The Effects of Acute Melatonin Supplementation on Cardiovascular Responses to Sympathetic Activation

Study Overview
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Brief Summary
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the purpose of this experiment is to determine if acute melatonin supplementation alters central and peripheral cardiovascular responses to a cold pressor test at rest and during dynamic exercise.

Detailed Description
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After IRB approval, experiments will take place in the Human Circulation Research Laboratory in the Department of Health and Exercise on the University of Oklahoma Norman campus. All subjects will complete a total of 3 visits. The first is a screening visit to provide informed consent and to ensure the potential participant meets all inclusion criteria and no exclusion criteria. Once consented and enrolled, participants will be familiarized with experimental protocols. On separate days (visits 2 and 3), participants will complete placebo (PLA) and melatonin (MEL) in a randomly ordered, single-blind, counter-balanced design. PLA or MEL treatment will precede testing by 30min to maximize absorption into the circulation (Bartoli, 2013). All experiments (PLA/MEL) will begin with the subject lying supine for 5 min of quiet rest where baseline measurements are taken, followed by activation of the lower body negative pressure (LBNP) device causing suction at -20 mmHg. Following LBNP participants will be given 10 minutes of rest to recover all variables to pre-LBNP values. After which participants will be given a hand grip dynamometer to complete 7 minutes of exercise at an intensity of 20% MVC at a 1s contraction to 2s relaxation cycle paced by a metronome. During the final 2 minutes of the 7 minutes of exercise the LBNP device will be activated again to -20mmHg such that the participant will be completing LBNP during rhythmic grip exercise. After the completion of exercise, the subject will remain supine for 10min. Then the a Total Labile Signal (TLS) procedure will be conducted. Where the experimental limb is occluded using a blood pressure cuff for 5min. The cuff is then rapidly deflated. The lowest oxyhemoglobin measured during the occlusion is recorded. After the TLS procedure, the subject will be de-instrumented and will leave the laboratory.

Official Title
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The Effects of Acute Melatonin Supplementation on Cardiovascular Responses to Sympathetic Activation

Conditions
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Healthy

Intervention / Treatment
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* Dietary Supplement: melatonin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men and women Women must be premenopausal with a regular menstrual cycle (26-30 days) Exclusion Criteria: History of autonomic dysfunction Cardiovascular diseases Diabetes Tobacco/nicotine use Systolic Pressure >= 130 mmHg Diastolic Pressure >= 85 mmHg Regular melatonin use >= 1 use/week Allergy to melatonin Cardiometabolic medication use (e.g. anti-hypertensives, insulin-sensitizing, statins) Sex hormone replacement medical use (e.g. testosterone, estrogen, progesterone) Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This study is a single-blind crossover design.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo (PLA) is 10 sublingual sprays of a diluted (1 microliter/29ml filtered water) mint extract. | Other: Placebo<br>* 10 sprays of diluted mint extract. This mimics the sensation and taste of the melatonin spray<br>|
| Experimental: Melatonin<br>5mg commercially available melatonin (MEL) spray will be given sublingually. | Dietary Supplement: melatonin<br>* A 5mg dose of melatonin spay will be delivered sublingually.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle Tissue Oxygenation | Concentrations of Total, Oxy, and deoxyhemoglobin of Flexor Digitorum Profundus muscle of the forearm | 7 minutes of rest and 7 minutes of exercise | 
| Mean Arterial Pressure | average pressure within the arteries | 7 minutes of rest and 7 minutes of exercise | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral Oxygenation | Concentrations of Total, Oxy, and deoxyhemoglobin of the Prefrontal Cortex of the brain | 7 minutes of rest and 7 minutes of exercise | 
| Heart Rate | number of heart beats per minute | 7 minutes of rest and 7 minutes of exercise | 
| Respiratory Rate | number of breaths per minute | 7 minutes of rest and 7 minutes of exercise | 
| Cardiac Output | volume of blood pumped by the heart per minute | 7 minutes of rest and 7 minutes of exercise | 
| Stroke Volume | volume of blood pumped by the heart per heart beat | 7 minutes of rest and 7 minutes of exercise | 
| Total peripheral resistance | amount of force affecting resistance to blood flow throughout the circulatory system | 7 minutes of rest and 7 minutes of exercise | 
| Heart Rate Variability | measure of the variation in time between each heart beat | 7 minutes of rest and 7 minutes of exercise |