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

NCT04932096 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: GPEDI1282A1K23HL150229-01A1
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Traumatic Brain Injury; Critical Illness; Sleep

Keywords

pediatric; traumatic brain injury; melatonin; sleep; intervention

Outcome Measures

Primary Outcomes (3)

• Sleep Disturbances Scale for Children

  Sleep Disturbances Scale for Children (SDSC): 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. Raw scores are converted to measure defined T-scores (mean=50, SD=10) for the total score and 6 subscale scores with higher scores indicating worse dysfunction, and T-scores greater than 60 generally indicating clinically significant dysfunction in the total score and all 6 subscale scores. The subscales include Initiation and Maintenance, Arousal, Breathing, Transition, Somnolence, and Hyperhidrosis.

  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 30 days

Secondary Outcomes (13)

• Adherence Quantitative

  1-month

• Adherence Qualitative

  1-month

• Pediatric Quality of Life Inventory Multidimensional Fatigue Scale

  1-month

• Chronotype

  1-month

• Sleep Latency

  1-month

Other Outcomes (7)

• Reason for Non-adherence

  1-month

• Health Related Quality of Life

  1-month

• Cognitive Functioning

  1-month

Study Arms (2)

Melatonin

EXPERIMENTAL

(melatonin doses of 3mg or 5mg based on patient size given nightly 1 hour prior to bedtime every night for 30 days)

Drug: melatonin

Placebo

PLACEBO COMPARATOR

Placebo

Other: placebo

Interventions

melatonin DRUG

melatonin supplementation

Melatonin

placebo OTHER

microcrystalline cellulose filled capsule

Placebo

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Oregon Health and Science University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Related Publications (3)

• 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.

  PMID: 32328648 BACKGROUND

• 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.

  PMID: 31797275 BACKGROUND

• 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.

  PMID: 31735567 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Brain Injuries, Traumatic; Critical Illness

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Pilot trial with small number of participants recruited. Results focus on feasibility, was not powered to detect differences in sleep and other secondary outcomes.

Results Point of Contact

• Title: Dr. Cydni Williams
• Organization: Oregon Health & Science University

willicyd@ohsu.edu

5034945522

Study Officials

• Cydni Williams, MD

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 2, 2021
• First Posted: June 18, 2021
• Study Start: January 2, 2023
• Primary Completion: March 1, 2025
• Study Completion: March 1, 2025
• Last Updated: August 20, 2025
• Results First Posted: August 20, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• 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.
• Access Criteria: Requests for data can be made by contacting the Principal Investigator

Locations

US (1)