Clinical trial NCT03951025: Study of the Bioavailability of a Food Supplement Rich in Melatonin Administered Sublingually and Orally (MELATONIN)
Official title: Study of the Bioavailability of a Food Supplement Rich in Melatonin Administered Sublingually Compared to Its Oral Administration. Randomized, Crossover, Single-blind Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Biological Availability
Keywords: melatonin
oral administration
sublingual administration
Lead sponsor: Technological Centre of Nutrition and Health, Spain
Sponsor class: OTHER
Collaborators: name: Fundació Eurecat
name: Hospital Universitari Sant Joan de Reus
name: Plantas Medicinales y Complementos Alimenticios (PLAMECA), S.A.
name: University Rovira i Virgili
First posted: 2019-05-15
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. 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.
2. Present intolerances and / or food allergies related to melatonin.
3. Presenting anemia (hemoglobin ≤ 13 g/dL in men and ≤ 12 g/dL in women).
4. Being pregnant or intending to become pregnant.
5. Be in breastfeeding period.
6. Be a smoker
7. Participate in or have participate in a clinical trial or nutritional intervention study in the last 30 days prior to inclusion in the study.

Primary outcomes:
measure: Bioavailability of melatonin calculated by the Area Under The Curve (AUC)
timeFrame: 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:
measure: Maximum plasma concentration (Cmax)
timeFrame: 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.
measure: Time for maximum plasma concentration (Tmax)
timeFrame: 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.
measure: Half-life (T1/2)
timeFrame: 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.
measure: Melatonin urine levels
timeFrame: At week 1 and week 2. Urine at basal time and at 3 hours and 6 hours after tablet consumption.
Other outcomes:
Locations:
city: Reus
country: Spain
facility: Centro Tecnológico de Nutrición y Salud (Eurecat-Reus)
state: Tarragona
Study officials:
affiliation: Centro Tecnológico de Nutrición y Salud (Eurecat_Reus). Reus, Tarragona, Spain.
name: Rosa Solà, Dr
role: PRINCIPAL_INVESTIGATOR
References: