Sleep Management And Recovery After Traumatic Brain Injury in Kids: Pilot Intervention of Melatonin (SMARTKids)

Sleep Management And Recovery After Traumatic Brain Injury in Kids (SMARTKids): Evidence for Targeting Sleep to Improve Outcomes

Sleep wake disturbances compound recovery in over half of pediatric traumatic brain injury survivors, leading to impaired quality of life, and few effective interventions exist to treat this important morbidity. Therefore, this study will conduct a randomized controlled trial evaluating a melatonin intervention started during hospitalization and continued after discharge compared to placebo. The trial will investigate if this intervention is feasible, acceptable, and effective at reducing sleep wake disturbances as measured on the Sleep Disturbances Scale for Children 1-month after hospital discharge.

Participants will be randomly assigned to receive the intervention (melatonin) or to the control group (placebo) with a goal of equal numbers of participants in each group and all will receive sleep education. Participants will be followed closely after consent and outcomes will be assessed at hospital discharge, and 1-month. Outcomes will focus on feasibility (ability to recruit patients into the trial) and acceptability (patient safety and satisfaction), but will also assess the effectiveness of the intervention to reduce sleep disturbances after discharge. The investigators will assess sleep using questionnaires and actigraphy (watch-like activity monitors). Exploratory outcomes will include global health outcomes.

Study Overview

• Status: Recruiting
• Conditions: Critical Illness; Sleep; Traumatic Brain Injury
• Intervention / Treatment: Drug: melatonin; Other: placebo

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Cydni N Williams, MD; Phone Number: 503-494-5522; Email: willicyd@ohsu.edu
• Study Contact Backup: Name: Andrea Rano, BS; Phone Number: 503-494-5522; Email: rano@ohsu.edu

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
      • Contact: Andrea Rano, BS; Phone Number: 503-494-5522; Email: rano@ohsu.edu
      • Contact: Cydni Williams, MD; Phone Number: 503-494-5522; Email: willicyd@ohsu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion:

• Children age ≥6 years and <19 years
• Traumatic brain injury defined as disruption of the normal function of the brain resulting from blunt force injury with a severity defined as mild complicated, moderate, or severe by the Glasgow Coma Scale with the presence of intracranial injury on imaging
• Admission to Oregon Health & Science University Hospitals
• Deemed likely to survive hospitalization by clinical care team
• Able to tolerate enteral medications within 72 hours of admission
• Child participant resides with parent or legal guardian

Exclusion:

• Lack stable means of communication with study team (phone, email, mailing address)
• Abusive trauma suspected or confirmed
• Dialysis
• Extracorporeal support (e.g. ECMO)
• Significant liver injury defined as >2x normal levels for AST or ALT
• Clinical team safety concerns with use of intervention
• Pregnancy
• Prisoners

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: placebo; microcrystalline cellulose filled capsule
Experimental: Melatonin; (melatonin doses of 3mg or 5mg based on patient size given nightly 1 hour prior to bedtime every night for 30 days)	Drug: melatonin; melatonin supplementation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
sleep disturbance	Sleep Disturbances Scale for Children: 26-item parent proxy sleep questionnaire with higher scores reflecting greater disturbance and risk for clinically important sleep disorders. Each question is scored 1 through 5 for a range of possible total scores of 26 - 130.	1-month
Recruitment	Quantitative number of patients consented per patients approached	through study completion, an average of 6-months
Retention	Quantitative number of participants completing trial procedures per patients consented	through study completion, an average of 6-months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adherence quantitative	pill counts	1-month
adherence qualitative	participant report of compliance with treatment regimen evaluated by survey question estimating percentage of study days compliant with intervention	1-month
Fatigue	Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL MFS); 18 item parent proxy report of fatigue. Scores range 0-100 with higher scores indicating better function and less fatigue.	1-month
Chronotype	Children's Chronotype Questionnaire, parent reported survey of circadian rhythm characteristics. Each item assessed independently.	1-month
sleep latency	actigraphy measured time in minutes to fall asleep	1-month
total sleep time	actigraphy measured total time asleep in minutes	1-month
wake after sleep onset	actigraphy measured time in minutes awake after sleep onset	1-month
number of night awakenings	actigraphy measured number of instances awoken after sleep onset	1-month
sleep efficiency	actigraphy measure percentage of nighttime period spent asleep	1-month
sleep onset	time of day fell asleep	1-month
sleep offset	time of day waking from nighttime sleep	1-month
adverse events time 0	Evaluation of adverse events asking participants to report any side effects of study interventions	hospital discharge assessed up to 7 days
adverse events time 1	Evaluation of adverse events asking participants to report any side effects of study interventions	1-month

