Studying Melatonin and Recovery in Teens

NCT06093477 | Recruiting

• 2 other identifiers: IRB-717457K24AR080786-02
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this feasibility clinical trial is to learn if melatonin can help teens having major musculoskeletal surgery by promoting healthy sleep. Melatonin is available as a dietary supplement that may be effective in promoting longer, higher quality sleep. This study will assess the feasibility and acceptability of melatonin for teens undergoing major musculoskeletal surgery, as well as determine optimal measured outcomes (sleep, pain, health-related quality of life) at short- and long-term follow-up.

Conditions

Juvenile; Scoliosis; Scoliosis Idiopathic; Scoliosis; Adolescence; Scoliosis;Congenital; Kyphosis; Spondylolisthesis; Pectus Surgery; Hip Surgery

Keywords

sleep; pain medicine; pediatric pain medicine; melatonin; pilot feasibility trial; acute pain; chronic pain; CPSP; chronic postsurgical pain; spinal fusion surgery; adolescent; perioperative melatonin; hip surgery; pectus surgery

Outcome Measures

Primary Outcomes (4)

• Treatment Adherence

  Youth will self-report daily medication administration on the morning and evening diaries, including the study drug as well as opioid and non-opioid analgesic medications. Medication administration will also be extracted from the EMR during hospitalization. Adherence will be measured as the percentages of doses taken.

  Treatment phase of 14 days before surgery through 21 days after surgery (T2), and 7 days at 3-month follow-up (T3)

• Study Acceptability

  Youth and parent will complete ratings of treatment acceptability using a 5-point scale, ranging from 1 (Strong Dislike or Strongly Disagree) to 5 (Strongly Like or Strongly Agree). A higher score indicates greater study acceptability.

  Assessed one time at Day 21 post-op, and at 3-month follow-up (T3)

• Enrollment and Retention

  Research coordinators will record participant status at each stage including participants approached, assessed for eligibility, invited, consented, randomly assigned, and who received the intended treatment, and completed assessment timepoints, and will collect reasons for declining and dropout. Feasibility metrics will include enrollment rate and attrition rate.

  Pre-treatment (T1), treatment phase of 14 days before surgery through 21 days after surgery (T2), and 7 days at 3-month follow-up (T3)

• Treatment Side Effects

  Youth participants will be asked an open-ended question about side effects they may have experienced from the study drug. The rate of side effects of treatment will be self-reported by participants and extracted from EMR during hospitalization.

  Assessed one time at Day 21 post-op, and at 3-month follow-up (T3)

Secondary Outcomes (6)

• Change in Sleep Quality

  Pre-treatment (T1) and one time at 3-month follow-up (T3)

• Change in Peri-operative Sleep Quality

  Treatment phase of 14 days before surgery through 21 days post-op (T2) and 7 days at 3-month follow-up (T3)

• Change in Sleep Duration

  Treatment phase of 14 days before surgery through 21 days post-op (T2) and 7 days at 3-month follow-up (T3)

• Change in Health-related Quality of Life

  Pre-treatment (T1) and one time at 3-month follow-up (T3)

• Change in Global Pain Severity

  Pre-treatment (T1), one time at Day 21 post-op (T2), and one time at 3-month follow-up (T3)

Other Outcomes (3)

• Adverse Events

  Assessed one time at 3-month follow-up (T3)

• Concomitant therapy

  Assessed one time at 21 days post-op (T2) and one time at 3-month follow-up (T3)

• Pediatric Anxiety

  Assessed one time on day before surgery (T2)

Study Arms (2)

3mg fast-dissolve pill

PLACEBO COMPARATOR

Participants will take a placebo of 3mg fast-dissolve pill (without melatonin), complete surveys, and wear an actigraphy device during the specified study period.

Other: Fast-Dissolve Placebo Pill

3mg fast-dissolve pill (containing melatonin)

EXPERIMENTAL

Participants will take 3mg in fast-dissolve pill form containing the active ingredient melatonin, complete surveys, and wear an actigraphy device during the specified study period.

