19, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: Pil-Clin-Melat-020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: no sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No