Neurochemical Mechanisms of the Awake vs. Anesthetized Brain

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05435560

Collaborator

Boston University (Other)

Enrollment

Location

Arms

11.6

Anticipated Duration (Months)

2.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators will be studying the sedative drug dexmedetomidine using hybrid PET/fMRI/EEG imaging to better understand the neuropharmacology of anesthesia/artificially induced sleep.

Condition or Disease	Intervention/Treatment	Phase
Anesthesia Healthy	Drug: Dexmedetomidine Drug: Saline	Early Phase 1

Detailed Description

A group of healthy volunteers will undergo simultaneous PET/fMRI/EEG imaging under two different conditions: while being administered a sedative (dexmedetomidine), and while being administered a normal saline infusion, as a control. The order of these two scans will be randomized, and the study design is open label (ie subjects and investigators know which session will be the control scan and which one will be the sedative scan). Investigators hope that by comparing the results of the sedative and control scans, the different neuromodulatory states involved in the transition from wakefulness to medically induced vs naturally occurring sleep can be better understood.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Characterizing the Neuropharmacology of Dexmedetomidine Through Trimodal Imaging

Actual Study Start Date :

Apr 12, 2022

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dexmedetomidine During the imaging scan subjects will receive an initial 1µg/kg bolus of dexmedetomidine up to a maximum dose of 80 µg, infused through IV over 10 minutes. After the bolus has been administered, a constant infusion of up to 0.6 µg/kg/hr (0.01 µg/kg/min) of dexmedetomidine will be maintained for the remainder of the scan (about 60 minutes).	Drug: Dexmedetomidine During the imaging scan subjects will receive an initial bolus of dexmedetomidine over 10 minutes. After the bolus has been administered, a constant infusion of dexmedetomidine will be maintained for the remainder of the scan (about 60 minutes). Other Names: Precedex
Placebo Comparator: Saline A saline infusion will be used as a placebo comparator for the dexmedetomidine infusion. It will be administered in the same manner and dosages as the dexmedetomidine.	Drug: Saline During the imaging scan subjects will receive an initial bolus of saline over 10 minutes. After the bolus has been administered, a constant infusion of saline will be maintained for the remainder of the scan (about 60 minutes).

Arm

Intervention/Treatment

Experimental: Dexmedetomidine

During the imaging scan subjects will receive an initial 1µg/kg bolus of dexmedetomidine up to a maximum dose of 80 µg, infused through IV over 10 minutes. After the bolus has been administered, a constant infusion of up to 0.6 µg/kg/hr (0.01 µg/kg/min) of dexmedetomidine will be maintained for the remainder of the scan (about 60 minutes).

Drug: Dexmedetomidine

During the imaging scan subjects will receive an initial bolus of dexmedetomidine over 10 minutes. After the bolus has been administered, a constant infusion of dexmedetomidine will be maintained for the remainder of the scan (about 60 minutes).

Other Names:

Precedex

Placebo Comparator: Saline

A saline infusion will be used as a placebo comparator for the dexmedetomidine infusion. It will be administered in the same manner and dosages as the dexmedetomidine.

Drug: Saline

During the imaging scan subjects will receive an initial bolus of saline over 10 minutes. After the bolus has been administered, a constant infusion of saline will be maintained for the remainder of the scan (about 60 minutes).

Outcome Measures

Primary Outcome Measures

Brain positron emission tomography (PET) imaging signals. [2 hours]
Changes in dopamine receptor availability will be quantified from brain PET images.
Functional magnetic resonance imaging (fMRI) signals. [2 hours]
fMRI measures of hemodynamic responses.
Differences in electroencephalography (EEG) measures between arousal and anesthesia. [2 hours]
Arousal states will be characterized from changes in the EEG power spectrum.

Secondary Outcome Measures

Heart rate [2 hours]
Heart rate variability.
Pulse oximetry [2 hours]
Amplitude of pulse oximetry signal.
Respiratory physiology [2 hours]
Breathing rate (breaths per minute).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Adults aged 18-45.
No contraindications to MRI or PET scanning.

Exclusion Criteria:

Contraindications to fMRI scanning and PET scanning (including presence of a cardiac pacemaker or pacemaker wires, metallic particles in the body, vascular clips in the head or previous neurosurgery, prosthetic heart valves, claustrophobia);
Pregnancy or breast feeding;
Current or past history of major medical, neurological, or psychiatric condition;
History of major head trauma;
Any cardiovascular disorders, including heart disorders or high blood pressure [>155/95];
Breathing problems such as severe asthma;
Bleeding disorder, or use of anticoagulants;
Bladder obstruction, urinary problems, or history of impaired elimination;
Known kidney or liver problems;
Intestinal blockage;
Raynaud syndrome
Peripheral nerve injury;
Diabetes;
Glaucoma;
Sleep disorder, such as sleep apnea, insomnia, or narcolepsy
Current use of any drugs that affect sleep
Current or recent use of medications (neurological or psychiatric) affecting brain function
Current or past history of chronic pain (assessed at discretion of PI);
History of allergic reactions
History of chronic obstructive pulmonary diseases
Ulcerative skin conditions or other dermatologic conditions which could interfere with blood pressure cuff placement
Body mass index above 30
Current smoker
Lack of current health insurance coverage
Employed under the direct supervision of the investigators conducting the research
Hair in dreadlocks, twists, or braids that cannot be removed
Eczema on the scalp or face