Dietary Supplement: Fast-Dissolve Melatonin Pill

Interventions

Fast-Dissolve Melatonin Pill DIETARY_SUPPLEMENT

Participants in this arm will take 3mg of melatonin in fast-dissolve pill form daily during the specified study period.

3mg fast-dissolve pill (containing melatonin)

Fast-Dissolve Placebo Pill OTHER

Participants in this arm will take 3mg of placebo in fast-dissolve pill form daily during the specified study period.

3mg fast-dissolve pill

Eligibility Criteria

• Age: 12 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients/youth:
• Age 12-18 years
• Participants undergoing elective major musculoskeletal surgery for eligible conditions
• California state resident
• Regular access to internet and smartphone
• Can read and understand English or Spanish
• Parents/caregivers
• Biological parent or legal guardian of youth
• Can read and understand English or Spanish

You may not qualify if:

• Patients/youth
• Prescription medication for premorbid insomnia
• Cognitive impairment or developmental delay
• Does not agree to a 1-week washout if taking over the counter supplements or other sleep aids prior to the start of the study medication
• High risk for sleep related breathing disorder
• Chronic medical condition that is severe/systemic or requires regular treatment regimen
• Psychiatric admission in prior 30 days
• Patients that underwent major surgery in the last 3 months, or those that have not fully recovered from a prior surgery
• BMI ≥ 99th percentile
• Enrollment in another therapeutic study
• Any serious underlying medical or psychiatric condition, that, in the opinion of the investigator, would contraindicate the patient's participation in the study

Sponsors & Collaborators

• Stanford University: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (1)

Lucile Packard Children's Hospital

Palo Alto, California, 94304, United States

RECRUITING

Related Publications (22)

• Haack M, Simpson N, Sethna N, Kaur S, Mullington J. Sleep deficiency and chronic pain: potential underlying mechanisms and clinical implications. Neuropsychopharmacology. 2020 Jan;45(1):205-216. doi: 10.1038/s41386-019-0439-z. Epub 2019 Jun 17.

  PMID: 31207606 BACKGROUND

• Moore S, Stockbridge L. Fresnel prisms in the management of combined horizontal and vertical strabismus. Am Orthopt J. 1972;22:14-21. No abstract available.

  PMID: 5052847 BACKGROUND

• Nabavi SM, Nabavi SF, Sureda A, Xiao J, Dehpour AR, Shirooie S, Silva AS, Baldi A, Khan H, Daglia M. Anti-inflammatory effects of Melatonin: A mechanistic review. Crit Rev Food Sci Nutr. 2019;59(sup1):S4-S16. doi: 10.1080/10408398.2018.1487927. Epub 2019 Mar 21.

  PMID: 29902071 BACKGROUND

• Madsen BK, Zetner D, Moller AM, Rosenberg J. Melatonin for preoperative and postoperative anxiety in adults. Cochrane Database Syst Rev. 2020 Dec 8;12(12):CD009861. doi: 10.1002/14651858.CD009861.pub3.

  PMID: 33319916 BACKGROUND

• Yousaf F, Seet E, Venkatraghavan L, Abrishami A, Chung F. Efficacy and safety of melatonin as an anxiolytic and analgesic in the perioperative period: a qualitative systematic review of randomized trials. Anesthesiology. 2010 Oct;113(4):968-76. doi: 10.1097/ALN.0b013e3181e7d626.

  PMID: 20823763 BACKGROUND

• Andersen LP, Werner MU, Rosenberg J, Gogenur I. A systematic review of peri-operative melatonin. Anaesthesia. 2014 Oct;69(10):1163-71. doi: 10.1111/anae.12717. Epub 2014 May 19.

