A Study to Determine if Caffeine Accelerates Emergence From Propofol Anesthesia

• Sponsor: University of Chicago (Other)
• Overall Status: Completed
• CT.gov ID: NCT03360903
• Collaborator: National Institutes of Health (NIH) (NIH), National Institute of General Medical Sciences (NIGMS) (NIH)
• Enrollment: 8
• Location: 1
• Arms: 2
• Actual Duration (Months): 16.9
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

At present clinicians have no way to reverse anesthesia. Patients wake when their bodies clear the anesthetic. Most people wake quickly, but some do not. All patients have memory and other cognitive problems after waking from anesthesia. In studies on animals, the investigators observed that caffeine caused rats to wake much more rapidly from propofol anesthesia. This was true for all the animals tested. The investigators would like to see if this holds true in humans. Will caffeine accelerate waking from anesthesia? Will it reverse the cognitive deficits associated with anesthesia, after waking?

The propose investigators carrying out a modest trial with 8 test subjects. Each volunteer will be anesthetized twice. Each volunteer will be anesthetized one time and receive an infusion of saline (placebo control), without the aid of any other drugs and the other time the volunteer will receive an infusion of a relatively low dose of caffeine. The order of saline versus caffeine will be randomized and the study will be done in a double blind manner. We will determine whether emergence from propofol anesthesia will be significantly accelerated by the caffeine infusion. And whether any adverse events are observed.

Condition or Disease	Intervention/Treatment	Phase
Anesthesia	Drug: Placebo; Drug: Caffeine	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Randomized, Double-Blinded, Placebo-Controlled Study to Determine if Caffeine Citrate Accelerates Emergence From Anesthesia
• Actual Study Start Date: Jan 2, 2018
• Actual Primary Completion Date: Dec 31, 2018
• Actual Study Completion Date: Jun 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Placebo then Caffeine Anesthetized volunteers will be allowed to wake after injection of saline (placebo control) followed by a washout period and then anesthetized again and allowed to wake after injection of caffeine (15 mg/ kg).	Drug: Placebo; Anesthetized volunteers will be allowed to wake after injection of saline (placebo control). Other Names: Saline; Drug: Caffeine; Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg). Other Names: Caffeine citrate
Experimental: Caffeine then Placebo Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg) followed by a washout period and then anesthetized again and allowed to wake after injection of saline (placebo control).	Drug: Placebo; Anesthetized volunteers will be allowed to wake after injection of saline (placebo control). Other Names: Saline; Drug: Caffeine; Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg). Other Names: Caffeine citrate

Outcome Measures

Primary Outcome Measures

1. Waking Time - Time Between Terminating Anesthesia and Subject Opening Eyes. [15 minutes]

   The goal of the study is to determine whether caffeine speeds emergence from anesthesia. The time between terminating delivery of anesthetic and the subject opening their eyes will be measured. The time to "emerge" from anesthesia will be defined as the time between terminating the anesthesia and the test subject opening their eyes.

Secondary Outcome Measures

1. Cognitive Test1 - Visual Analog Scale [Up to 120 minutes after terminating anesthesia.]

   Normally patients receiving anesthesia exhibit significant cognitive problems for hours after anesthesia is terminated. The goal is to determine whether caffeine helps ameliorate the cognitive issues. Fifteen minutes after terminating anesthesia each subject will be asked to complete a series of psychomotor tests, if they are able. Otherwise the testing started at 30 minutes. The tests will be repeated every 15 minutes. The first test, a visual analog scale (VAS) test consisted of two 100-mm lines, each labelled with of "feel good" or "feel bad" displayed on a computer screen. Test subjects will be asked to rate how they currently felt by placing a cursor on each of the line (0=not at all, 100=extremely). The test will be repeated every 15 minutes.

2. Cognitive Test2 - Sternberg Test of Memory [Up to 120 minutes after terminating anesthesia.]

   Normally patients receiving anesthesia exhibit significant cognitive problems for hours after anesthesia is terminated. The goal is to determine whether caffeine helps ameliorate the cognitive issues. The test will be applied at 15 minutes following anesthesia, if the subject is awake and then repeated every 15 minutes. In the Sternberg Test of Memory (STM) participants are asked to memorize a string of numbers. Afterwards, a computer will flash a series of random numbers on the screen and the participant is asked whether the number on the computer screen are part of the earlier string or not. In three rounds, participants are given a string of 2, then 4, then 6 numbers. The latency until the subject answers the question is also monitored.

3. Cognitive Test3 - Divided Attention Task [Up to 120 minutes after terminating anesthesia.]

   Normally patients receiving anesthesia exhibit significant cognitive problems for hours after anesthesia is terminated. The goal is to determine whether caffeine helps ameliorate the cognitive issues. The test is first applied at 15 minutes following anesthesia, if the subject is awake and then repeated every 15 minutes. In the Divided Attention Task (DAT), participants are asked to fly an airplane over the center of a winding road with a joystick and simultaneously press a button whenever targets randomly flash on the screen. The computer program tracks the root mean squared (RMS) deviation of the plane from the center of the road and the latency for pressing the trigger when the target appears.

