This Repeated Measures Parallel-group Investigation Will Examine the Influence of Short-term Melatonin Supplementation (5mg, 3 x Day for 72 Hours) on Cellular Responses, Functional Performance and Recovery Following an Acute Bout of Dynamic Resistance Exercise in Resistance Trained Men and Women

NCT ID: NCT06617351

Last Updated: 2024-10-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-10-01

Study Completion Date

2025-07-31

Brief Summary

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Oral Melatonin is a commercially available product available alone and as a constituent in a number of supplements. Previous research suggests that short-term supplementation with oral melatonin may amplify the recovery response to damaging resistance exercise via modulation of subsequent immune and inflammatory responses. However the effects of oral melatonin on neutrophil and monocyte invasion/migration, a critical step in the resolution of skeletal muscle tissue homeostasis, has not been examined. An oral melatonin supplement (5mg) will be provided three times daily beginning 24-hours before and ending 48-hours after an acute bout of damaging resistance exercise (total 15mg/day for 3 days).

Goals:

1. To investigate the effect of melatonin on systemic and cellular responses following an acute bout of damaging resistance exercise.
2. To investigate the effect of melatonin on measures of functional performance before and during recovery from an acute bout of damaging resistance exercise.

Detailed Description

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Resistance exercise of sufficient intensity can result in localized damage to skeletal muscle tissue. The resolution of tissue homeostasis following damaging exercise is mediated largely by neutrophils and monocytes of the innate immune system (1). Neutrophils and monocytes originate in the systemic circulation and infiltrate the damaged tissue following activation and migration in response to damage associated molecular cues. These cells are reported to execute a number of processes fundamental to recovery, including the phagocytosis of opsonized cellular debris (2), and secretion of mitogenic factors that stimulate both the proliferation and differentiation of myogenic precursor cells (3). Disruption of this cellular response has been shown to lead to impaired muscle regeneration, and a subsequent deficit in muscle fiber size (4). Accordingly, a successful innate immune response is paramount for optimal tissue regeneration.

Several supplements have been introduced to the market with purported claims of enhanced recovery from exercise. One potential mechanism for enhanced recovery is through augmentation of the immune response, which may allow for a more pronounced stimulus to enhance repair (1). Previous research suggests that short-term supplementation with melatonin, an endogenously produced indoleamine, may amplify the recovery response. Melatonin receptors are expressed on most immune cell types, including monocytes, neutrophils, and Th1 lymphocytes (5). Melatonin has previously been shown to activate monocytes (6), and treatment with melatonin has been shown to upregulate the recruitment of human monocytes through interaction with the melatonin receptor (MLTr) in vitro. Melatonin has also been shown to alter cytokine production and increase the production of cells of both the innate and adaptive immune system (7). Binding of melatonin to MLTr's expressed on immune cells may modulate recruitment of these cells to damaged tissue, which may in turn regulate the ensuing recovery response. Theoretically, this could reduce recovery time following damaging exercise, improving quality of training and potentially allow for enhanced performance over time (8,9,10). Nevertheless, the effect of short-term melatonin supplementation on innate immune cell and inflammatory responses during recovery from resistance exercise has not been examined.

Goals:

1. To assess systemic and cellular responses to an acute bout of resistance exercise between participants ingesting melatonin versus placebo, including creatine kinase (CK), complete blood counts (CBC), serum interleukin-8 (IL-8), serum monocyte chemoattractant protein-1 (MCP-1), serum melatonin, serum C-reactive protein (CRP), cell receptor expression (monocytes: activated CD11b, CCR2, MLTr1A; neutrophils: activated CD11b. CXCR2, MLTr1A), and neutrophil/monocyte invasion/migration dynamics (cell index, CI).
2. To assess functional measures of recovery following an acute bout of resistance exercise between participants ingesting melatonin versus placebo, including subjective sleep quality/duration, fatigue, soreness and stress (Hooper Questionnaire), perceived Recovery (Perceived Recovery Status Scale, PRSS), active range of motion (AROM), pain pressure threshold (PPT), countermovement jump (CMJ), squat maximal voluntary isometric contraction (MVIC), and objective sleep and physical activity (Accelerometry).

Method:

Randomized, double-blind, placebo controlled parallel-groups trial comparing the effect of supplementation with Melatonin versus Placebo on systemic and cellular responses and functional recovery from damaging resistance exercise.

Melatonin or placebo supplementation (randomly assigned) will occur over a period of 3 days beginning 24-hours prior to completion of an acute bout of damaging resistance exercise through a 48-hours post-exercise recovery period.

