Study of the Bioavailability of a Food Supplement Rich in Melatonin Administered Sublingually and Orally (MELATONIN)

NCT03951025 | Completed Phase 2

• 1 other identifier: MELATONIN
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

Sleep disorders represent an important public health problem that cause important personal problems, absenteeism and considerable health costs. Although the main drugs used for the treatment of insomnia are still Benzodiazepines and Z-drugs (Zolpidem, Zopiclone, Zaleplon), these are not entirely effective and have numerous side effects that lead to poor compliance with therapy . For the treatment of sleep disorders, alternative non-pharmacological therapies have also been implemented, such as cognitive therapy, relaxation therapy, and the introduction of new agents, including the use of melatonin as a human endogenous molecule with low or zero toxicity. In Europe, the European Food Safety Authority (EFSA) has stated that "A cause and effect relationship is established between the consumption of melatonin and the alleviation of subjective feelings of jet lag. In order to present the declaration of health, the dose of melatonin should be between 0.5 and 5 mg and should be taken close to bedtime on the first day (and subsequent days) of the trip and the following days after arrival at destination.The target population is the general population ". On the other hand, the EFSA states that "A cause and effect relationship is established between the consumption of melatonin and the reduction of sleep onset latency. The Panel considers that to obtain the declared effect, 1 mg of melatonin should be consumed near bedtime. The target population is the general population." The results of several studies in humans show that melatonin administered orally has a low bioavailability (approximately percentage) and a very short half-life. Therefore, it has been suggested that the sublingual route represents an attractive alternative for the administration of compounds that have a low bioavailability, since through this route, the substances are distributed throughout the body avoiding the loss of the compounds by their first-pass metabolism by the liver, as well as the loss by the process of absorption by the digestive system. On this basis the present hypothesis is posed: the administration of melatonin sublingually will have a greater bioavailability than the administration of melatonin orally. The main objective of this study was to quantify the bioavailability of 1 mg of melatonin when administered sublingually and orally.

Conditions

Biological Availability

Keywords

melatonin; oral administration; sublingual administration

Outcome Measures

Primary Outcomes (1)

• Bioavailability of melatonin calculated by the Area Under The Curve (AUC)

  Fasting melatonin blood levels will be determined before consuming the melatonin supplement until 6 hours postprandially at 7 points after consuming the melatonin supplement. The melatonin levels in plasma will be quantified with a Liquid Chromathography (LC)-(ESI+)- Mass Spectrometry (MS)/MS from their pure commercial standard using melatonin-d4 as internal standard.

  At week 1 and week 2. The extraction and bleeding points of melatonin will be at basal time, before taking the tablet and at 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours and 6 hours after tablet intake.

Secondary Outcomes (4)

• Maximum plasma concentration (Cmax)

  At week 1 and week 2. The extraction and bleeding points of melatonin will be at basal time, before taking the tablet and at 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours and 6 hours after tablet intake.

• Time for maximum plasma concentration (Tmax)

  At week 1 and week 2. The extraction and bleeding points of melatonin will be at basal time, before taking the tablet and at 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours and 6 hours after tablet intake.

• Half-life (T1/2)

  At week 1 and week 2. The extraction and bleeding points of melatonin will be at basal time, before taking the tablet and at 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours and 6 hours after tablet intake.

• Melatonin urine levels

  At week 1 and week 2. Urine at basal time and at 3 hours and 6 hours after tablet consumption.

Study Arms (2)

Melatonin oral administration

ACTIVE COMPARATOR

Consumption of one tablet with 1 mg of melatonin orally

Dietary Supplement: Melatonin oral administration

Melatonin sublingual administration

EXPERIMENTAL

Consumption of one tablet with 1 mg of melatonin sublingually

Dietary Supplement: Melatonin sublingual administration

Interventions

Melatonin oral administration DIETARY_SUPPLEMENT

One tablet with1 mg of melatonin and 82 mg of excipients

Melatonin oral administration

Melatonin sublingual administration DIETARY_SUPPLEMENT

One tablet with 1 mg of melatonin and 82 mg of excipients

Melatonin sublingual administration

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women over 18 years of age.
• Firm the informed consent.

You may not qualify if:

• Take supplements or multivitamin supplements or phytotherapeutic products that interfere with the treatment under study up to 30 days before the start of the study.
• Present intolerances and / or food allergies related to melatonin.
• Presenting anemia (hemoglobin ≤ 13 g/dL in men and ≤ 12 g/dL in women).
• Being pregnant or intending to become pregnant.
• Be in breastfeeding period.
• Be a smoker

Sponsors & Collaborators

• Technological Centre of Nutrition and Health, Spain: lead
• Fundació Eurecat: collaborator
• Hospital Universitari Sant Joan de Reus: collaborator
• Plantas Medicinales y Complementos Alimenticios (PLAMECA), S.A.: collaborator
• University Rovira i Virgili: collaborator

Study Sites (1)

Centro Tecnológico de Nutrición y Salud (Eurecat-Reus)

Reus, Tarragona, Spain

Location

Study Officials

• Rosa Solà, Dr

  Centro Tecnológico de Nutrición y Salud (Eurecat_Reus). Reus, Tarragona, Spain.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2019
• First Posted: May 15, 2019
• Study Start: June 5, 2019
• Primary Completion: August 7, 2019
• Study Completion: August 7, 2019
• Last Updated: February 28, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)