4. Bispectral Index [Up to 120 minutes after terminating anesthesia.]

   A bispectral index (BIS) measurement system is employed to measure depth of anesthesia. In particular, we wish to determine whether BIS exhibits more rapid recovery after caffeine compared to control.

5. Mean Arterial Blood Pressure [Up to 120 minutes after terminating anesthesia.]

   This measurement is made in order to determine whether caffeine alters blood pressure in a deleterious manner.

6. Heart Rate [Up to 120 minutes after terminating anesthesia.]

   This measurement is made in order to determine whether caffeine alters heart rate in a deleterious manner.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 25 Years to 40 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Age 25-40.

2. Male.

3. Normal healthy subject without systematic diseases or conditions.

4. Metabolic Equivalents of Functional Capacity >= 5.

5. 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

6. No History of Arrhythmia (Baseline EKG will be obtained during the history and physical session), seizure, liver and kidney diseases.

7. BMI < 30 kg/m2.

8. No history of prior difficulty with anesthesia.

9. No personal or family history of malignant hyperthermia.

10. No history of any mental illness.

11. No history of drugs or alcohol abuse (urine drug screens required).

12. Subjects capable of giving consent.

13. Living less than 30 miles away from University of Chicago.

14. No history of seizure disorders.

15. No history of head trauma.

Exclusion Criteria:

1. Age <25 or >40.

2. Female.

3. ASA physical status > 1 (normal healthy subject without systematic diseases or conditions)

4. Metabolic Equivalents of Functional Capacity (METs) < 5.

5. 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

6. History Arrhythmia (Baseline EKG will be obtained during the history and physical session), seizure, liver and kidney diseases

7. BMI>30 kg/m2.

8. Prior difficulty with anesthesia.

9. Personal or family history of malignant hyperthermia.

10. History of any mental illness.

11. History of drugs or alcohol abuse (urine drug screens required)

12. Subjects not capable of giving consent

13. Living more than 30 miles away from University of Chicago.

14. History of seizure disorders.

15. History of head trauma.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Chicago	Chicago	Illinois	United States	60637

Sponsors and Collaborators

• University of Chicago
• National Institutes of Health (NIH)
• National Institute of General Medical Sciences (NIGMS)

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 24, 2019

More Information

Publications

None provided.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT03360903
• Other Study ID Numbers: IRB17-1174; 1R01GM116119
• First Posted: Dec 4, 2017
• Last Update Posted: Nov 18, 2019
• Last Verified: Oct 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Caffeine

Study Results

Participant Flow

Arm/Group Title	Placebo Then Caffeine	Caffeine Then Placebo
Arm/Group Description	Anesthetized volunteers will be allowed to wake after injection of saline (placebo control) followed by a washout period and then anesthetized again and allowed to wake after injection of caffeine (15 mg/ kg). Placebo: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control). Other Names: Saline Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg). Other Names: Caffeine citrate	Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg) followed by a washout period and then anesthetized again and allowed to wake after injection of saline (placebo control). Placebo: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control). Other Names: Saline Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg). Other Names: Caffeine citrate
Period Title: First Intervention
STARTED	4	4
COMPLETED	4	4
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	4	4
COMPLETED	4	4
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	4	4
COMPLETED	4	4
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo Then Caffeine	Caffeine Then Placebo	Total
Arm/Group Description	Anesthetized volunteers will be allowed to wake after injection of saline (placebo control) followed by a washout period and then anesthetized again and allowed to wake after injection of caffeine (15 mg/ kg). Placebo: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control). Other Names: Saline Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg). Other Names: Caffeine citrate	Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg) followed by a washout period and then anesthetized again and allowed to wake after injection of saline (placebo control). Placebo: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control). Other Names: Saline Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg). Other Names: Caffeine citrate	Total of all reporting groups
Overall Participants	4	4	8
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.8 (2.4)	27.3 (3.2)	27.0 (2.6)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	4 100%	4 100%	8 100%
Race/Ethnicity, Customized (Count of Participants)
African American	0 0%	1 25%	1 12.5%
Asian	1 25%	0 0%	1 12.5%
Hispanic	1 25%	1 25%	2 25%
Caucasian	1 25%	1 25%	2 25%
Mixed Race	1 25%	1 25%	2 25%
Region of Enrollment (participants) [Number]
United States	4 100%	4 100%	8 100%

Outcome Measures

1. Primary Outcome

Title	Waking Time - Time Between Terminating Anesthesia and Subject Opening Eyes.
Description	The goal of the study is to determine whether caffeine speeds emergence from anesthesia. The time between terminating delivery of anesthetic and the subject opening their eyes will be measured. The time to "emerge" from anesthesia will be defined as the time between terminating the anesthesia and the test subject opening their eyes.
Time Frame	15 minutes

Outcome Measure Data

Analysis Population Description

Due to technical problems during the study, data was not collected and analyzed.

