Melatonin Intervention For Neurocognitive Deficits in the St. Jude Lifetime Cohort

Primary objective:

1. To examine the efficacy of melatonin treatment on neurocognitive functioning in adult survivors of childhood cancer.

Secondary objectives:

1. To evaluate the efficacy of melatonin treatment on delayed sleep onset latency in long-term childhood cancer survivors.
2. To investigate whether improvement in sleep onset latency due to melatonin treatment is associated with neurocognitive improvement in long-term childhood cancer survivors.

This study is a randomized double-blind placebo controlled trial of time release melatonin for adult survivors of childhood cancer who demonstrate impaired neurocognitive functioning and/or difficulty falling asleep.

Study Overview

• Status: Completed
• Conditions: Cancer Malignancies
• Intervention / Treatment: Drug: melatonin; Drug: placebo

Detailed Description

All participants undergo a general neurocognitive evaluation at baseline and 6-month follow-up, focused on assessment of intelligence, academic skills, attention, processing speed, memory and executive functions.

Sleep parameters using self-report and actigraphy will be assessed at three time points during the study: Baseline, 3-months, and 6-months.

Participants will be divided into 3 mutually exclusive groups:

• Cohort 1: Participant has neurocognitive impairment defined as performance on at least one measure of attention, memory, and/or executive functioning at or below the 10th percentile, AND is absent of delayed sleep onset latency defined as an inability to fall asleep within 30 minutes less than once a week during the past month.
• Cohort 2: Participant has neurocognitive impairment defined as performance on at least one measure of attention, memory, and/or executive functioning at or below the 10th percentile, AND has delayed sleep onset latency defined as self-report of an inability to fall asleep within 30 minutes at least once a week during the past month.
• Cohort 3: Participant is absent of neurocognitive impairment defined as performance >10th percentile on all six measures of attention, memory, and executive functioning, AND has delayed sleep onset latency defined as self-report of an inability to fall asleep within 30 minutes > once a week during the past month.

Within each group, participants will be randomly assigned to take either 3 mgs of time release melatonin or placebo 1-2 hours before bedtime each night for 6 months.

Psychosocial measures of health-related quality of life and psychological distress will be completed at baseline and following 6 months of melatonin/placebo treatment.

Biological samples for serum melatonin levels will be collected at baseline and at the 6 month follow-up evaluation.

• Study Type: Interventional
• Enrollment (Actual): 911
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A St. Jude Life participant who was previously treated at St. Jude Children's Research Hospital
• 10 or more years from diagnosis
• 18 years of age or older
• Able to speak and understand the English language
• Participant has a full scale intelligence quotient (FSIQ) score >79.

• Cohort 1 participant:

  • Has neurocognitive impairment defined as performance on at least one measure of attention, memory, and/or executive functioning ≤10th percentile.
  • Is absent of delayed sleep onset latency defined as an inability to fall asleep within 30 minutes < once a week during the past month.

• Cohort 2 participant:

  • Has neurocognitive impairment defined as performance on at least one measure of attention, memory, and/or executive functioning ≤10th percentile.
  • Has delayed sleep onset latency defined as self-report of an inability to fall asleep within 30 minutes ≥ once a week during the past month.

• Cohort 3 participant:

  • Is absent of neurocognitive impairment defined as performance >10th percentile on all six measures of attention, memory, and executive functioning.
  • Has delayed sleep onset latency defined as self-report of an inability to fall asleep within 30 minutes ≥ once a week during the past month.
• Female participant of childbearing age must not be pregnant or lactating
• Female research participant of childbearing age and male research participant of child fathering potential agrees to use safe contraceptive methods

Exclusion Criteria:

• Known allergy to melatonin or any ingredients of the study product or placebo
• Participant currently is taking melatonin
• Known sleep apnea or medically treated sleep disorder (e.g. restless leg syndrome)
• Known diabetes mellitus - insulin treated
• Participant has uncontrolled seizure disorder in past 12 months
• Reported current illicit drug or alcohol abuse or dependence
• Reported current major psychiatric illness (i.e. schizophrenia, bipolar disorder)
• Current treatment with: (1) benzodiazepines or other central nervous system depressants, (2) fluvoxamine, (3) anticoagulants (e.g. coumadin), (4) immunosuppressant or corticosteroids, OR (5) nifedipine (Procardia XL(R))
• Employed in a position that requires night work (i.e. 10pm to 6am)
• Females who are pregnant or lactating/nursing
• History of neurologic event (i.e. traumatic brain injury) unrelated to cancer or its treatment
• Sensory impairment (vision, hearing) that prohibits completion of neurocognitive examination

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Melatonin; Participants receive 3 mgs of time-release melatonin 1-2 hours prior to bedtime.	Drug: melatonin; Melatonin 3mg time release will be given. Participants will be instructed to take one 3mg time released tablet by mouth approximately 1-2 hours before initiating sleep onset, preferably at the same time each night.; Other Names: N-Acetyl-5-Methoxytryptamine
Placebo Comparator: Placebo; Participants receive a placebo identical to the time-release melatonin and are instructed to take it 1-2 hours prior to bedtime.	Drug: placebo; Placebo tablets to match the melatonin will be comprised of inert substances.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurocognitive Function as Measured by Performance on Standardized Tests of Attention, Memory, and Executive Function.	Efficacy of melatonin treatment on neurocognitive functioning in adult survivors of childhood cancer (Cohorts 1 and 2 only). The measures were analyzed to compare change in neurocognitive performance from baseline to 6 months between active treatment and placebo groups. The unit of measure is a standardized z-score with a mean of 0 and standard deviation of 1. A higher z-score represents a better outcome.	Baseline and 6 months after start of therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep Onset Latency as Measured by Actigraphy and Self-report.	Efficacy of melatonin on delayed sleep onset latency in long-term childhood cancer survivors (Cohorts 2 and 3 only). The measures were analyzed to compare change in sleep onset latency from baseline to 6 months between active treatment and placebo groups.	Baseline and six months after start of therapy
Neurocognitive Function as Measured by Performance on Standardized Tests of Attention, Memory, and Executive Function, and Sleep Onset Latency as Measured by Actigraphy and Self-report.	Investigate whether improvement in sleep onset latency due to melatonin treatment is associated with neurocognitive improvement in long-term childhood cancer survivors (Cohort 2). The change in neurocognitive performance from baseline to 6 months will be examined in relation to change in sleep onset latency. The unit of measure is a standardized z-score with a mean of 0 and standard deviation of 1. The unit of measurement is a correlation coefficient (Pearson's R2). The range is from -1.0 to 1.0. A zero indicates no correlation while values closer to -1.0 or 1.0 reflect a stronger association. A negative correlation suggests that as sleep latency decreased, neurocognitive functioning improved.	Baseline and six months after start of therapy

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Tara Brinkman, Phd, St. Jude Children's Research Hospital

Publications and helpful links

Helpful Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2013
• Primary Completion (Actual): April 19, 2017
• Study Completion (Actual): April 19, 2017

Study Registration Dates

• First Submitted: September 25, 2012
• First Submitted That Met QC Criteria: October 2, 2012
• First Posted (Estimate): October 4, 2012

Study Record Updates

• Last Update Posted (Actual): June 28, 2018
• Last Update Submitted That Met QC Criteria: June 26, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Melatonin; Sleep disturbance; Childhood cancer survivors; Neurocognitive impairment
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: MIND; P30CA021765 (U.S. NIH Grant/Contract); NCI-2012-02053 (Registry Identifier: NCI Clinical Trial Registration Program)

Drug and device information, study documents

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