- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01094574
Evaluation of Propranolol's Effect on Pain and Inflammation.
Investigation of Analgesic and Anti-inflammatory Effects of Beta-adrenergic Antagonist Propranolol
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This study is a double blind-placebo controlled study in which subjects will be exposed to propranolol infusion during one study day, the opioid alfentanil on another day, and placebo infusion during a third study day. The infusion order will be randomized, and the participant and individual conducting the pain testing will both be blinded to the treatment.
Propranolol, alfentanil, and placebo infusions will be administered intravenously using a computer-controlled infusion pump that can be set to accurately administer a target plasma concentration of drug.
On one study day subjects will receive propranolol at a target concentration of 30ng/ml over 3 hours time. On another study day subjects will receive 100ng/ml alfentanil over 3 hours, and on a third study day subjects will receive placebo (normal saline) using a computer-controlled infusion paradigm.
Sites to be evaluated for response to propranolol and placebo will be established in 2 ways. One will use ultraviolet B (UVB) exposure to create a "sunburn" causing inflammation and pain. The other will be a model of acute injury using an array of micro-needles.
Means of evaluation of injured, and non-injured sites will be pain testing (heat and mechanical pain thresholds will be established), interstitial fluid sampling for detection of pro-inflammatory, and pro-nociceptive cytokines, and laser doppler evaluation of tissue perfusion.
Subjects will be recruited using flyers. Interested participants will contact the study team, their questions will be answered, and an appointment for screening will be made.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
California
-
Stanford, California, United States, 94305
- Stanford University School of Medicine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- ADULT
- OLDER_ADULT
- CHILD
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:1) Age 18-65 2) Skin type II-IV according to classification of Fitzpatrick 3) Willing and able to sign an informed consent form and Health Insurance Portability and Accountability Act (HIPAA) authorization and to comply with study procedures
Exclusion Criteria:1) History of acute or chronic illness that contraindicate the use of propranolol, may hinder study procedures, or confuse interpretation of the data (e.g. cardiac, dermatological, neurological, psychiatric or addictive diseases) 2) Clinically significant cardiovascular, pulmonary, hepatic or renal diseases 3) Pregnant or breast-feeding 4) Intake of prescription drugs with anti/pro-inflammatory action 5) Intake of prescription drugs with anti/pro-analgesic action 6) Inability to abstain from any anti/pro-inflammatory, or analgesic drugs 48 hours before, or during the study session 7) Inability to obtain at least 6 hours of sleep during the night preceding the study session 8) Known sensitivity or allergy to propranolol or alfentanil 9) Any history of drug or alcohol abuse
Study Plan
How is the study designed?
Design Details
- Primary Purpose: BASIC_SCIENCE
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Alfentanil
Experimental inflammation, and tissue injury sites were created, an infusion of alfentanil 100ng/ml was administered over 3 hours using a programmable infusion pump, and data were collected to measure inflammation, pain response, and cytokine levels locally.
|
An infusion of alfentanil 100ng/ml was administered over 3 hours using a programmable infusion pump.
Other Names:
|
ACTIVE_COMPARATOR: Propranolol
Experimental inflammation and tissue injury sites were created, an infusion of propranolol 30ng/ml was administered over 3 hours using a programmable infusion pump, and data were collected to measure inflammation, pain response, and cytokine levels locally.
|
An infusion of propranolol 30ng/ml was administered over 3 hours using a programmable infusion pump.
Other Names:
|
PLACEBO_COMPARATOR: Placebo
Experimental inflammation and tissue injury sites were created, an infusion of normal saline was administered over 3 hours using a programmable infusion pump, and data were collected to measure inflammation, pain response, and cytokine levels locally.
|
An infusion of normal saline was administered over 3 hours using a programmable infusion pump to mimic the 2 drug arms,
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Heat Pain Threshold During Infusion in Non-Inflamed Skin
Time Frame: Participants underwent the pain testing measures at baseline and at 1 and 2 hours after startingthe drug infusion.
|
Degrees Centigrade Heat pain was induced with a thermal sensory analyzer (TSA-II, Medoc Advanced Medical Systems, Durham, North Carolina).
