Studying Melatonin and Recovery in Teens

Spondylolisthesis Clinical Trial

— SurgerySMART  

Official title:

SurgerySMART: Studying Melatonin and Recovery in Teens

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06093477
• Other study ID #: IRB-71745
• Secondary ID: 7K24AR080786-02
• Status: Recruiting
• Phase: N/A
• Start date: May 30, 2024
• Est. completion date: June 2028

Study information

• Verified date: June 2024
• Source: Stanford University
• Contact: Jennifer A Rabbitts, M.B.Ch.B.
• Phone: (650) 427-0187
• Email: surgerysmart[@]stanford.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The investigators will enroll a total of 45 adolescents ages 12-18 years old who are scheduled to undergo major musculoskeletal surgery and one of their caregivers who meet inclusion and exclusion criteria. Participants will be asked to:

1. Take melatonin or a placebo before and after surgery. All participants will receive sleep hygiene instructions.

2. Wear a watch-like actigraphy device before and after surgery

3. Complete 1-minute check-in surveys twice each day, for about 5 weeks total before and after surgery

4. Complete 10-20-minute online surveys 3 times over 4 months.

Researchers will compare participants randomized to the placebo arm and melatonin arm to see if the trial design and outcomes are both feasible and acceptable to patients and their families.

The main aims are:

Aim 1. To assess the feasibility and acceptability of melatonin for youth undergoing musculoskeletal surgery Aim 2. To determine optimal primary and secondary outcomes (sleep, pain, health-related quality of life) at short-term (during the initial 21 days) and at final follow-up (3 months after surgery). The investigators will examine completion rates, the extent and pattern of missing data, and gather data to provide effect estimates, variances, and 95% confidence intervals.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: June 2028
• Est. primary completion date: March 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 18 Years

Eligibility

Inclusion Criteria:

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

Parents/caregivers

• Biological parent or legal guardian of youth

• Can read and understand English

Exclusion Criteria:

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

Related Conditions & MeSH terms

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

Intervention

Dietary Supplement:
• Fast-Dissolve Melatonin Pill
Participants in this arm will take 3mg of melatonin in fast-dissolve pill form daily during the specified study period.

Other:
• Fast-Dissolve Placebo Pill
Participants in this arm will take 3mg of placebo in fast-dissolve pill form daily during the specified study period.

Locations

Country	Name	City	State
United States	Lucile Packard Children's Hospital	Palo Alto	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Country where clinical trial is conducted

United States, 

References & Publications (22)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse Events	Youth and parents will be asked open-ended questions about adverse events.	Treatment phase of 14 days before surgery through 21 days post-op (T2) and 7 days at 3-month follow-up (T3)
Other	Concomitant therapy	Youth and parents will be asked open-ended questions about concomitant therapies the patient may have taken (use of sleep aids).	Assessed one time at 21 days post-op (T2) and one time at 3-month follow-up (T3)
Other	Pediatric Anxiety	Youth will complete the PROMIS Anxiety Short Form 8a, which assesses the pure domain of anxiety in children and adolescents (8 items) in the prior 7 days, with response options indicated on a 5-point scale. Higher scores indicate greater severity of anxiety. Response options range from 1 (Never) to 5 (Almost Always). Raw scores for anxiety and depression are obtained by summing the corresponding items' response values, and range from 8 to 40 with higher scores indicating higher distress.	Assessed one time on day before surgery (T2)
Primary	Treatment Adherence	Youth will self-report daily medication administration on the evening diary, 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)
Primary	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 Dav 21 post-op, and day before surgery (T2)
Primary	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)
Primary	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 Dav 21 post-op, and day before surgery (T2)
Secondary	Change in Sleep Quality	Youth will complete the Adolescent Sleep Wake Scale (ASWS), a 10-item measure of sleep quality over the past month rated on a 6-point Likert scale ranging from "Always" to "Never". The measure assesses five behavioral dimensions of sleep quality: (1) going to bed, (2) falling asleep/latency, (3) maintaining sleep, (4) re-initiating sleep, and (5) returning to wakefulness, and yields a total sleep quality score.	Pre-treatment (T1) and one time at 3-month follow-up (T3)
Secondary	Change in Peri-operative Sleep Quality	Youth will complete once daily online diaries assessing daily sleep quality in the morning. Sleep quality will be rated on an 11-point scale ranging from 0 (Extremely poor sleep) to 10 (Extremely good sleep). A higher score indicates higher quality sleep.	Treatment phase of 14 days before surgery through 21 days post-op (T2) and 7 days at 3-month follow-up (T3)
Secondary	Change in Sleep Duration	Youth will wear an actigraphy monitor to measure sleep duration. Youth will also report on sleep and wake times on the online morning diary, which will be used to assist with actigraphy scoring. Actigraphic sleep variables will include: minutes of estimated sleep, and sleep efficiency.	Treatment phase of 14 days before surgery through 21 days post-op (T2) and 7 days at 3-month follow-up (T3)
Secondary	Change in Health-related Quality of Life	Youth will complete the Pediatric Quality of Life Inventory (PedsQL), a 15-item measure that assesses self-reported physical, social, and emotional health-related qualify of life over the prior 7 days. The measure yields Physical Health, Psychosocial Health, and Total Health summary scores. The PedsQL is widely used and demonstrates good reliability for both the parent and child self-report measures. Scale scores range from 0 to 100. Higher scores indicate fewer difficulties (better) health-related quality of life.	Pre-treatment (T1) and one time at 3-month follow-up (T3)
Secondary	Change in Global Pain Severity	Youth will complete the Global Impression of Severity, a single item measure that assesses self-reported patient global impression of pain severity in the preceding 7 days. Response options range from 0 (none) to 3 (severe) with higher scores indicating higher pain severity.	Pre-treatment (T1), one time at Day 21 post-op (T2), and one time at 3-month follow-up (T3)
Secondary	Change in Pain Intensity and Interference	Youth will complete the Brief Pain Inventory (BPI), which assesses worst, least, average, and current pain intensity (4 items) and pain interference on daily functions (7 items) in the prior 7 days, with response options indicated on 11-point NRS. Items are averaged to yield scale scores, ranging from 0 to 10, with higher scores indicating greater pain intensity or interference.	Baseline pre-surgery assessment (T1), treatment phase of 14 days before surgery through 21 days after surgery (T2), and 7 days at 3-month follow-up (T3)