Evaluation of Propranolol's Effect on Pain and Inflammation.

NCT01094574 | Completed Results

• 2 other identifiers: SU-10012009-412117743
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Previous studies have shown that the beta-adrenergic system plays a role in processing pain and the expression of hyperalgesia. Recent studies have investigated the analgesic effects, and potential anti-hyperalgesic effects (using a model of opioid induced (OIH) hyperalgesia) of propranolol, a beta adrenergic antagonist. We plan to further investigate the analgesic effects, and the potential anti inflammatory effects, of propranolol and compare those effects to alfentanil, an opioid of known effect, and placebo

Conditions

Pain Measurement

Outcome Measures

Primary Outcomes (4)

• Change From Baseline in Heat Pain Threshold During Infusion in Non-Inflamed Skin

  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

  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

  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

  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 Outcomes (9)

• TNFα (ng/mL) Change From Baseline During 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

  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

  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

  Tissue samples were collected at baseline, and 2 and 3 hours after starting the drug infusion.

• GMCSF (ng/mL) Change From Baseline During Infusion

  Tissue samples were collected at baseline, and 2 and 3 hours after starting the drug infusion.

Study Arms (3)

Alfentanil

ACTIVE COMPARATOR

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.

Drug: Alfentanil

Propranolol

ACTIVE COMPARATOR

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.

Drug: Propranolol

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Alfentanil DRUG

An infusion of alfentanil 100ng/ml was administered over 3 hours using a programmable infusion pump.

Also known as: No other name

Alfentanil

Propranolol DRUG

An infusion of propranolol 30ng/ml was administered over 3 hours using a programmable infusion pump.

Also known as: No other name

Propranolol

Placebo DRUG

An infusion of normal saline was administered over 3 hours using a programmable infusion pump to mimic the 2 drug arms,

Also known as: Normal Saline

Placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

Sponsors & Collaborators

• Martin Angst: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Interventions

Alfentanil; Propranolol; Saline Solution

Intervention Hierarchy (Ancestors)

Fentanyl; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Martin Angst, MD, Professor, Dept. of Anesthesia, Stanford SOM
• Organization: Stanford School of Medicine

ang@stanford.edu

650-498-5109

Study Officials

• Martin S Angst

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Anesthesia

Study Record Dates

• First Submitted: March 2, 2010
• First Posted: March 29, 2010
• Study Start: January 1, 2010
• Primary Completion: June 1, 2010
• Study Completion: August 1, 2010
• Last Updated: February 24, 2017
• Results First Posted: February 24, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)