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

• ClinicalTrials.gov Identifier: NCT01700959
• Recruitment Status: Completed
• First Posted: October 4, 2012
• Results First Posted: June 28, 2018
• Last Update Posted: June 28, 2018
• Sponsor: St. Jude Children's Research Hospital
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): St. Jude Children's Research Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cancer Malignancies	Drug: melatonin; Drug: placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 911 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Melatonin Intervention For Neurocognitive Deficits in the St. Jude Lifetime Cohort
• Actual Study Start Date: February 6, 2013
• Actual Primary Completion Date: April 19, 2017
• Actual Study Completion Date: April 19, 2017

Arms and Interventions

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 Name: 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.

Outcome Measures

Primary Outcome Measures :

1. Neurocognitive Function as Measured by Performance on Standardized Tests of Attention, Memory, and Executive Function. [ Time Frame: 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 :

1. Sleep Onset Latency as Measured by Actigraphy and Self-report. [ Time Frame: 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.
2. 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. [ Time Frame: 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.

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, Tennessee

St. Jude Children's Research Hospital

Memphis, Tennessee, United States, 38105

Sponsors and Collaborators

St. Jude Children's Research Hospital

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Tara Brinkman, PhD; St. Jude Children's Research Hospital

  Study Documents (Full-Text)

Documents provided by St. Jude Children's Research Hospital:

Study Protocol and Statistical Analysis Plan  [PDF] October 11, 2016

More Information

Additional Information:

St. Jude Children's Research Hospital 

Clinical Trials Open at St. Jude 

• Responsible Party: St. Jude Children's Research Hospital
• ClinicalTrials.gov Identifier: NCT01700959
• Other Study ID Numbers: MIND; P30CA021765 ( U.S. NIH Grant/Contract ); NCI-2012-02053 ( Registry Identifier: NCI Clinical Trial Registration Program )
• First Posted: October 4, 2012
• Results First Posted: June 28, 2018
• Last Update Posted: June 28, 2018
• Last Verified: March 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by St. Jude Children's Research Hospital:

Melatonin; Neurocognitive impairment; Sleep disturbance; Childhood cancer survivors

Additional relevant MeSH terms:

Neoplasms; Melatonin; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Central Nervous System Depressants