A thermode was placed in contact with skin on the upper thigh.
Starting at a comfortable temperature, the thermode temperature was increased at a measured rate.
Study participants pushed a button of a hand-held device at the onset of pain at which point the thermode immediately reduced the temperature.
Measurements for analgesia were taken at the sites of non-injured skin.
Change form baseline was calculated by subtracting baseline values from the average values obtained 1 and 2 hours after starting the drug infusion.
|
Participants underwent the pain testing measures at baseline and at 1 and 2 hours after startingthe drug infusion.
|
Change From Baseline in Heat Pain Threshold During Infusion in Inflamed Skin
Time Frame: Participants underwent the pain testing measures at baseline and at 1 and 2 hours after startingthe drug infusion.
|
Degrees Centigrade Heat pain was induced with a thermal sensory analyzer (TSA-II, Medoc Advanced Medical Systems, Durham, North Carolina).
A thermode was placed in contact with skin on the upper thigh.
Starting at a comfortable temperature, the thermode temperature was increased at a measured rate.
Study participants pushed a button of a hand-held device at the onset of pain at which point the thermode immediately reduced the temperature.
Measurements for anti-hyperalgesia were taken at the sites of tissue injury.
Change form baseline was calculated by subtracting baseline values from the average values obtained 1 and 2 hours after starting the drug infusion.
|
Participants underwent the pain testing measures at baseline and at 1 and 2 hours after startingthe drug infusion.
|
Change From Baseline in Mechanical Pain Threshold During Infusion in Non-Inflamed Skin
Time Frame: Participants underwent the pain testing measures at baseline and at 1 and 2 hours after startingthe drug infusion.
|
A metal rod of 0.24 mm diameter mounted onto 10 different weights (1.0, 2.0, 4.1, 8.2,16.3,
20, 32.7,49.0,
65.3, and 81.3g) will be placed perpendicularly onto the skin.
Starting with the lightest probe, consecutively heavier probes will be used until a subject reports pain.
Subsequently, the same or the next lighter probe will be used if pain is reported for the preceding stimulus, or the same or the next heavier probe will be used if no pain is reported for the preceding stimulus.The procedure will be repeated until seven perceptional changes (painful/non-painful) are registered.
Measurements for analgesia were taken at the sites of non-injured skin.
Change form baseline was calculated by subtracting baseline values from the average values obtained 1 and 2 hours after starting the drug infusion.
|
Participants underwent the pain testing measures at baseline and at 1 and 2 hours after startingthe drug infusion.
|
Change From Baseline in Mechanical Pain Threshold During Infusion in Inflamed Skin
Time Frame: Participants underwent the pain testing measures at baseline and at 1 and 2 hours after startingthe drug infusion.
|
A metal rod of 0.24 mm diameter mounted onto 10 different weights (1.0, 2.0, 4.1, 8.2,16.3,
20, 32.7,49.0,
65.3, and 81.3g) will be placed perpendicularly onto the skin.
Starting with the lightest probe, consecutively heavier probes will be used until a subject reports pain.
Subsequently, the same or the next lighter probe will be used if pain is reported for the preceding stimulus, or the same or the next heavier probe will be used if no pain is reported for the preceding stimulus.The procedure will be repeated until seven perceptional changes (painful/non-painful) are registered.
Measurements for anti-hyperalgesia were taken at the sites of tissue injury.
Change form baseline was calculated by subtracting baseline values from the average values obtained 1 and 2 hours after starting the drug infusion.
|
Participants underwent the pain testing measures at baseline and at 1 and 2 hours after startingthe drug infusion.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
TNFα (ng/mL) Change From Baseline During Infusion
Time Frame: Tissue samples were collected at baseline, and 2 and 3 hours after starting the drug infusion.
|
TNFα (ng/mL) was measured in interstitial fluid after collecting samples as follows: Microdialysis catheters (very small, custom-made, sterile, semi-permeable, micro-dialysis catheters) were placed after the 1st laser Doppler measurement.
