Pilot Study of Sleep Therapy and Biomarkers in Children With Autism Spectrum Disorders

Stony Brook University

Status and phase: Terminated; Phase 2

Conditions: Autism Spectrum Disorder

Treatments: Drug: Melatonin and Donepezil; Other: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02487082

65708

Details and patient eligibility

About

The purpose of this study is to test the combined effect of melatonin and donepezil on improving sleep and behavior in children with Autism Spectrum Disorders. Melatonin is a natural neurohormone that helps regulate sleep and wake cycles. Donepezil is used to improve mental function for people with Alzheimer's disease. Children with Autism Spectrum Disorders are more likely to have problems sleeping than other children. This difficulty has been linked to daytime behavioral problems and family stress.

Full description

The goal of the present exploratory investigation is to see if there is a suggestion of a large additive or synergistic effect of melatonin and donepezil given together. Individually both medications improve sleep, but appear do so in different ways, with melatonin altering circadian rhythm and donepezil altering the characteristics of REM sleep. In this pilot investigation we will examine whether their combined effects on sleep lead to a large improvement in the behavior of children with ASD. Combined pharmacotherapy is very common in clinical practice, but is rarely studied in research (Comer et al. 2010). These two medications are both well tolerated and there is no negative drug interaction between the two. This investigation will use an RCT as well as a set of exploratory analyses to assess the combined effects of these two medications compared to placebo in terms of behavioral and sleep measures. In addition we will collect exploratory biomarkers (e.g., digit ratio, the ratio of the lengths different fingers as a measure of the balance of sex hormones during embryonic development) to relate to the various sleep and behavioral measures. A positive signal from this study may be used to guide a follow-up study with greater numbers of study subjects and statistical power.

Enrollment: 12 patients

Sex: All

Ages: 4 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Both male and female children
• Ages 4 to 17 1/2 years
• Diagnosis with Autism Spectrum Disorder on the basis of the clinical judgment of an autism specialist, preferably using the Autism Diagnostic Observation Schedule or the Autism Diagnostic Interview-Revised.

Exclusion criteria

• Abnormal electroencephalogram in the past month
• Cardiovascular problems
• Asthma
• Respiratory disease
• Peptic ulcer disease
• Renal or hepatic dysfunction (abnormal blood urea nitrogen/creatinine or 2 times elevated liver transaminases)
• Urinary tract obstruction
• Underweight (body mass index < 5th percentile compared to age and sex matched population)
• Other serious illness
• Use of any of the following drugs that might interact with study medications (anticholinergics, systemic corticosteroids, phenobarbital, peginterferon, beta-blockers or any drug that may cause arrhythmias). Drugs that induce or inhibit cytochrome P450 2D6 and cytochrome P450 3A4 (enzymes important for drug metabolism) will be allowed because any effects of such medications are likely to be lost in individual variability due to genetic polymorphisms.
• Use of medications affecting sleep with a half-life of 7 days or more. [Children on medications affecting sleep with a half-life of less than 7 days (including melatonin and donepezil) are eligible if they agree to discontinue use for the duration of the trial.]
• Pregnancy and lactation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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12 participants in 2 patient groups

Group A

Other group

Description:

Run-In Phase: Placebo. Phase 1 \& Phase 2: Melatonin and donepezil (melatonin 3mg and donepezil 1.25-5mg based on age/weight each night) for 10 weeks Wash-Out Phase: no active or placebo medication. Note: Dosage of study drug varies with age/weight. Younger children (\<12 years or \< 80 lbs. weight start at a lower dose of donepezil (1.25 mg/night) and increase to 2.5 mg/night after one week. Older children (\>= 12 years or \>= 80 lbs weight) start at 3 mg donepezil and increase to 5 mg after one week. The dose of melatonin remains stable at 3 mg throughout for both groups.

Treatment:

Other: Placebo

Drug: Melatonin and Donepezil

Group B

Other group

Description:

Run-In Phase: Placebo. Phase 1: Placebo. Phase 2: Melatonin and donepezil (melatonin 3mg and donepezil 1.25-5mg based on age/weight each night) or placebo for 5 weeks Wash-out Phase: no active or placebo medication. Note: Dosage of study drug varies with age/weight. Younger children (\<12 years or \< 80 lbs. weight start at a lower dose of donepezil (1.25 mg/night) and increase to 2.5 mg/night after one week. Older children (\>= 12 years or \>= 80 lbs weight) start at 3 mg donepezil and increase to 5 mg after one week. The dose of melatonin remains stable at 3 mg throughout for both groups.

Treatment:

Other: Placebo

Drug: Melatonin and Donepezil