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

NCT06617351 | Not Yet Recruiting

• 1 other identifier: STUDY00006674
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Cell Migration; Cell Invasion; Exercise Recovery

Keywords

melatonin; exercise recovery

Outcome Measures

Primary Outcomes (51)

• Subjective Sleep Duration

  Participants provide information about sleep duration the previous night using the Hooper Questionnaire administered via pen and paper. Response is rated on a seven-point Likert scale with the following responses: * 10+ * 9-10 * 8-9 * 8 * 7-8 * 5-7 * 5 or less

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Subjective Sleep Quality

  Participants provide information about their sleep quality the previous night using the Hooper Questionnaire administered via pen and paper. Response is rated on a seven-point Likert scale with the following responses: * Outstanding * Very good * Good * Better than normal * Worse than normal * Disrupted * Horrible - No Sleep

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Subjective Fatigue

  Participants provide information about their current level of fatigue using the Hooper Questionnaire administered via pen and paper. Response is rated on a seven-point Likert scale with the following responses: * No Fatigue * Minimal Fatigue * Better than normal * Normal * Worse than normal * Very Fatigued * Exhausted - Major fatigue

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Subjective Muscle Soreness

  Participants provide information about their current level of muscle soreness using the Hooper Questionnaire administered via pen and paper. Response is rated on a seven-point Likert scale with the following responses: * No Soreness * Very little soreness * Better than normal * Normal * Worse than normal * Very sore/tight * Extremely sore/tight

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Subjective Mental Stress

  Participants provide information about their current level of mental stress using the Hooper Questionnaire administered via pen and paper. Response is rated on a seven-point Likert scale with the following responses: * Feeling great - Very relaxed * Feeling Good - Relaxed * Better than normal * Normal * Worse than normal * Stressed * Very Stressed

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Perceived Recovery Status

  Participants provide information about their perceived recovery status using the Perceived Recovery Status Scale (PRSS). Response is rated on a scale ranging from 0 (very poorly recovered/extremely tired) to 10 (very well recovered/highly energetic). Each response also corresponds to a broader performance categorization with values indicating expectations of either declined performance, similar performance, or improved performance relative to subsequent time points.

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Active Range of Motion (AROM)

  Assessed in both lower limbs via handheld goniometer while participant is supine. Average of two measures on each limb is used to determine AROM.

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Pain Pressure Threshold (PPT)

  Assessed in dominant lower limb via manual algometer while participant is supine. PPT is defined as the point at which the pressure applied via the algometer becomes uncomfortable, as verbally indicated by the participant. PPT is measured in triplicate with 10 seconds of rest between measurements. Average of the three measures is used to determine PPT.

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Peak Jump Height

  Determined via counter movement jump performed using portable force plate system. Peak Jump height is the highest jump height across 3 jumps separated by 30 seconds.

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Mean Jump Height

  Determined via counter movement jump performed using portable force plate system. Mean Jump height is the average jump height across 3 jumps separated by 30 seconds.

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Peak Jump Force

  Determined via counter movement jump performed using portable force plate system. Peak force is the highest force achieved across 3 jumps separated by 30 seconds.

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Mean Jump Force

  Determined via counter movement jump performed using portable force plate system. Mean Jump force is the average jump force across 3 jumps separated by 30 seconds.

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Peak Braking Force

  Determined via counter movement jump performed using portable force plate system. Peak braking force is the highest braking force achieved across 3 jumps separated by 30 seconds.

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Mean Braking Force

  Determined via counter movement jump performed using portable force plate system. Mean braking force is the average braking force across 3 jumps separated by 30 seconds.

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Peak Braking Rate of Force Development (RFD)

  Determined via counter movement jump performed using portable force plate system. Peak braking rate of force development force is the peak braking RFD force achieved across 3 jumps separated by 30 seconds.