Two catheters were placed at an experimentally inflamed skin site on the left leg.
A continuous infusion of sterile 1% albumin solution was started using a programmable pump set at a rate of 2.5µl/min.
Samples were collected hourly throughout the remainder of the study day.
Samples for analysis were collected before, and 2 and 3 hours after starting the drug infusion.
Difference form baseline was calculated by subtracting the baseline concentration form the average concentration determined in samples collected during drug infusion.
|
Tissue samples were collected at baseline, and 2 and 3 hours after starting the drug infusion.
|
IL-1β (ng/mL) Change From Baseline During Infusion
Time Frame: Tissue samples were collected at baseline, and 2 and 3 hours after starting the drug infusion.
|
IL-1β (ng/mL) was measured in interstitial fluid after collecting samples as follows: Microdialysis catheters (very small, custom-made, sterile, semi-permeable, micro-dialysis catheters) were placed after the 1st laser Doppler measurement.
Two catheters were placed at an experimentally inflamed skin site on the left leg.
A continuous infusion of sterile 1% albumin solution was started using a programmable pump set at a rate of 2.5µl/min.
Samples were collected hourly throughout the remainder of the study day.
Samples for analysis were collected before, and 2 and 3 hours after starting the drug infusion.
Difference form baseline was calculated by subtracting the baseline concentration form the average concentration determined in samples collected during drug infusion.
|
Tissue samples were collected at baseline, and 2 and 3 hours after starting the drug infusion.
|
IL-2 (ng/mL) Change From Baseline During Infusion
Time Frame: Tissue samples were collected at baseline, and 2 and 3 hours after starting the drug infusion.
|
IL-2 (ng/mL) was measured in interstitial fluid after collecting samples as follows: Microdialysis catheters (very small, custom-made, sterile, semi-permeable, micro-dialysis catheters) were placed after the 1st laser Doppler measurement.
Two catheters were placed at an experimentally inflamed skin site on the left leg.
A continuous infusion of sterile 1% albumin solution was started using a programmable pump set at a rate of 2.5µl/min.
Samples were collected hourly throughout the remainder of the study day.
Samples for analysis were collected before, and 2 and 3 hours after starting the drug infusion.
Difference form baseline was calculated by subtracting the baseline concentration form the average concentration determined in samples collected during drug infusion.
|
Tissue samples were collected at baseline, and 2 and 3 hours after starting the drug infusion.
|
IL-6 (ng/mL) Change From Baseline During Infusion
Time Frame: Tissue samples were collected at baseline, and 2 and 3 hours after starting the drug infusion.
|
IL-6 (ng/mL) was measured in interstitial fluid after collecting samples as follows: Microdialysis catheters (very small, custom-made, sterile, semi-permeable, micro-dialysis catheters) were placed after the 1st laser Doppler measurement.
Two catheters were placed at an experimentally inflamed skin site on the left leg.
A continuous infusion of sterile 1% albumin solution was started using a programmable pump set at a rate of 2.5µl/min.
Samples were collected hourly throughout the remainder of the study day.
Samples for analysis were collected before, and 2 and 3 hours after starting the drug infusion.
Difference form baseline was calculated by subtracting the baseline concentration form the average concentration determined in samples collected during drug infusion.
|
Tissue samples were collected at baseline, and 2 and 3 hours after starting the drug infusion.
|
GMCSF (ng/mL) Change From Baseline During Infusion
Time Frame: Tissue samples were collected at baseline, and 2 and 3 hours after starting the drug infusion.
|
GMCSF (ng/mL) was measured in interstitial fluid after collecting samples as follows: Microdialysis catheters (very small, custom-made, sterile, semi-permeable, micro-dialysis catheters) were placed after the 1st laser Doppler measurement.
Two catheters were placed at an experimentally inflamed skin site on the left leg.
A continuous infusion of sterile 1% albumin solution was started using a programmable pump set at a rate of 2.5µl/min.
