The Influence of Dexmedetomidine Hypnosis on Cerebrospinal Fluid (CSF) Volume, Brain Diffusion and 'Stiffness' Characteristics.
Primary Purpose
Cerebrospinal Fluid Pressure Increased
Status
Withdrawn
Phase
Early Phase 1
Locations
Study Type
Interventional
Intervention
Dexmedetomidine
Sponsored by
About this trial
This is an interventional diagnostic trial for Cerebrospinal Fluid Pressure Increased focused on measuring dexmedetomidine
Eligibility Criteria
Inclusion Criteria:
- Healthy Males or females between 18 and 40 years of age. Determined to be American Society of Anesthesiologist (ASA) 1 subjects.
- Ability to provide written informed consent.
Exclusion Criteria:
- Subjects with potential difficult airway as determined by the anesthesiologist
- History of or family history of difficulty with anesthesia or sedation procedures
- Known intolerance to dexmedetomidine
- Body mass index >30
- Subjects with any of the following: narcolepsy, obstructive sleep apnea (OSA) and/or abnormal sleeping patterns (including but not limited to those who use a Continuous positive Airway Pressure (C-PAP) machine, sleeping during the day, using medication to fall asleep, subjects reporting snoring as determined by self- report using Snoring, Tiredness, Observed apnea, Blood pressure, Body mass index, Age, Neck circumference and Gender (STOP-BANG) questionnaire (i) for undiagnosed OSA (3 or more 'yes' answers will exclude) and/or medical history;
- Subjects with a history of restless leg syndrome as determined by self-report and/or medical history;
- Use, in the past two weeks, of psychoactive medications (four weeks for fluoxetine) or medications that may affect brain function (including but not limited to opioid analgesics, antidepressants, antipsychotics, benzodiazepines and barbiturates) as determined by self-report and/or medical history;
- Current or past Diagnostic and Statistical Manual of Mental Disorders (DSM-V) diagnosis of a psychiatric disorder if it was severe enough to require the use of medications and or hospitalization to treat the condition.
- Major medical problems that can impact brain function (e.g., problems of the Central Nervous System including seizures and psychosis; cardiovascular disease including hypertension and arrhythmias; metabolic, autoimmune, endocrine disorders) as determined by self-report, medical history and/or clinical exam;
- Hepatic dysfunction or impairment as determined by subjects' self-reported history
- Head trauma with loss of consciousness for more than 60 minutes as determined by self-report and/or medical history;
- Positive urine test for controlled substances (cocaine, methamphetamine, amphetamines, opioids, cannabinoids, benzodiazepines and barbiturates) at the screening visit and at each visit of imaging study and neuropsychological assessment;
- Positive urine pregnancy test;
- Nursing mothers will be excluded
- Presence of ferromagnetic objects in the body that are contraindicated for MRI of the head (including but not limited to pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips, metallic prostheses, permanent eyeliner, large tattoos, implanted delivery pump, or shrapnel fragments) or fear of enclosed spaces as determined by the self-report checklist.
- Fear of enclosed spaces (claustrophobia) as determined by self-report and medical history.
- Cannot lie comfortably flat on the back for up to 3 hours in the MRI scanner as determined by self- report.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dexmedetomidine induced sleep patients
Arm Description
All subjects will be measured for CSF volume, diffusion parameters and mechanical 'stiffness' of the brain during wakefulness and during sleep-induced with dexmedetomidine (DEXM).
Outcomes
Primary Outcome Measures
CSF volume increase by 10%
We hypothesize that CSF volume (as measured by T1 relaxation) will expand by 10% with DEXM- induced sleep compared to wakefulness. The increase in CSF volume during DEXM-induced sleep occurs because DEXM lowers central norepinephrine tone and sleep causes an increase in the interstitial fluid (ISF) volume (cell volume shrinks). MRI will take place 30 minutes after dexmedetomidine infusion.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03757897
Brief Title
The Influence of Dexmedetomidine Hypnosis on Cerebrospinal Fluid (CSF) Volume, Brain Diffusion and 'Stiffness' Characteristics.
Official Title
The Influence of Dexmedetomidine Hypnosis on Cerebrospinal Fluid (CSF) Volume, Brain Diffusion and 'Stiffness' Characteristics
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Withdrawn
Why Stopped
The investigators were unable to implement a MRI compatible EEG for use in human subjects (equipment and technical issues).