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Mean Braking Rate of Force Development (RFD)

  Determined via counter movement jump performed using portable force plate system. Mean braking rate of force development is the average braking RFD force across 3 jumps separated by 30 seconds.

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Mean Reactive Strength Index (RSI)

  Determined via counter movement jump performed using portable force plate system. Defined as the time taken to complete the flight phase divided by the total time taken from the initiation of movement to the instant of take-off. Mean RSI is the average RSI across 3 jumps separated by 30 seconds.

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Peak Reactive Strength Index (RSI)

  Determined via counter movement jump performed using portable force plate system. Defined as the time taken to complete the flight phase divided by the total time taken from the initiation of movement to the instant of take-off. Peak RSI is the peak RSI achieved across 3 jumps separated by 30 seconds.

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Squat Maximal Voluntary Isometric Contraction (MVIC) Force

  Determined via isometric squat contraction using portable force plate system and isometric squat rack with fixed bar. Participants will complete three 5-second isometric contractions with one minute of rest between contractions. The highest force achieved during the three contractions will be recorded as Squat MVIC force.

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Squat Maximal Voluntary Isometric Contraction (MVIC) Rate of Force Development (RFD)

  Determined via isometric squat contraction using portable force plate system and isometric squat rack with fixed bar. Participants will complete three 5-second isometric contractions with one minute of rest between contractions. Rate of force development (RFD), dictated by the onset of muscular contraction, will be recorded at 0-300ms for the contraction with the highest peak force.

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Objective Sleep Quality

  Assessed using an ActiGraph GT9X Link accelerometer. Participants will wear the accelerometer and beginning 24 hours before the resistance exercise protocol through 48-hours post-exercise. Number of minutes that participants are asleep, and the number of times their sleep is disrupted will be assessed.

  -24 hours before (-24H), 24-hours Post (24H), 48-hours Post (48H)

• Physical Activity

  Assessed using an ActiGraph GT9X Link accelerometer. Participants will wear the accelerometer and beginning 24 hours before the resistance exercise protocol through 48-hours post-exercise. Minutes per day that participants engage in low, moderate, and high intensity physical activity will be assessed.

  -24 hours before (-24H), 24-hours Post (24H), 48-hours Post (48H)

• Hematocrit

  Assessed via Automated Hematology Analyzer

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Hemoglobin

  Assessed via Automated Hematology Analyzer

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Mean corpuscular volume (MCV)

  Assessed via Automated Hematology Analyzer

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Mean corpuscular hemoglobin (MCH)

  Assessed via Automated Hematology Analyzer

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Mean corpuscular hemoglobin concentration (MCHC)

  Assessed via Automated Hematology Analyzer

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Total white blood cell count (WBC)

  Assessed via Automated Hematology Analyzer

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Total red blood cell count (RBC)

  Assessed via Automated Hematology Analyzer

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Lymphocyte Count

  Assessed via Automated Hematology Analyzer

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Monocyte Count

  Assessed via Automated Hematology Analyzer

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Granulocyte Count

  Assessed via Automated Hematology Analyzer

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Platelet Count

  Assessed via Automated Hematology Analyzer

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Serum Creatine Kinase (CK) concentration

  Marker of muscle damage. Assessed via assay and microplate reader

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Serum Melatonin concentration

  Assessed via assay and microplate reader

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Serum C-reactive protein (CRP) concentration

  Assessed via assay and microplate reader

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Serum Interleukin-8 (IL-8) concentration

  Assessed via assay and microplate reader

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Serum Monocyte Chemoattractant Protein-1 (MCP-1) concentration

  Assessed via assay and microplate reader

  Pre (0), Immediately-post (IP), 4-hours Post (4H), 24-hours post (24H), 48-hours post (48H)

• Monocyte Cell Index (CI)

  Assessed via Real Time Cell Analysis (RTCA) assay

  Pre (0), 24-hours post (24H), 48-hours post (48H)

• Neutrophil Cell Index (CI)