  PMID: 24835540 BACKGROUND

• Caumo W, Torres F, Moreira NL Jr, Auzani JA, Monteiro CA, Londero G, Ribeiro DF, Hidalgo MP. The clinical impact of preoperative melatonin on postoperative outcomes in patients undergoing abdominal hysterectomy. Anesth Analg. 2007 Nov;105(5):1263-71, table of contents. doi: 10.1213/01.ane.0000282834.78456.90.

  PMID: 17959953 BACKGROUND

• Caumo W, Levandovski R, Hidalgo MP. Preoperative anxiolytic effect of melatonin and clonidine on postoperative pain and morphine consumption in patients undergoing abdominal hysterectomy: a double-blind, randomized, placebo-controlled study. J Pain. 2009 Jan;10(1):100-8. doi: 10.1016/j.jpain.2008.08.007. Epub 2008 Nov 17.

  PMID: 19010741 BACKGROUND

• Barlow KM, Brooks BL, Esser MJ, Kirton A, Mikrogianakis A, Zemek RL, MacMaster FP, Nettel-Aguirre A, Yeates KO, Kirk V, Hutchison JS, Crawford S, Turley B, Cameron C, Hill MD, Samuel T, Buchhalter J, Richer L, Platt R, Boyd R, Dewey D. Efficacy of Melatonin in Children With Postconcussive Symptoms: A Randomized Clinical Trial. Pediatrics. 2020 Apr;145(4):e20192812. doi: 10.1542/peds.2019-2812. Epub 2020 Mar 26.

  PMID: 32217739 BACKGROUND

• Buscemi N, Vandermeer B, Hooton N, Pandya R, Tjosvold L, Hartling L, Baker G, Klassen TP, Vohra S. The efficacy and safety of exogenous melatonin for primary sleep disorders. A meta-analysis. J Gen Intern Med. 2005 Dec;20(12):1151-8. doi: 10.1111/j.1525-1497.2005.0243.x.

  PMID: 16423108 BACKGROUND

• Wei S, Smits MG, Tang X, Kuang L, Meng H, Ni S, Xiao M, Zhou X. Efficacy and safety of melatonin for sleep onset insomnia in children and adolescents: a meta-analysis of randomized controlled trials. Sleep Med. 2020 Apr;68:1-8. doi: 10.1016/j.sleep.2019.02.017. Epub 2019 Mar 9.

  PMID: 31982807 BACKGROUND

• Smits MG, van Stel HF, van der Heijden K, Meijer AM, Coenen AM, Kerkhof GA. Melatonin improves health status and sleep in children with idiopathic chronic sleep-onset insomnia: a randomized placebo-controlled trial. J Am Acad Child Adolesc Psychiatry. 2003 Nov;42(11):1286-93. doi: 10.1097/01.chi.0000085756.71002.86.

  PMID: 14566165 BACKGROUND

• Smits MG, Nagtegaal EE, van der Heijden J, Coenen AM, Kerkhof GA. Melatonin for chronic sleep onset insomnia in children: a randomized placebo-controlled trial. J Child Neurol. 2001 Feb;16(2):86-92. doi: 10.1177/088307380101600204.

  PMID: 11292231 BACKGROUND

• Karkela J, Vakkuri O, Kaukinen S, Huang WQ, Pasanen M. The influence of anaesthesia and surgery on the circadian rhythm of melatonin. Acta Anaesthesiol Scand. 2002 Jan;46(1):30-6. doi: 10.1034/j.1399-6576.2002.460106.x.

  PMID: 11903069 BACKGROUND

• Rabbitts JA, Groenewald CB, Tai GG, Palermo TM. Presurgical psychosocial predictors of acute postsurgical pain and quality of life in children undergoing major surgery. J Pain. 2015 Mar;16(3):226-34. doi: 10.1016/j.jpain.2014.11.015. Epub 2014 Dec 22.