Objective sleep and physical activity (accelerometry) will be assessed 24-hours before (-24H), 24-hours Post (24H) and 48-Hours (48H) post-exercise. Diet (carbohydrates, fats, proteins, total calories and micronutrients) will be assessed at Pre (0), 24H and 48H post-exercise. CBC, CK, IL-8, MCP-1, CRP, Hooper, PRSS, AROM, PPT, CMJ, MVIC and melatonin will be assessed at Pre (0) immediately- post (IP) 4-hours post (4H), 24H and 48H post-exercise. Neutrophil cell index will be assessed at Pre (0), 4H and 24H post-exercise. Monocyte cell index (CI) will be assessed at Pre (0), 24H and 48H post-exercise. Neutrophil cell receptor expression will be assessed at Pre (0), 4H and 24H. Monocyte receptor expression will be assessed at Pre (0), 24H and 48H.

Conditions

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Cell Migration Cell Invasion Exercise Recovery

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Melatonin

Participants will receive Melatonin (5mg, 3 times daily with breakfast, lunch and dinner) beginning 24 hours before and ending 48 hours following an acute bout of dynamic high-intensity resistance exercise. On the day of the exercise bout, participants will ingest a single dose of Melatonin prior to arriving at the lab and following all testing procedures.

Melatonin formula: 7.5 kCal, 2 g Carbohydrate, 1.5 g total sugars, 7.5 mg sodium, 5 mg melatonin.

Group Type EXPERIMENTAL

Melatonin

Intervention Type DIETARY_SUPPLEMENT

Gummy - 7.5 kilocalories (kCal), 2 g Carbohydrate, 1.5 g total sugars, 7.5 mg sodium, 5 mg melatonin.

Placebo

Participants will receive Placebo (3 times daily with breakfast, lunch and dinner) beginning 24 hours before and ending 48 hours following an acute bout of dynamic high-intensity resistance exercise. On the day of the exercise bout, participants will ingest a single dose of the placebo prior to arriving at the lab and following all testing procedures.

Placebo formula: 12.5 kCal, 3g Carbohydrate, 1.875 g total sugars, 1.25 mg sodium.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DIETARY_SUPPLEMENT

Gummy - 12.5 kilocalories (kCal), 3g Carbohydrate, 1.875 g total sugars, 1.25 mg sodium.

Interventions

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Melatonin

Gummy - 7.5 kilocalories (kCal), 2 g Carbohydrate, 1.5 g total sugars, 7.5 mg sodium, 5 mg melatonin.

Intervention Type DIETARY_SUPPLEMENT

Placebo

Gummy - 12.5 kilocalories (kCal), 3g Carbohydrate, 1.875 g total sugars, 1.25 mg sodium.

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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Inclusion Criteria

* Male or female between the ages of 18-40 years old.
* Healthy and ready for physical activity as determined by the Physical Activity Readiness Questionnaire (PAR-Q+) and Medical History Questionnaire (MHQ).
* Active resistance training for a minimum of 6 months as defined by 3 resistance training sessions (muscle strengthening activities such as free weights, weight machines, or calisthenics, etc.) per week with at least one lower body session as determined by the training history questionnaire.
* Premenopausal, with an identifiable onset of menses (early follicular phase) as determined by the menstrual status questionnaire (female participants only)..
* Not currently pregnant and no intention to become pregnant for the duration of participation (female participants only).
* Currently free from and willing to abstain from dietary supplements that are viewed by study investigators to confound the outcomes of the study (e.g., creatine, beta-alanine) for the duration of the study. Participants currently using supplements will be permitted to enroll in the study following a 4-week washout period of these supplements.
* Willing to adhere to all pre-testing visit instructions including abstaining from exercise for the duration of the study and abstaining from alcohol for 24 hours prior to visit 2 as well as for 24 hours before visit 3 until completion of the study.
* Currently be consuming ≤ 300mg caffeine per day on average and willing to keep caffeine intake consistent throughout the duration of the study. Participants must also be willing to abstain from caffeine intake for 12 hours prior to visits 3, 4 and 5 and not consume caffeine the morning of these visits.
* Free from previous or current lower body injuries that are viewed by the investigators to potentially limit ability of the participant to perform the exercise intervention or functional assessments.
* Not regularly taking any type of prescription or over-the-counter medication which might affect the assessments, or having any chronic illnesses, which require medical care.
* Considered by the study investigators to have a high likelihood of successful venipuncture following an initial examination of the participants antecubital fossa by a certified phlebotomist and verbal discussion of the participants blood draw history (including history of unsuccessful venipunctures, known issues with the locating/palpating of veins in the antecubital fossa by a phlebotomist, and whether these difficulties are more apparent on one arm compared to the other).

* Currently taking melatonin
* Regularly taking any type of prescription or over-the-counter medication which might affect the assessments, or having any chronic illnesses, which require medical care.
* Not currently meeting requirements for resistance trained status.
* Current known pregnancy or intent to become pregnant during the study period.
* Not regularly having periods or amenorrheic, as determined by Menstrual Status Questionnaire (MSQ).
* Currently taking any performance-enhancing drug (determined from health and activity questionnaire).
* Currently taking a nutritional supplement viewed by the research team to confound the outcomes of the study and not willing to abstain from taking the supplement during the course of the study or not willing to undergo a 4-week wash-out period prior to participating if required.
* Evaluated as having a low likelihood of successful venipuncture by a certified phlebotomist.

