Biological AvailabilityPhase 2MELATONINNCT03951025
Study of the Bioavailability of a Food Supplement Rich in Melatonin Administered Sublingually and Orally (MELATONIN)
A Phase 2 study testing Melatonin oral administration and Melatonin sublingual administration in people with Biological Availability, run by Technological Centre of Nutrition and Health, Spain at 1 site in Spain.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Biological Availability
- What is being tested?
- Melatonin oral administration and Melatonin sublingual administration
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteSpain
- Study dates
- 5 Jun 2019to 7 Aug 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Men and women over 18 years of age.
- Firm the informed consent.
Who cannot join
- 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
- Participate in or have participate in a clinical trial or nutritional intervention study in the last 30 days prior to inclusion in the study.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Centro Tecnológico de Nutrición y Salud (Eurecat-Reus)
Reus, Tarragona
About this study
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
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."
Read more
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
- Being tested
- Melatonin oral administration, Melatonin sublingual administration
- Keywords
- melatonin, oral administration, sublingual administration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Melatonin oral administrationDietary supplement
One tablet with1 mg of melatonin and 82 mg of excipients
Melatonin sublingual administrationDietary supplement
One tablet with 1 mg of melatonin and 82 mg of excipients
| Study group | Role | What they receive |
|---|---|---|
| Melatonin oral administration | Active comparator | Consumption of one tablet with 1 mg of melatonin orally Receives: Dietary Supplement: Melatonin oral administration |
| Melatonin sublingual administration | Experimental | Consumption of one tablet with 1 mg of melatonin sublingually Receives: Dietary Supplement: Melatonin sublingual administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Maximum plasma concentration of melatonin. Cmax will be measured by pharmacokinetics formulas from the melatonin values measured at different times (basal and postprandial)
Measured: 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)
Time period for the maximum plasma concentration of melatonin.
Measured: 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)
Time taken for half the initial dose of melatonin administered to be eliminated from the body
Measured: 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
Determination of melatonin and/or its main metabolite 6-sulfatoxymelatonin in urine
Measured: At week 1 and week 2. Urine at basal time and at 3 hours and 6 hours after tablet consumption.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2019
- Study start5 Jun 2019
- Primary completion7 Aug 2019
- Study completion7 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Biological AvailabilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Technological Centre of Nutrition and Health, Spain
- Sponsor type
- University, hospital or other
- Collaborators
- Fundació Eurecat, Hospital Universitari Sant Joan de Reus, Plantas Medicinales y Complementos Alimenticios (PLAMECA), S.A., University Rovira i Virgili
- Responsible party
- Sponsor
- Investigators
- Rosa Solà, Dr, Principal investigator, Centro Tecnológico de Nutrición y Salud (Eurecat_Reus). Reus, Tarragona, Spain.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03951025
- Sponsor's protocol ID
- MELATONIN
- Acronym
- MELATONIN
- Status last verified
- Feb 2022
- First submitted
- 13 May 2019
- Last updated
- 28 Feb 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03951025
- Acronym / sponsor ID
- MELATONIN / MELATONIN
- Conditions
- Biological Availability
- Keywords
- melatonin, oral administration, sublingual administration
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Technological Centre of Nutrition and Health, SpainUniversity, hospital or other
- Collaborators
- Fundació Eurecat, Hospital Universitari Sant Joan de Reus, Plantas Medicinales y Complementos Alimenticios (PLAMECA), S.A., University Rovira i Virgili
- Study start
- 5 Jun 2019 (actual)
- Primary completion
- 7 Aug 2019 (actual)
- Study completion
- 7 Aug 2019 (actual)
- First posted
- 15 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Melatonin oral administration | Active comparator | Dietary Supplement: Melatonin oral administrationConsumption of one tablet with 1 mg of melatonin orally |
| Melatonin sublingual administration | Experimental | Dietary Supplement: Melatonin sublingual administrationConsumption of one tablet with 1 mg of melatonin sublingually |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Men and women over 18 years of age.
- Firm the informed consent.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Melatonin oral administrationOne tablet with1 mg of melatonin and 82 mg of excipients | Dietary supplement | Melatonin oral administration |
| Melatonin sublingual administrationOne tablet with 1 mg of melatonin and 82 mg of excipients | Dietary supplement | Melatonin sublingual administration |
Primary outcome
Bioavailability of melatonin calculated by the Area Under The Curve (AUC)
Time frame: 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.
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.
4 secondary outcomes
Maximum plasma concentration (Cmax)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: At week 1 and week 2. Urine at basal time and at 3 hours and 6 hours after tablet consumption.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rosa Solà, Dr principal investigator
Centro Tecnológico de Nutrición y Salud (Eurecat_Reus). Reus, Tarragona, Spain.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Melatonin oral administration and Melatonin sublingual administration in people with Biological Availability, run by Technological Centre of Nutrition and Health, Spain at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bioavailability of melatonin calculated by the Area Under The Curve (AUC) (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2022.