Arm/Group Title	Placebo	Caffeine
Arm/Group Description	Participants received a saline infusion	Participants received a caffiene infusion
Measure Participants	0	0

2. Secondary Outcome

Title	Cognitive Test1 - Visual Analog Scale
Description	Normally patients receiving anesthesia exhibit significant cognitive problems for hours after anesthesia is terminated. The goal is to determine whether caffeine helps ameliorate the cognitive issues. Fifteen minutes after terminating anesthesia each subject will be asked to complete a series of psychomotor tests, if they are able. Otherwise the testing started at 30 minutes. The tests will be repeated every 15 minutes. The first test, a visual analog scale (VAS) test consisted of two 100-mm lines, each labelled with of "feel good" or "feel bad" displayed on a computer screen. Test subjects will be asked to rate how they currently felt by placing a cursor on each of the line (0=not at all, 100=extremely). The test will be repeated every 15 minutes.
Time Frame	Up to 120 minutes after terminating anesthesia.

Outcome Measure Data

Analysis Population Description

Due to technical problems during the study, data was not collected and analyzed.

Arm/Group Title	Placebo	Caffeine
Arm/Group Description	Participants received a saline infusion	Participants received a caffiene infusion
Measure Participants	0	0

3. Secondary Outcome

Title	Cognitive Test2 - Sternberg Test of Memory
Description	Normally patients receiving anesthesia exhibit significant cognitive problems for hours after anesthesia is terminated. The goal is to determine whether caffeine helps ameliorate the cognitive issues. The test will be applied at 15 minutes following anesthesia, if the subject is awake and then repeated every 15 minutes. In the Sternberg Test of Memory (STM) participants are asked to memorize a string of numbers. Afterwards, a computer will flash a series of random numbers on the screen and the participant is asked whether the number on the computer screen are part of the earlier string or not. In three rounds, participants are given a string of 2, then 4, then 6 numbers. The latency until the subject answers the question is also monitored.
Time Frame	Up to 120 minutes after terminating anesthesia.

Outcome Measure Data

Analysis Population Description

Due to technical problems during the study, data was not collected and analyzed.

Arm/Group Title	Placebo	Caffeine
Arm/Group Description	Participants received a saline infusion	Participants received a caffiene infusion
Measure Participants	0	0

4. Secondary Outcome

Title	Cognitive Test3 - Divided Attention Task
Description	Normally patients receiving anesthesia exhibit significant cognitive problems for hours after anesthesia is terminated. The goal is to determine whether caffeine helps ameliorate the cognitive issues. The test is first applied at 15 minutes following anesthesia, if the subject is awake and then repeated every 15 minutes. In the Divided Attention Task (DAT), participants are asked to fly an airplane over the center of a winding road with a joystick and simultaneously press a button whenever targets randomly flash on the screen. The computer program tracks the root mean squared (RMS) deviation of the plane from the center of the road and the latency for pressing the trigger when the target appears.
Time Frame	Up to 120 minutes after terminating anesthesia.

Outcome Measure Data

Analysis Population Description

Due to technical problems during the study, data was not collected and analyzed.

Arm/Group Title	Placebo	Caffeine
Arm/Group Description	Participants received a saline infusion	Participants received a caffiene infusion
Measure Participants	0	0

5. Secondary Outcome

Title	Bispectral Index
Description	A bispectral index (BIS) measurement system is employed to measure depth of anesthesia. In particular, we wish to determine whether BIS exhibits more rapid recovery after caffeine compared to control.
Time Frame	Up to 120 minutes after terminating anesthesia.

Outcome Measure Data

Analysis Population Description

Due to technical problems during the study, data was not collected and analyzed.

Arm/Group Title	Placebo	Caffeine
Arm/Group Description	Participants received a saline infusion	Participants received a caffiene infusion
Measure Participants	0	0

6. Secondary Outcome

Title	Mean Arterial Blood Pressure
Description	This measurement is made in order to determine whether caffeine alters blood pressure in a deleterious manner.
Time Frame	Up to 120 minutes after terminating anesthesia.

Outcome Measure Data

Analysis Population Description

Due to technical problems during the study, data was not collected and analyzed.

Arm/Group Title	Placebo	Caffeine
Arm/Group Description	Participants received a saline infusion	Participants received a caffiene infusion
Measure Participants	0	0

7. Secondary Outcome

Title	Heart Rate
Description	This measurement is made in order to determine whether caffeine alters heart rate in a deleterious manner.
Time Frame	Up to 120 minutes after terminating anesthesia.

Outcome Measure Data

Analysis Population Description

Due to technical problems during the study, data was not collected and analyzed.

Arm/Group Title	Placebo	Caffeine
Arm/Group Description	Participants received a saline infusion	Participants received a caffiene infusion
Measure Participants	0	0

Adverse Events

Time Frame	4 weeks
Arm/Group Title	Placebo		Caffeine
Arm/Group Description	Participants received a saline infusion		Participants received a caffiene infusion
All Cause Mortality
	Placebo		Caffeine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)
Serious Adverse Events
	Placebo		Caffeine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Caffeine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.