Exclusion Criteria

* Individual does not agree to participate in this study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Central Florida

OTHER

Sponsor Role lead

Responsible Party

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Adam Wells

Associate Professor of Kinesiology

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Kinesiology Research Labs

Orlando, Florida, United States

Site Status

Countries

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United States

Central Contacts

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Adam J Wells, PhD

Role: CONTACT

407-823-3906

Kadie Drahos, BS

Role: CONTACT

716-946-1619

References

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Wells AJ, Hoffman JR, Jajtner AR, Varanoske AN, Church DD, Gonzalez AM, Townsend JR, Boone CH, Baker KM, Beyer KS, Mangine GT, Oliveira LP, Fukuda DH, Stout JR. The Effect of Post-Resistance Exercise Amino Acids on Plasma MCP-1 and CCR2 Expression. Nutrients. 2016 Jul 2;8(7):409. doi: 10.3390/nu8070409.

Reference Type BACKGROUND
PMID: 27384580 (View on PubMed)

Aderem A, Underhill DM. Mechanisms of phagocytosis in macrophages. Annu Rev Immunol. 1999;17:593-623. doi: 10.1146/annurev.immunol.17.1.593.

Reference Type BACKGROUND
PMID: 10358769 (View on PubMed)

Chazaud B, Brigitte M, Yacoub-Youssef H, Arnold L, Gherardi R, Sonnet C, Lafuste P, Chretien F. Dual and beneficial roles of macrophages during skeletal muscle regeneration. Exerc Sport Sci Rev. 2009 Jan;37(1):18-22. doi: 10.1097/JES.0b013e318190ebdb.

Reference Type BACKGROUND
PMID: 19098520 (View on PubMed)

Arnold L, Henry A, Poron F, Baba-Amer Y, van Rooijen N, Plonquet A, Gherardi RK, Chazaud B. Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. J Exp Med. 2007 May 14;204(5):1057-69. doi: 10.1084/jem.20070075. Epub 2007 May 7.

Reference Type BACKGROUND
PMID: 17485518 (View on PubMed)

Pozo D, Garcia-Maurino S, Guerrero JM, Calvo JR. mRNA expression of nuclear receptor RZR/RORalpha, melatonin membrane receptor MT, and hydroxindole-O-methyltransferase in different populations of human immune cells. J Pineal Res. 2004 Aug;37(1):48-54. doi: 10.1111/j.1600-079X.2004.00135.x.

Reference Type BACKGROUND
PMID: 15230868 (View on PubMed)

Morrey KM, McLachlan JA, Serkin CD, Bakouche O. Activation of human monocytes by the pineal hormone melatonin. J Immunol. 1994 Sep 15;153(6):2671-80.

Reference Type BACKGROUND
PMID: 8077674 (View on PubMed)

Calvo JR, Gonzalez-Yanes C, Maldonado MD. The role of melatonin in the cells of the innate immunity: a review. J Pineal Res. 2013 Sep;55(2):103-20. doi: 10.1111/jpi.12075. Epub 2013 Jul 24.

Reference Type BACKGROUND
PMID: 23889107 (View on PubMed)

Maldonado MD, Manfredi M, Ribas-Serna J, Garcia-Moreno H, Calvo JR. Melatonin administrated immediately before an intense exercise reverses oxidative stress, improves immunological defenses and lipid metabolism in football players. Physiol Behav. 2012 Mar 20;105(5):1099-103. doi: 10.1016/j.physbeh.2011.12.015. Epub 2011 Dec 22.

Reference Type BACKGROUND
PMID: 22212240 (View on PubMed)

Nassar E, Mulligan C, Taylor L, Kerksick C, Galbreath M, Greenwood M, Kreider R, Willoughby DS. Effects of a single dose of N-Acetyl-5-methoxytryptamine (Melatonin) and resistance exercise on the growth hormone/IGF-1 axis in young males and females. J Int Soc Sports Nutr. 2007 Oct 23;4:14. doi: 10.1186/1550-2783-4-14.

Reference Type BACKGROUND
PMID: 17956623 (View on PubMed)

Ochoa JJ, Diaz-Castro J, Kajarabille N, Garcia C, Guisado IM, De Teresa C, Guisado R. Melatonin supplementation ameliorates oxidative stress and inflammatory signaling induced by strenuous exercise in adult human males. J Pineal Res. 2011 Nov;51(4):373-80. doi: 10.1111/j.1600-079X.2011.00899.x. Epub 2011 May 26.

Reference Type BACKGROUND
PMID: 21615492 (View on PubMed)

Other Identifiers

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STUDY00006674

Identifier Type: -

Identifier Source: org_study_id

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