Study to Assess Dopamine Receptor Modulation With Rotigotine to Enhance Morphine Analgesia in the Dental Model

A Double-Blind, Placebo-Controlled, Randomized, Parallel Group Study to Assess Dopamine Receptor Modulation With Rotigotine to Enhance Opioid Analgesia Using the Oral Surgery Model of Acute Pain in Healthy Volunteers

Narcotics are widely used as the mainstay of pain treatment, although increasing doses are required over time as the individual becomes tolerant to their effects. This can lead to the development of dependence and abuse of these drugs. Research has identified a new way to decrease the risk of developing tolerance to narcotics, by giving at the same time a drug called rotigotine ("Neupro"). Rotigotine interferes with the body's chemical dopamine and is FDA-approved for the management of Parkinson's Disease.

The purpose of this research study is to look at side effects and pain control in healthy people after removal of wisdom teeth, which usually causes pain. It is thought that by giving the study drug rotigotine with the narcotic pain reliever, there will be pain control that will extend longer than when giving the narcotic alone.

Study Overview

• Status: Unknown
• Conditions: Post-op Pain
• Intervention / Treatment: Drug: Neupro® transdermal patch/placebo

Detailed Description

Inclusion Criteria:

• Male and female patients aged 18 and over scheduled to undergo elective oral surgery for the removal of impacted third molars
• Indicated for the removal of 3-4 third molars, at least two of which are categorized as partial-boney or full-boney impactions
• Self-report of moderate or severe pain on a categorical scale with a minimum of 5 out of 10 on the numerical rating scale following the offset of local anesthesia

Exclusion Criteria:

• History or intolerance to rotigotine
• Current or history of mental disorder or substance abuse
• Allergy or intolerance to opioids or local anesthetics
• Concurrent or recent use of agents that may confound the sedative effects of the study drug (opioids, benzodiazepines) over the previous 7 days or alcohol ingestion in the previous 24 hours
• Chronic or recent use of medications that might confound the effects of rotigotine, e.g., antihistamines, prescription or over-the-counter NSAIDs (Nonsteroidal anti-inflammatory drugs), acetaminophen, steroids, antidepressants, muscle relaxants.
• Concurrent or history of chronic diseases, e.g., diabetes, rheumatoid arthritis, liver disease, cancer, hypertension or obesity (body mass index >35).

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • School of Dental Medicine at East Carolina University
      • Contact: Raymond Dionne; Phone Number: 252-744-2108; Email: dionner@ecu.edu
      • Principal Investigator: Raymond Dionne, DDS, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• • Male and female patients aged 18 and over scheduled to undergo elective oral surgery for the removal of impacted third molars

  • Indicated for the removal of 3-4 third molars, at least two of which are categorized as partial-boney or full-boney impactions
  • Self-report of moderate or severe pain on a categorical scale with a minimum of 5 out of 10 on the numerical rating scale following the offset of local anesthesia

Exclusion Criteria:

• History or intolerance to rotigotine

  • Current or history of mental disorder or substance abuse
  • Allergy or intolerance to opioids or local anesthetics
  • Concurrent or recent use of agents that may confound the sedative effects of the study drug (opioids, benzodiazepines) over the previous 7 days or alcohol ingestion in the previous 24 hours
  • Chronic or recent use of medications that might confound the effects of rotigotine, e.g., antihistamines, prescription or over-the-counter NSAIDs, acetaminophen, steroids, antidepressants, muscle relaxants.
  • Concurrent or history of chronic diseases, e.g., diabetes, rheumatoid arthritis, liver disease, cancer, hypertension or obesity (body mass index >35).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo patch; Neupro® transdermal patch/placebo randomly allocated like a flip of a coin applied to your skin at the dose of 8 mg/day or a matching placebo patch after the oral surgery procedure is completed.	Drug: Neupro® transdermal patch/placebo; 8mg transdermal patch Neupro® transdermal patch/placebo; Other Names: also known as rotigotine
Experimental: Neupro® transdermal patch; Neupro® transdermal patch/placebo randomly allocated like a flip of a coin applied to your skin at the dose of 8 mg/day or a matching placebo patch after the oral surgery procedure is completed.	Drug: Neupro® transdermal patch/placebo; 8mg transdermal patch Neupro® transdermal patch/placebo; Other Names: also known as rotigotine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sum of pain intensity difference scores	The primary outcome measure will be the SPID (sum of pain intensity difference scores) over the 3-hour observation period for MS(morphine sulfate)+Nuepro versus MS.	up to six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analgesic tablets taken postoperatively	The number of analgesic tablets taken over the first 48 hours postoperatively will be compared between the two groups as a secondary measure of the ability of the D3 agonist to potentiate opioid analgesia as a surrogate indicator of reduced potential for tolerance development.	December 2014

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
assess pain	assess the translational potential of what has been demonstrated in the lab to human subjects experiencing painful conditions that require control with morphine. We hope to provide proof of concept for a treatment strategy that will allow opiates to maintain their effectiveness at low doses without the emergence of tolerance and other side effects, even with prolonged use.	up 48 hours

Collaborators and Investigators

• Sponsor: East Carolina University
• Investigators: Principal Investigator: Raymond Dionne, DDS, PhD, School of Dental Medicine, East Carolina University

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Anticipated): November 1, 2016
• Study Completion (Anticipated): January 1, 2017

Study Registration Dates

• First Submitted: April 14, 2014
• First Submitted That Met QC Criteria: April 24, 2014
• First Posted (Estimate): April 28, 2014

Study Record Updates

• Last Update Posted (Estimate): August 7, 2015
• Last Update Submitted That Met QC Criteria: August 6, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agonists; Dopamine Agents; Rotigotine
• Other Study ID Numbers: 14-000723; 112101 668916 (Other Identifier: East Carolina University)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No