Samples were collected hourly throughout the remainder of the study day.
Samples for analysis were collected before, and 2 and 3 hours after starting the drug infusion.
Difference form baseline was calculated by subtracting the baseline concentration form the average concentration determined in samples collected during drug infusion.
|
Tissue samples were collected at baseline, and 2 and 3 hours after starting the drug infusion.
|
IL-8 (ng/mL) Change From Baseline During Infusion
Time Frame: Tissue samples were collected at baseline, and 2 and 3 hours after starting the drug infusion.
|
IL-8 (ng/mL) was measured in interstitial fluid after collecting samples as follows: Microdialysis catheters (very small, custom-made, sterile, semi-permeable, micro-dialysis catheters) were placed after the 1st laser Doppler measurement.
Two catheters were placed at an experimentally inflamed skin site on the left leg.
A continuous infusion of sterile 1% albumin solution was started using a programmable pump set at a rate of 2.5µl/min.
Samples were collected hourly throughout the remainder of the study day.
Samples for analysis were collected before, and 2 and 3 hours after starting the drug infusion.
Difference form baseline was calculated by subtracting the baseline concentration form the average concentration determined in samples collected during drug infusion.
|
Tissue samples were collected at baseline, and 2 and 3 hours after starting the drug infusion.
|
IL-10 (ng/mL) Change From Baseline During Infusion
Time Frame: Tissue samples were collected at baseline, and 2 and 3 hours after starting the drug infusion.
|
IL-10 (ng/mL) was measured in interstitial fluid after collecting samples as follows: Microdialysis catheters (very small, custom-made, sterile, semi-permeable, micro-dialysis catheters) were placed after the 1st laser Doppler measurement.
Two catheters were placed at an experimentally inflamed skin site on the left leg.
A continuous infusion of sterile 1% albumin solution was started using a programmable pump set at a rate of 2.5µl/min.
Samples were collected hourly throughout the remainder of the study day.
Samples for analysis were collected before, and 2 and 3 hours after starting the drug infusion.
Difference form baseline was calculated by subtracting the baseline concentration form the average concentration determined in samples collected during drug infusion.
|
Tissue samples were collected at baseline, and 2 and 3 hours after starting the drug infusion.
|
IL-12 (ng/mL) Change From Baseline During Infusion
Time Frame: Tissue samples were collected at baseline, and 2 and 3 hours after starting the drug infusion.
|
IL-12 (ng/mL) was measured in interstitial fluid after collecting samples as follows: Microdialysis catheters (very small, custom-made, sterile, semi-permeable, micro-dialysis catheters) were placed after the 1st laser Doppler measurement.
Two catheters were placed at an experimentally inflamed skin site on the left leg.
A continuous infusion of sterile 1% albumin solution was started using a programmable pump set at a rate of 2.5µl/min.
Samples were collected hourly throughout the remainder of the study day.
Samples for analysis were collected before, and 2 and 3 hours after starting the drug infusion.
Difference form baseline was calculated by subtracting the baseline concentration form the average concentration determined in samples collected during drug infusion.
|
Tissue samples were collected at baseline, and 2 and 3 hours after starting the drug infusion.
|
Change in Arbitrary Perfusion Units From Baseline During Drug Infusion
Time Frame: Laser doppler images were recorded at baseline and at 2 and 3 hours after starting the drug infusion
|
Laser Doppler images were recorded at baseline and at 2 and 3 hours after starting the drug infusion to provide measurements of peripheral blood flow as an objective measure of inflammation.
Blood flow was quantified by arbitrary perfusion units.
Baseline measurements were subtracted from the average measurements obtained 2 and 3 hours after starting the drug infusion.
|
Laser doppler images were recorded at baseline and at 2 and 3 hours after starting the drug infusion
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Adrenergic beta-Antagonists
- Adrenergic Antagonists
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Antihypertensive Agents
- Vasodilator Agents
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Analgesics, Opioid
- Narcotics
- Propranolol
- Alfentanil
Other Study ID Numbers
- SU-10012009-4121
- 17743
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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