Modulation of CSF Amyloid-beta Concentrations Via Behavioral Sleep Deprivation and Pharmacological Sleep Induction

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.

Study Overview

• Status: Completed
• Conditions: Amyloid-beta
• Intervention / Treatment: Drug: Sodium Oxybate; Behavioral: Sleep deprivation

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).

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63108
      • Washington University Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sleep Induction; 7.5 grams of sodium oxybate	Drug: Sodium Oxybate; Sodium oxybate h.s.; Other Names: Xyrem
Experimental: Sleep Deprivation; Sleep deprivation for up to 36 hours with no naps or other sleep periods	Behavioral: Sleep deprivation; 36hr sleep deprivation
No Intervention: Control; Participant will sleep as normal under the same controlled conditions in a clinical research unit

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline = 07:00 to 19:00; Intervention period = 01:00 to 11:00

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: National Institutes of Health (NIH); National Institute on Aging (NIA)
• Investigators: Principal Investigator: Brendan Lucey, MD, Washington University Medical School

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: January 29, 2014
• First Submitted That Met QC Criteria: February 12, 2014
• First Posted (Estimate): February 14, 2014

Study Record Updates

• Last Update Posted (Actual): April 26, 2018
• Last Update Submitted That Met QC Criteria: March 26, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Nervous System Diseases; Dyssomnias; Sleep Wake Disorders; Neurologic Manifestations; Proteostasis Deficiencies; Amyloidosis; Sleep Deprivation; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Adjuvants, Anesthesia; Sodium Oxybate
• Other Study ID Numbers: 201304030; P50AG005681-30 (U.S. NIH Grant/Contract)