Turning Dexmedetomidine Into a Powerful Anesthetic That Can be Rapidly and Completely Reversed

In this study, the investigators will explore Atipamezole & caffeine's ability to facilitate the emergence from anesthesia. Each subject will visit UChicago 4 times. The first time for informed consent. The second time for a complete physical exam to ensure that the subjects are healthy. Then there are 2 sedation sessions. Subjects get an honorarium for each sedation session.

Study Overview

• Status: Withdrawn
• Conditions: Emergence From Anesthesia
• Intervention / Treatment: Drug: Atipamezole & Caffeine; Drug: Dexmedetomidine Hydrochloride & Saline

Detailed Description

Each subject will attend 3 sessions to complete the study. In the first session, an anesthesiologist will take a medical history and perform a physical examination on the subject. A baseline EKG and urine drug screen test will be obtained. If the subject meets the criteria for the study, healthy and drug-free, the risks involved in the study will be covered in detail. If the subject is willing, then that subject will be enrolled in the study and a detailed informed consent form will covered in detail. Prior to signing the consent form the subject will be required to describe the risks involved in the study in their own words, showing that each subject understand. For each session, subjects will be asked not to eat and drink 8 hours prior to the study in order to minimize the potential risk for aspiration during anesthesia

Once the subject is checked in, a peripheral intravenous catheter (IV) will be inserted on one of the arms. A second IV will be inserted to the other arm. After the IV insertion, American Society of Anesthesiologists (ASA) standard monitoring, including EKG, blood pressure (BP), respiratory rate, pulse oximetry and temperature, will be used to assess the subject. An EEG monitor probe will be applied to the forehead skin as well. The subject will then be asked to breathe 100% reof Precedex (2 g/kg), via pump, across 10 minutes. There will be a 5 minute interval to allow the drug to equilibrate. Then p or saline (control). The face mask will stay in place throughout the procedure. For the experiment described, Ati: Dex ratio is 1:1. The investigators will be blind to the injection.

The investigators will measure the time when the drug injections are complete to the awakening of the subject. The investigators will record the time until the subject's eyes open, and the time until the subject can respond to the command to grip the hand of the attending physician. When the subject is awake and alert (oriented to time, place and name), the subject will perform psychomotor tests to measure his cognitive function. The subject will be required to complete a simple set of cognitive tests to determine if they are still impaired by the sedative. Both "control" and test subjects will be required to complete the same tests. Tests include one for hand-eye coordination by tracking a randomly moving circle on a computer screen with a cross controlled by a mouse. Reaction time is measured by asking the subject to press a button when the subject hears a sound. The tests will be repeated every 15 minutes for 90 minutes after waking. This will allow the investigators to get a recovery time course.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Aaron Fox, PHD; Phone Number: (773) 702-0021; Email: aaronfox@uchicago.edu
• Study Contact Backup: Name: Jimmy Xie, MD, PHD; Phone Number: (773) 702-2667; Email: JXie@dacc.uchicago.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
      • Contact: Aaron Fox, PHD; Phone Number: 773-702-0021; Email: aaronfox@uchicago.edu
      • Contact: Zheng (Jimmy) Xie, MD, PHD; Email: JXie@dacc.uchicago.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 39 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age >21 or <40
2. ASA physical status = 1 (normal healthy patient without systematic diseases or conditions)
3. Metabolic Equivalents of Functional Capacity (METs) > 5
4. Low risk for Obstructive Sleep Apnea (OSA) based on the screening test (STOP-bang score established by American Society of Sleep Apnea): Yes to < 3 items- high risk of OSA
5. No history Arrhythmia, such as heart block (Baseline EKG will be obtained during the history and physical session), seizure, liver and kidney diseases
6. BMI <30 kg/m2
7. No history of any mental illness
8. No history of drugs or alcohol abuse (an urine drug screen test required)

Exclusion Criteria:

1. Age <21 or >40
2. ASA physical status > 1 (normal healthy patient with systematic diseases or conditions)
3. Metabolic Equivalents of Functional Capacity (METs)<5
4. High risks for Obstructive Sleep Apnea (OSA) based on the screening test (STOP-bang score established by American Society of Sleep Apnea): Yes to > 3 items- high risk of OSA
5. History Arrhythmia (Baseline EKG will be obtained during the history and physical session), seizure, liver and kidney diseases
6. BMI >30 kg/m2
7. History of any mental illness
8. History of drugs or alcohol abuse (an urine drug screen test required)
9. Female subjects with positive urine pregnancy test, which will be performed before each sedation session

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Phase 1: Atipamezole & caffeine's in a 1:1 ratio; Is this arm, subjects will be randomized to IV administration of Atipamezole & caffeine's in a 1:1 ratio	Drug: Atipamezole & Caffeine; In this arm, subjects will be infused with Atipamezole (2 g/kg) and caffeine (15 mg/kg) across 5 minutes; Other Names: Antisedan
Placebo Comparator: Phase 1: Precedex & Saline in a 1:1 ratio; Is this arm, subjects will be randomized to receive IV administration of Precedex & Saline in a 1:1 ratio	Drug: Dexmedetomidine Hydrochloride & Saline; In this arm, subjects will be infused with Precedex & Saline at 15 mg/kg across 5 minutes; Other Names: Precedex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The time when the drug injections are complete to the awakening of the subject.	We will record the time until the subject's eyes open, and the time until the subject can respond to the command to grip the hand of the attending physician	1 Day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure Cognitive Function	Subjects will be asked to track randomly moving circle on a computer screen with a cross controlled by a mouse	This test will be repeated every 15 Minutes for 90 Minutes after the subject has awakened]
Measure Reaction Time	Subjects will be asked to press a button when he/ she hears a sound	This test will be repeated every 15 Minutes for 90 Minutes after the subject has awakened]

Collaborators and Investigators

• Sponsor: University of Chicago

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2023
• Primary Completion (Anticipated): April 1, 2026
• Study Completion (Anticipated): May 1, 2026

Study Registration Dates

• First Submitted: June 11, 2021
• First Submitted That Met QC Criteria: June 18, 2021
• First Posted (Actual): June 28, 2021

Study Record Updates

• Last Update Posted (Actual): May 17, 2023
• Last Update Submitted That Met QC Criteria: May 15, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Anesthesia; Caffeine; Precedex; Atipamezole; Sedation Recovery
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Purinergic Antagonists; Purinergic Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Adrenergic alpha-Antagonists; Adrenergic alpha-2 Receptor Antagonists; Dexmedetomidine; Caffeine; Atipamezole
• Other Study ID Numbers: IRB21-0922

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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