melatonin intervention for neurocognitive deficits in the st. jude lifetime cohort

Conditions: Cancer Malignancies

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.

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.

Eligibility criteria:
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

Keywords: melatonin neurocognitive impairment sleep disturbance childhood cancer survivors