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NCT Number: NCT01222091

Study on the Effect of a Beta Blocker on Increased Sensitivity to Pain in Humans Caused by Opioids

This research study explores whether a beta-blocker (propranolol) can prevent a person from becoming more sensitive to pain after administration of an opioid (remifentanil). Beta blockers inhibit the sympathetic (fight or flight) response and are often used to treat angina and high blood pressure. In a previous study in human volunteers, the investigators demonstrated an increased sensitivity to pain after a 60-minute infusion of the opioid remifentanil. The goal of this study is to identify a possible inhibitor of this phenomenon.

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Key information

Conditions

Hyperalgesia Nervous System Diseases Neurologic Manifestations Pathological Conditions, Signs and Symptoms Sensation Disorders Signs and Symptoms Somatosensory Disorders

Age range

18 year–45 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2

Primary location

Stanford University School of Medicine

Stanford, California, 94305, United States

About this study

Recent evidence suggests that opioid therapy may cause a biphasic response, i.e. initial pain relief followed paradoxically by a longer lasting hypersensitivity to pain. Recent genetic analysis in mice suggests that beta adrenergic receptor antagonists reduce opiate-induced hyperalgesia (OIH). The purpose of this study is to determine the analgesic and antihyperalgesic properties of the beta-blocker propranolol on remifentanil-induced hypersensitivity in humans.

The investigators want to determine the analgesic and antihyperalgesic properties of the beta-blocker propranolol on remifentanil-induced hypersensitivity in humans. The investigators hope to learn whether the administration of beta-blocker propranolol will significantly diminish the hyperalgesic response after administration of an opioid.

The primary outcome measure for this study is change in size (area) of secondary hyperalgesia after cessation of remifentanil infusion, a measure of OIH.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Healthy men,
  • Age between 18 and 45 years
  • Normal weight (according to the table provided by Metropolitan Life Insurance).

Exclusion criteria

  • Hypersensitivity to opioids or naloxone,
  • History of addictive disease,
  • Significant cardiac, respiratory, gastrointestinal, neurological, dermatological, and psychiatric diseases,
  • Concurrent medication with an analgesic drug,
  • Student and employees affiliated with our laboratory

Treatment and study plan

Propranolol

Drug

Propranolol administered intravenously, initially set to target plasma concentration of 5 ng/mL, titrated upward in 5 ng/mL intervals until a final concentration of 15 ng/mL is achieved.

Other names: Hemangeol, Inderal, Innopran

Placebo to Match Propranolol

Drug

Remifentanil

Drug

Remifentanil administered intravenously at a plasma concentration of 3 ng/mL.

Primary outcomes

  1. Percent Change From Baseline in Size (Area) of Secondary Hyperalgesia After Cessation of Remifentanil Infusion, a Measure of Opioid-induced Hyperalgesia (OIH).

    Time frame: Baseline; 15 min post remifentanil (REM) infusion; 60 min post REM infusion

    A slightly modified version of a previously described model of secondary hyperalgesia was used. Two copper wires contained in a microdialysis catheter were inserted in parallel over a length of 5 mm into the dermis of the right volar forearm. The wires were connected to a constant current stimulator controlled by a pulse generator to deliver rectangular and monophasic pulses with a duration of 0.5 mg at 2 Hz. Over a period of 15 min, the current was increased by targeting a pain rating of 5 on an 11-point numeric rating scale (0 = no pain and 10 = maximum tolerable pain) until the hyperalgesic area surrounding the stimulation site was fully established. Once the area was established, the current was held constant. Percent change from baseline in size (area) of secondary hyperalgesia after cessation of remifentanil infusion was calculated per group.

Secondary outcomes

  1. Objective Opioid Withdrawal Scale (OOWS)

    Time frame: Pretreatment [90 min prior to 60-min REM infusion]; 30 min prior to 60-min REM infusion; 15 and 40 min after start of 60-min REM infusion; 5, 15, and 75 minutes after finish of 60-min REM infusion)

    OOWS: Is a 13-item instrument of documenting physically observable signs of withdrawal, which are rated as present (1) or absent (0) during the observation period. Maximum score = 13, minimum score = 0. Lower scores correspond to fewer symptoms.

Sponsors and collaborators

Lead sponsor

Stanford University

Other

Registry information

Official study title

Effect of Beta Blockade on Opioid-Induced Hyperalgesia in Humans

Important dates

Study start
2009
Primary completion
2011
Study completion
2011
First posted
Oct 18, 2010
Registry last updated
Jun 15, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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