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

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.

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.

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