Study Start Date
December 2021 (Anticipated)
Primary Completion Date
December 2022 (Anticipated)
Study Completion Date
December 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary goal is to quantify cerebrospinal fluid (CSF) volume, diffusion characteristics and mechanical properties of brain tissue at two states of arousal.
Detailed Description
The primary goal is to quantify cerebrospinal fluid (CSF) volume, diffusion characteristics and mechanical properties of brain tissue at two states of arousal:
Resting, awake state
During sleep with low-dose intravenous infusion of dexmedetomidine (titrated to a Bispectral index (BIS) of 60-70)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cerebrospinal Fluid Pressure Increased
Keywords
dexmedetomidine
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Model Description
This is a preliminary interventional trial in which participants will serve as their own controls.
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dexmedetomidine induced sleep patients
Arm Type
Experimental
Arm Description
All subjects will be measured for CSF volume, diffusion parameters and mechanical 'stiffness' of the brain during wakefulness and during sleep-induced with dexmedetomidine (DEXM).
Intervention Type
Drug
Intervention Name(s)
Dexmedetomidine
Other Intervention Name(s)
DEXM
Intervention Description
The standard dosing of 1mcg/kg will be implemented over 10 minutes followed by a maintenance infusion of 0.2-1.0 titrated to a the target BIS (60-70) during the 20 minutes prior to MRI.
Primary Outcome Measure Information:
Title
CSF volume increase by 10%
Description
We hypothesize that CSF volume (as measured by T1 relaxation) will expand by 10% with DEXM- induced sleep compared to wakefulness. The increase in CSF volume during DEXM-induced sleep occurs because DEXM lowers central norepinephrine tone and sleep causes an increase in the interstitial fluid (ISF) volume (cell volume shrinks). MRI will take place 30 minutes after dexmedetomidine infusion.
Time Frame
2 hours 30 minutes
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy Males or females between 18 and 40 years of age. Determined to be American Society of Anesthesiologist (ASA) 1 subjects.
Ability to provide written informed consent.
Exclusion Criteria:
Subjects with potential difficult airway as determined by the anesthesiologist
History of or family history of difficulty with anesthesia or sedation procedures
Known intolerance to dexmedetomidine
Body mass index >30
Subjects with any of the following: narcolepsy, obstructive sleep apnea (OSA) and/or abnormal sleeping patterns (including but not limited to those who use a Continuous positive Airway Pressure (C-PAP) machine, sleeping during the day, using medication to fall asleep, subjects reporting snoring as determined by self- report using Snoring, Tiredness, Observed apnea, Blood pressure, Body mass index, Age, Neck circumference and Gender (STOP-BANG) questionnaire (i) for undiagnosed OSA (3 or more 'yes' answers will exclude) and/or medical history;
Subjects with a history of restless leg syndrome as determined by self-report and/or medical history;
Use, in the past two weeks, of psychoactive medications (four weeks for fluoxetine) or medications that may affect brain function (including but not limited to opioid analgesics, antidepressants, antipsychotics, benzodiazepines and barbiturates) as determined by self-report and/or medical history;
Current or past Diagnostic and Statistical Manual of Mental Disorders (DSM-V) diagnosis of a psychiatric disorder if it was severe enough to require the use of medications and or hospitalization to treat the condition.
Major medical problems that can impact brain function (e.g., problems of the Central Nervous System including seizures and psychosis; cardiovascular disease including hypertension and arrhythmias; metabolic, autoimmune, endocrine disorders) as determined by self-report, medical history and/or clinical exam;
Hepatic dysfunction or impairment as determined by subjects' self-reported history
Head trauma with loss of consciousness for more than 60 minutes as determined by self-report and/or medical history;
Positive urine test for controlled substances (cocaine, methamphetamine, amphetamines, opioids, cannabinoids, benzodiazepines and barbiturates) at the screening visit and at each visit of imaging study and neuropsychological assessment;
Positive urine pregnancy test;
Nursing mothers will be excluded
Presence of ferromagnetic objects in the body that are contraindicated for MRI of the head (including but not limited to pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips, metallic prostheses, permanent eyeliner, large tattoos, implanted delivery pump, or shrapnel fragments) or fear of enclosed spaces as determined by the self-report checklist.
Fear of enclosed spaces (claustrophobia) as determined by self-report and medical history.
Cannot lie comfortably flat on the back for up to 3 hours in the MRI scanner as determined by self- report.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Helene Benveniste, MD, PhD
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
The Influence of Dexmedetomidine Hypnosis on Cerebrospinal Fluid (CSF) Volume, Brain Diffusion and 'Stiffness' Characteristics.
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