Chromosome Disorders
Conditions
Keywords
Smith-Magenis Syndrome, melatonin, circadian rhythm, sleep
Brief summary
The goal of this pilot project is to determine whether melatonin levels are disordered in patients with Smith-Magenis Syndrome (SMS) and whether melatonin treatment can correct abnormal circadian rhythms in SMS patients. In addition, the study investigates the effects of bright light in an elderly control population that exhibits low melatonin secretion.
Detailed description
Participation involves 5 stages for SMS patients. First, Subjects will complete 4 sessions of 25-hour salivary or plasma sampling, with the last sampling occurring in front of a bright light box. Second, subjects will enroll in the melatonin treatment phase, involving a daily dose (up to 3 mg) for up to one year, with frequent (every 2-4 weeks) of 25-hour salivary or plasma sampling. During this stage, the subject and/or caregiver may also be asked to wear an activity wrist monitor, complete a daily sleep diary and behavioral questionnaires. Third, the subject may be asked to complete up to 3 25-hour sampling periods and take a melatonin pill on the same day to test how their body metabolizes the hormone, melatonin. The fourth stage is for subjects who are found to have an abnormal body rhythm. Subjects will complete a 25-hour plasma sampling period under bedrest to test for a hormone, Cortisol. The fifth stage is an optional 12-hour sleep analysis (polysomnography) to test for sleep disorders. Control participants will complete an abbreviated protocol of the 3 baseline 25-hour sampling periods and 1 involving bright light exposure.
Interventions
DIETARY_SUPPLEMENTMelatonin
up to 3 mg, daily, for up to 1 year
DEVICEEnviro-light artificial light box
Subjects will sit in front of an artificial, fluorescent light box (10,000 lux) while completing 25-hours of hourly plasma samples. The light lux level will be well below that identified as safe by the FDA.
Sponsors
Oregon Health and Science University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
3 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Control participants: * 30 individuals: ages 55-85, * healthy without significant active medical problems. * SMS patients: * 20 individuals: ages 3-50, * with a clinical diagnosis of Smith-Magenis Syndrome by a qualified Medical Geneticist, confirmed by cytogenetic analysis documenting deletion of chromosome band 17p11.2.
Exclusion criteria
* Control participants: * A current Axis I psychiatric or substance abuse disorder according to the DSM-IV Manual, abnormal heart, liver or kidney function, diagnoses of neurodegenerative or cerebrovascular disease (Alzheimer's disease, Parkinson's disease, stroke, etc.), * cognitive impairment (Mini-Mental State Score \< 23) but without a formal diagnosis of dementia, * active symptoms of depression (Geriatric Depression Scale: 30 pt. version \> 10), * current diagnosis of cataracts, * macular degeneration or retinopathy based on eye exam by an optometrist or ophthalmologist within the past year.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Circadian Phase Marker, as Measured by the Melatonin Levels in Serial Salivary and/or Plasma Samples | every 2-4 weeks throughout the entire study |
Secondary
| Measure | Time frame |
|---|---|
| Polysomnography Sleep Disorder Assessment | 1 optional, 12-hour assessment towards the end of the study |
| Wrist Actigraph Activity Levels as a Secondary Indicator of Circadian Phase | every 2-4 weeks throughout the entire study along with every Circadian Phase Marker assessment |
Countries
United States
Participant flow
Pre-assignment details
The PI has retired from the institution. Sincere efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available.
Participants by arm
| Arm | Count |
|---|---|
| Light Box Subjects will sit in front of a fluorescent bright light box while completing plasma samples to test for melatonin suppression in blood. This will be completed by both the SMS patient group and the control group of elderly individuals.
Enviro-light artificial light box: Subjects will sit in front of an artificial, fluorescent light box (10,000 lux) while completing 25-hours of hourly plasma samples. The light lux level will be well below that identified as safe by the FDA. | 0 |
| Melatonin Subjects will take up to 3 mg of melatonin daily and will complete frequent (every 2-4 weeks) of saliva and/or plasma sampling to test for a change in the timing of the body clock in response to the melatonin.
Melatonin: up to 3 mg, daily, for up to 1 year | 0 |
| Total | 0 |
Baseline characteristics
| Characteristic | — |
|---|---|
| Region of Enrollment United States | — participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Circadian Phase Marker, as Measured by the Melatonin Levels in Serial Salivary and/or Plasma Samples
Time frame: every 2-4 weeks throughout the entire study
Population: The PI has retired from the institution. Sincere efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available.
Secondary
Polysomnography Sleep Disorder Assessment
Time frame: 1 optional, 12-hour assessment towards the end of the study
Population: The PI has retired from the institution. Sincere efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available.
Secondary
Wrist Actigraph Activity Levels as a Secondary Indicator of Circadian Phase
Time frame: every 2-4 weeks throughout the entire study along with every Circadian Phase Marker assessment
Population: The PI has retired from the institution. Sincere efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available.