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
reason for non-adherence	qualitative response to survey question about reasons for non-compliance with treatment regimen or sleep plan	1-month
health related quality of life	Pediatric Quality of Life Inventory (PedsQL): parent reported measure of quality of life. Scores range 0-100 with higher scores indicating better quality of life.	1-month
cognitive functioning	Behavior Rating Inventory of Executive Function, second edition (BRIEF-2); parent proxy report of everyday executive function, reported as standardized Global Executive Composite T-score, with higher scores indicating worse function. T-scores range from 0-100, with a mean of 50 and standard deviation of 10.	1-month
physical functioning	Functional Status Scale, range 6-30, with higher scores indicating worse function	1-month
anxiety	Patient Reported Outcome Measurement Information System (PROMIS) anxiety short form T-score with higher scores indicating worse outcome. T-scores range from 0 - 100, with a mean of 50 and standard deviation of 10.	1-month
depression	Patient Reported Outcome Measurement Information System (PROMIS) depression short form T-score with higher scores indicating worse outcome. T-scores range from 0-100, with a mean of 50 and standard deviation of 10.	1-month
pain	Patient Reported Outcome Measurement Information System (PROMIS) pain intensity (raw score out of 10), and pain behavior (T-score with mean of 50 and standard deviation of 10) parent report forms; Higher scores indicate worse pain outcomes	1-month

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Cydni Williams, MD, Oregon Health and Science University

Publications and helpful links

General Publications

• Luther M, Poppert Cordts KM, Williams CN. Sleep disturbances after pediatric traumatic brain injury: a systematic review of prevalence, risk factors, and association with recovery. Sleep. 2020 Oct 13;43(10):zsaa083. doi: 10.1093/sleep/zsaa083.
• Poppert Cordts KM, Hall TA, Hartman ME, Luther M, Wagner A, Piantino J, Guilliams KP, Guerriero RM, Jara J, Williams CN. Sleep Measure Validation in a Pediatric Neurocritical Care Acquired Brain Injury Population. Neurocrit Care. 2020 Aug;33(1):196-206. doi: 10.1007/s12028-019-00883-5.
• Williams CN, Hartman ME, McEvoy CT, Hall TA, Lim MM, Shea SA, Luther M, Guilliams KP, Guerriero RM, Bosworth CC, Piantino JA. Sleep-Wake Disturbances After Acquired Brain Injury in Children Surviving Critical Care. Pediatr Neurol. 2020 Feb;103:43-51. doi: 10.1016/j.pediatrneurol.2019.08.010. Epub 2019 Aug 26.

Helpful Links

• Principal Investigator program website that will be updated regularly for PI contact information and study related materials

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2023
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): August 31, 2025

Study Registration Dates

• First Submitted: June 2, 2021
• First Submitted That Met QC Criteria: June 17, 2021
• First Posted (Actual): June 18, 2021

Study Record Updates

• Last Update Posted (Estimated): November 17, 2023
• Last Update Submitted That Met QC Criteria: November 14, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: sleep; melatonin; pediatric; intervention; traumatic brain injury
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease Attributes; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Critical Illness; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: GPEDI1282A; 1K23HL150229-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Basic tabular results will be entered into clinicaltrials.gov within 1 year of primary completion of the study. We will make participant data available to researchers once thoroughly de-identified and approved by our institutional review board within 1 year of study completion. Data will be made available on requests made directly to the Principal Investigator.
• IPD Sharing Time Frame: The study protocol and SAP will be shared upon approval by the Institutional Review Board, and the final approved study protocol and SAP with documentation of any amendments will be available at study completion. The ICF will be shared no later than 60days from enrollment of the last study visit. A CSR and analytic code for the primary outcomes analysis will be made available within 1 year of study completion.
• IPD Sharing Access Criteria: Requests for data can be made by contacting the Principal Investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No