Amyloid-beta
Conditions
Brief summary
The purpose of this study is to change the concentration of amyloid-beta in human cerebrospinal fluid (CSF) through modulation of the sleep-wake cycle.
Detailed description
The purpose of this research study is to investigate whether or not increasing or decreasing duration of sleep over one night will change the concentration of amyloid-beta in cerebral spinal fluid (CSF).
Interventions
DRUGSodium Oxybate
Sodium oxybate h.s.
BEHAVIORALSleep deprivation
36hr sleep deprivation
Sponsors
Washington University School of Medicine
National Institutes of Health (NIH)
National Institute on Aging (NIA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* cognitively normal or CDR 0 * negative for amyloid deposition by PET Pittsburgh Compound-B (PIB) imaging or CSF amyloid-beta-42 concentration * Age 18-60 * Average reported sleep time 6-10hrs
Exclusion criteria
* diagnosis of a sleep disorder such as sleep apnea, narcolepsy, or restless leg syndrome * positive ambulatory sleep study for obstructive sleep apnea (AHI \> 5 respiratory events per hour) that will be performed as part of initial screening prior to enrollment * Clinical Dementia Rating (CDR) \> 0 * tremor or other neurologic injury in the non-dominant upper extremity (such as stroke or tremor) that would prevent the use of actigraphy * current sleep walking or other sleep parasomnia * diagnosis and treatment of stroke, myocardial infarction or heart attack, * coronary artery disease, atrial fibrillation, or congestive heart failure * diagnosis and treatment of asthma or Chronic Obstructive Pulmonary Disease (COPD) * diagnosis and treatment of bipolar disorder, major depression, or Schizophrenia * current urinary or fecal incontinence * currently on a low salt diet * diagnosis and treatment of a neurologic disorder such as Parkinson's disease, epilepsy, multiple sclerosis * currently taking any blood thinner medications such as warfarin, Plavix, or Aspirin * kidney disease resulting in renal impairment * liver disease resulting in hepatic dysfunction * Pregnancy * currently taking sedating medications such as benzodiazepines * alcohol use at bedtime * tobacco use * BMI \>40 * contraindication to lumbar puncture * diabetes * sleep schedule outside the range of bedtime: 8pm-12am and waketime 4am-8am * self reported difficulty sleeping in an unfamiliar environment * use of sedative-hypnotic medications * inability to get in and out of bed * history or presence of any clinically significant medical condition, behavioral or psychiatric disorder, or surgical history based on medical record or patient report * history of drug abuse within the past 6 months * positive score on 2 or more categories on the Berlin questionnaire * participation in another investigational medicinal product or investigational device within the last 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Increase From Mean Baseline (07:00 to 19:00) of Cerebrospinal Fluid (CSF) Amyloid Beta During Sleep Induction and Sleep Deprivation Between 01:00 and 11:00 From Baseline | Baseline = 07:00 to 19:00; Intervention period = 01:00 to 11:00 | Overnight (01:00 to 11:00) differences in CSF amyloid beta from baseline (07:00 to 19:00) between 1) sleep-deprived and control participants and 2) sleep-induced and control participants. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sleep Induction 6.5-7.5 grams of sodium oxybate
Sodium Oxybate: Sodium oxybate h.s. | 11 |
| Sleep Deprivation Sleep deprivation for up to 36 hours with no naps or other sleep periods
Sleep deprivation: 36hr sleep deprivation | 12 |
| Control Participant will sleep as normal under the same controlled conditions in a clinical research unit | 12 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Sleep Deprivation | Control | Sleep Induction | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 12 Participants | 11 Participants | 35 Participants |
| Age, Continuous | 42.0 years | 42.7 years | 45.5 years | 43.3 years |
| Region of Enrollment United States | 12 Participants | 12 Participants | 11 Participants | 35 Participants |
| Sex: Female, Male Female | 6 Participants | 8 Participants | 5 Participants | 19 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 6 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 11 / 12 | 9 / 12 | 11 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Percent Increase From Mean Baseline (07:00 to 19:00) of Cerebrospinal Fluid (CSF) Amyloid Beta During Sleep Induction and Sleep Deprivation Between 01:00 and 11:00 From Baseline
Overnight (01:00 to 11:00) differences in CSF amyloid beta from baseline (07:00 to 19:00) between 1) sleep-deprived and control participants and 2) sleep-induced and control participants.
Time frame: Baseline = 07:00 to 19:00; Intervention period = 01:00 to 11:00
Population: Participants in good general health who had CSF collected every 2 hours for 36 hours while undergoing with sleep deprivation, sleep induction with drug, or control conditions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sleep Induction | Percent Increase From Mean Baseline (07:00 to 19:00) of Cerebrospinal Fluid (CSF) Amyloid Beta During Sleep Induction and Sleep Deprivation Between 01:00 and 11:00 From Baseline | 113 percent increase from mean baseline | Standard Error 5.7 |
| Sleep Deprivation | Percent Increase From Mean Baseline (07:00 to 19:00) of Cerebrospinal Fluid (CSF) Amyloid Beta During Sleep Induction and Sleep Deprivation Between 01:00 and 11:00 From Baseline | 123 percent increase from mean baseline | Standard Error 6.6 |
| Control | Percent Increase From Mean Baseline (07:00 to 19:00) of Cerebrospinal Fluid (CSF) Amyloid Beta During Sleep Induction and Sleep Deprivation Between 01:00 and 11:00 From Baseline | 106 percent increase from mean baseline | Standard Error 5.6 |
Comparison: Mixed linear modeling of change in overnight amyloid beta concentrations from waking baseline between 01:00 and 11:00. Data provided for amyloid beta-40.p-value: 0.07Mixed Models Analysis
Comparison: Mixed linear modeling of change in overnight amyloid beta concentrations from waking baseline between 01:00 and 11:00. Data provided for amyloid beta-40.p-value: 1Mixed Models Analysis