Neurochemical Mechanisms of the Awake vs. Anesthetized Brain

Characterizing the Neuropharmacology of Dexmedetomidine Through Trimodal Imaging

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.

Study Overview

• Status: Recruiting
• Conditions: Healthy; Anesthesia
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Saline

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Irena Bass, BA; Phone Number: 617-726-9034; Email: ibass@mgh.harvard.edu
• Study Contact Backup: Name: Christin Y Sander, PhD; Phone Number: 617-726-9034; Email: csander@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Charlestown, Massachusetts, United States, 02129
      • Recruiting
      • Athinoula A. Martinos Center for Biomedical Imaging
      • Contact: Irena Bass; Phone Number: 617-726-9034; Email: ibass@mgh.harvard.edu
      • Principal Investigator: Christin Sander, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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).

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate	Heart rate variability.	2 hours
Pulse oximetry	Amplitude of pulse oximetry signal.	2 hours
Respiratory physiology	Breathing rate (breaths per minute).	2 hours

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Boston University
• Investigators: Principal Investigator: Christin Y Sander, PhD, Athinoula A. Martinos Center for Biomedical Imaging

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2022
• Primary Completion (Anticipated): April 1, 2023
• Study Completion (Anticipated): April 1, 2023

Study Registration Dates

• First Submitted: April 22, 2022
• First Submitted That Met QC Criteria: June 23, 2022
• First Posted (Actual): June 28, 2022

Study Record Updates

• Last Update Posted (Actual): June 28, 2022
• Last Update Submitted That Met QC Criteria: June 23, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Positron Emission Tomography; Sleep; Magnetic Resonance Imaging; Anesthesia; Dopamine; Electroencephalograpy
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: 2021P003426

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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.: No