  Assessed via Real Time Cell Analysis (RTCA) assay

  Pre (0), 4-Hours Post (4H), 24-hours post (24H)

• Monocyte C-C chemokine receptor 2 (CCR2) expression

  Assessed via flow cytometry

  Pre (0), 24-hours post (24H), 48-hours post (48H)

• Monocyte Macrophage-1 antigen (Integrin CD11b) expression

  Assessed via flow cytometry

  Pre (0), 24-hours post (24H), 48-hours post (48H)

• Monocyte Melatonin Receptor 1A (MLTr1A) expression

  Assessed via flow cytometry

  Pre (0), 24-hours post (24H), 48-hours post (48H)

• Neutrophil Receptor 1A (MLTr1A) expression

  Assessed via flow cytometry

  Pre (0), 4-Hours Post (4H), 24-hours post (24H)

• Neutrophil Macrophage-1 antigen (Integrin CD11b) expression

  Assessed via flow cytometry

  Pre (0), 4-Hours Post (4H), 24-hours post (24H)

• Neutrophil Interleukin-8 receptor (CXCR2) expression

  Assessed via flow cytometry

  Pre (0), 4-Hours Post (4H), 24-hours post (24H)

• Diet - Daily Protein

  Assessed via Automated Self-Administered 24hr Dietary Recall (ASA24).

  Pre (0), 24-hours Post (24H), 48-hours Post (48H)

• Diet - Daily Carbohydrate

  Assessed via Automated Self-Administered 24hr Dietary Recall (ASA24).

  Pre (0), 24-hours Post (24H), 48-hours Post (48H)

• Diet - Daily Fat

  Assessed via Automated Self-Administered 24hr Dietary Recall (ASA24).

  Pre (0), 24-hours Post (24H), 48-hours Post (48H)

• Diet - Daily Total Calories

  Assessed via Automated Self-Administered 24hr Dietary Recall (ASA24).

  Pre (0), 24-hours Post (24H), 48-hours Post (48H)

• Diet - Daily Total Micronutrients

  Assessed via Automated Self-Administered 24hr Dietary Recall (ASA24). Participants report each eating occasion and the time of consumption during a 24-hour period.

  Pre (0), 24-hours Post (24H), 48-hours Post (48H)

Study Arms (2)

Melatonin

EXPERIMENTAL

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.

Dietary Supplement: Melatonin

Placebo

PLACEBO COMPARATOR

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.

Dietary Supplement: Placebo

Interventions

Melatonin DIETARY_SUPPLEMENT

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

Melatonin

Placebo DIETARY_SUPPLEMENT

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

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• Individual does not agree to participate in this study.
• 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.

Sponsors & Collaborators

• University of Central Florida: lead

Study Sites (1)

Kinesiology Research Labs

Orlando, Florida, 32816, United States

Location

Related Publications (10)

• 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.

  PMID: 27384580 BACKGROUND

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

  PMID: 10358769 BACKGROUND

• 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.

  PMID: 19098520 BACKGROUND

• 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.

  PMID: 17485518 BACKGROUND

• 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.

  PMID: 15230868 BACKGROUND

• 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.

  PMID: 8077674 BACKGROUND

• 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.

  PMID: 23889107 BACKGROUND

• 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.

  PMID: 22212240 BACKGROUND

• 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.

  PMID: 17956623 BACKGROUND

• 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.

  PMID: 21615492 BACKGROUND

MeSH Terms

Interventions

Melatonin

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Central Study Contacts

Adam J Wells, PhD

CONTACT

407-823-3906; adam.wells@ucf.edu

Kadie Drahos, BS

CONTACT

716-946-1619; kadie.drahos@ucf.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Kinesiology

Study Record Dates

• First Submitted: September 24, 2024
• First Posted: September 27, 2024
• Study Start: October 1, 2024
• Primary Completion: March 31, 2025
• Study Completion: July 31, 2025
• Last Updated: October 1, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)