Oral Bioavailability of Two Melatonin Supplements

Study Overview
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Brief Summary
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Results from several clinical studies show that orally administered melatonin has low bioavailability and a very short half-life. Phenyl capsaicin, a synthetic analogue of capsaicin, might increase its bioavailability by inhibiting the enzymes involved in its hepatic metabolism. Thus, the hypothesis of the present study is that the administration of melatonin supplement with phenyl capsaicin presents greater bioavailability than a melatonin supplement that does not contain phenyl capsaicin.

Detailed Description
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Melatonin is an endogenous indolamine that regulates many physiological functions such as reproduction, temperature, mood, bone growth or the immune system. However, since its production is closely related to the light/dark cycle, melatonin is considered one of the main chronobiotic agents that modulates circadian rhythms. For this reason, in recent years there has been increased interest in the exogenous use of melatonin to address problems of insomnia and circadian rhythm disorders such as jet lag syndrome or shift work. Although many studies have demonstrated the effectiveness of melatonin in treating sleep disorders, pharmacokinetic studies show that it has poor oral bioavailability and a very short half-life. So, new strategies and studies are necessary to increase the low bioavailability of melatonin. In this context, it has been shown that phenyl capsaicin, a synthetic analogue of capsaicin, might increase melatonin's bioavailability by inhibiting Cytochrome P450 liver enzymes, which are involved in its metabolism. Therefore, the main objective of this study is to quantify and compare the oral bioavailability between a melatonin supplement with phenyl capsaicin and another melatonin supplement that does not contain phenyl capsaicin. The secondary objectives of the study are to determine the pharmacokinetic parameters: Maximum plasma concentration (Cmax). Time for maximum plasma concentration (Tmax). Half-life (T1/2). Area Under the Curve (AUC 0-inf) of plasma melatonin levels During the study there will be 3 visits: a preselection visit (V0), a visit for the first postprandial study (V1) and after one week washing period, a visit for the second postprandial study (V2).

Official Title
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Interventional Study for the Comparison of the Oral Bioavailability of Two Melatonin Supplements

Conditions
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Bioavailability

Intervention / Treatment
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* Dietary Supplement: Melatonin with phenyl capsaicin
* Dietary Supplement: Melatonin without phenyl capsaicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women between 18 and 65 years old. Sign the informed consent form. Know how to read, write and speak Catalan or Spanish. Exclusion Criteria: 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 (e.g. L-Tryptophan or melatonin) Present intolerances and/or food allergies related to melatonin, phenyl capsaicin, microcrystalline cellulose or silicon dioxide . Be a smoker. Having received antibiotic treatment up to 30 days before the start of the study. Present values of body mass index ≤ 18kg/m^2 or ≥ 35 kg/m^2. Present some chronic disease with clinical manifestations: coronary heart disease, cardiovascular disease, diabetes mellitus, hypertension, ulcerative colitis, celiac disease, Crohn's disease, chronic kidney disease, cancer, benign prostatic hyperplasia, autoimmune diseases (such as fibromyalgia), respiratory and/or gastrointestinal diseases that may compromise the absorption of the compound. Clinical history of anemia. Being pregnant or intending to became pregnant. Be in breastfeeding period. Being unable to follow the study guidelines. Participate in or have participated in a clinical trial or nutritional intervention study in the last 30 days before inclusion in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Crossover, Randomized, Triple-Blind Study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Melatonin with phenyl capsaicin<br>Participants will consume one capsule of 1 mg of melatonin with phenyl capsaicin | Dietary Supplement: Melatonin with phenyl capsaicin<br>* Blood samples will be collected at different time points following the oral administration of the melatonin supplement with phenyl capsaicin<br>|
| Active Comparator: Melatonin without phenyl capsaicin<br>Participants will consume one capsule of 1 mg of melatonin without phenyl capsaicin | Dietary Supplement: Melatonin without phenyl capsaicin<br>* Blood samples will be collected at different time points following the oral administration of the melatonin supplement without phenyl capsaicin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bioavailability of melatonin calculated by the Area Under The Curve (AUC 0-6) of plasma melatonin levels | Fasting melatonin levels in plasma will be determined before consuming the melatonin supplement until 6 hours postprandially at 7 points after consuming the capsule (15 min., 30 min., 45 min., 1h., 2h., 4h and 6h). The melatonin levels in plasma will be quantified by Liquid Chromatography coupled with Tandem Mass Spectrometry (LC-MS/MS) | At week 1 | 
| Bioavailability of melatonin calculated by the Area Under The Curve (AUC 0-6) of plasma melatonin levels | Fasting melatonin levels in plasma will be determined before consuming the melatonin supplement until 6 hours postprandially at 7 points after consuming the capsule (15 min., 30 min., 45 min., 1h., 2h., 4h and 6h). The melatonin levels in plasma will be quantified by Liquid Chromatography coupled with Tandem Mass Spectrometry (LC-MS/MS) | At week 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) | Maximum plasma concentration of melatonin | At week 1 | 
| Maximum plasma concentration (Cmax) | Maximum plasma concentration of melatonin | At week 3 | 
| Time for maximum plasma concentration (Tmax) | Time period for the maximum plasma concentration of melatonin | At week 1 | 
| Time for maximum plasma concentration (Tmax) | Time period for the maximum plasma concentration of melatonin | At week 3 | 
| Half-life (T1/2) | Time taken for half the initial dose of melatonin administered to be eliminated from the body | At week 1 | 
| Half-life (T1/2) | Time taken for half the initial dose of melatonin administered to be eliminated from the body | At week 3 | 
| Area Under the Curve (AUC 0-inf) to infinite time of plasma melatonin levels | AUC 0-inf extrapolates the area to infinite time and measures the total melatonin exposure across time. | At week 1 | 
| Area Under the Curve (AUC 0-inf) to infinite time of plasma melatonin levels | AUC 0-inf extrapolates the area to infinite time and measures the total melatonin exposure across time. | At week 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melatonin, Phenyl capsaicin, Bioenhancer