  PMID: 25540939 BACKGROUND

• Groenewald CB, Beals-Erickson SE, Ralston-Wilson J, Rabbitts JA, Palermo TM. Complementary and Alternative Medicine Use by Children With Pain in the United States. Acad Pediatr. 2017 Sep-Oct;17(7):785-793. doi: 10.1016/j.acap.2017.02.008. Epub 2017 Feb 21.

  PMID: 28232257 BACKGROUND

• Rabbitts JA, Kain Z. Perioperative Care for Adolescents Undergoing Major Surgery: A Biopsychosocial Conceptual Framework. Anesth Analg. 2019 Oct;129(4):1181-1184. doi: 10.1213/ANE.0000000000004048. No abstract available.

  PMID: 30720491 BACKGROUND

• Rosenbloom BN, Rabbitts JA, Palermo TM. A developmental perspective on the impact of chronic pain in late adolescence and early adulthood: implications for assessment and intervention. Pain. 2017 Sep;158(9):1629-1632. doi: 10.1097/j.pain.0000000000000888. No abstract available.

  PMID: 28267063 BACKGROUND

• Rabbitts JA, Zhou C, Groenewald CB, Durkin L, Palermo TM. Trajectories of postsurgical pain in children: risk factors and impact of late pain recovery on long-term health outcomes after major surgery. Pain. 2015 Nov;156(11):2383-2389. doi: 10.1097/j.pain.0000000000000281.

  PMID: 26381701 BACKGROUND

• Rabbitts JA, Palermo TM, Zhou C, Mangione-Smith R. Pain and Health-Related Quality of Life After Pediatric Inpatient Surgery. J Pain. 2015 Dec;16(12):1334-1341. doi: 10.1016/j.jpain.2015.09.005. Epub 2015 Sep 28.

  PMID: 26416163 BACKGROUND

• Rabbitts JA, Zhou C, Narayanan A, Palermo TM. Longitudinal and Temporal Associations Between Daily Pain and Sleep Patterns After Major Pediatric Surgery. J Pain. 2017 Jun;18(6):656-663. doi: 10.1016/j.jpain.2017.01.004. Epub 2017 Jan 26.

  PMID: 28131699 BACKGROUND

• Wang Z, Li Y, Lin D, Ma J. Effect of Melatonin on Postoperative Pain and Perioperative Opioid Use: A Meta-analysis and Trial Sequential Analysis. Pain Pract. 2021 Feb;21(2):190-203. doi: 10.1111/papr.12948. Epub 2020 Oct 2.

  PMID: 32916009 BACKGROUND

MeSH Terms

Conditions

Scoliosis; Kyphosis; Spondylolisthesis; Acute Pain; Chronic Pain; Pain, Postoperative

Condition Hierarchy (Ancestors)

Spinal Curvatures; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Spondylolysis; Spondylosis; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Postoperative Complications; Pathologic Processes

Central Study Contacts

Jennifer A Rabbitts, M.B.Ch.B.

CONTACT

(650) 427-0187; surgerysmart@stanford.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Anesthesiology, Perioperative, and Pain Medicine

Study Record Dates

• First Submitted: October 9, 2023
• First Posted: October 23, 2023
• Study Start: May 30, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): March 31, 2028
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Shared data generated from this project will be available as soon as possible, and no later than the time of publication of the analyses examining the study's primary aims. The duration of preservation and sharing of the data will be a minimum of 10 years after the funding period.
• Access Criteria: Data will be made available in a data repository which allows research teams to restrict access to the data to qualified investigators with an appropriate research question and approved data use agreement. The data use agreement limits subsequent use to the terms of the approved request and requires that users maintain data security and refrain from any attempts to re-identify research participants or engage in any unauthorized use of the data. PI Dr. Jennifer Rabbitts, ORCID: https://orcid.org/0000-0003-4800-1080, will oversee day-to-day data management activities and data sharing. Dr. Rabbitts will also oversee broader issues of DMS (Data Management and Sharing) Plan compliance oversight reporting which will include maintaining databases, as part of general data stewardship, reporting, and compliance processes.

Locations

US (1)