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

Phase 3

Completed

Conditions: Cancer Malignancies

Interventions: Drug: melatonin
Drug: placebo

Registration Number: NCT01700959

Lead Sponsor: St. Jude Children's Research Hospital

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 911

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Melatonin	melatonin	Participants receive 3 mgs of time-release melatonin 1-2 hours prior to bedtime.
Placebo	placebo	Participants receive a placebo identical to the time-release melatonin and are instructed to take it 1-2 hours prior to bedtime.

Primary Outcome Measures

Name	Time	Method
Neurocognitive Function as Measured by Performance on Standardized Tests of Attention, Memory, and Executive Function.	Baseline and 6 months after start of therapy	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.

Secondary Outcome Measures

Name	Time	Method
Sleep Onset Latency as Measured by Actigraphy and Self-report.	Baseline and six months after start of therapy	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.
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.	Baseline and six months after start of therapy	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.