Assessment of Opioid Analgesia in Sickle Cell

December 19, 2014 updated by: Julia Finkel, Children's National Research Institute

Non-Invasive Assessment of Opioid Analgesia in Children With Sickle Cell Disease

To develop and validate a non-invasive, in vivo, phenotyping method for CYP2D6 using the non-injurious neuroselective electrical stimulation technique: pain perception threshold/pain tolerance threshold (PPT/PTT) in children and adolescents with sickle cell disease.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Codeine is a pro-drug with its analgesic activity being dependent on the metabolism of codeine to morphine. The metabolism of codeine to morphine is catalyzed by the cytochrome P450 enzyme 2D6 (CYP2D6) of which there are over 70 genetic variants leading to differing metabolic capabilities within populations. It is hypothesized that the changes in PPT/PTT will vary based on the individuals ability to convert morphine to codeine.

Ineffective analgesic management of patients with sickle cell disease remains a major problem in the management of the disorder in both adults and children. The pharmacological treatment of acute and chronic pain conditions resulting from vaso-occlusive crises in children with sickle cell disease typically involves the use of opioids. In the outpatient setting, this is most commonly achieved with administration of codeine and/or tramadol, both substrates of cytochrome P450 2D6 (CYP2D6). Currently these drugs are used in this patient population without any information concerning the patient's capacity to metabolize these CYP2D6 substrates which may lead to over and under treatment of pain depending on their CYP2D6 activity. The proposed objectives in this application will address this issue by the development of a pharmacodynamic assessment tool that will objectively assess the response to morphine in terms of analgesic response (pharmacodynamic assessment). This new tool might also serve as a non-invasive technique for CYP2D6 phenotyping if CYP2D6 substrates are used for pain therapy by assessing specifically morphine response. Development of this novel assessment tool will result in improved opioid analgesic therapy in this population. Future anticipated studies will examine the application of this technique in the determination of opioid tolerance and hyperalgesia.

Study Type

Interventional

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's National Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

7 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • The subject is 7 to 18 years of age
  • The subject is of African American descent
  • The subject has sickle cell disease (HbSS)
  • The subject has a history of vaso-occlusive crisis occurring within the 6 months prior to enrollment requiring opioid analgesia use
  • The subject is willing to remain at the research site for the duration of each study session.
  • The subject's parent / legal guardian has provided written informed consent to study participation
  • The subject has provided written assent to study participation

Exclusion Criteria:

  • The subject is a pregnant or lactation female (if post-menarchal, a negative pregnancy test must be confirmed on the day that any drug is administered (i.e., morphine, dextromethorphan or codeine)
  • The subject has a history of smoking
  • The subject has a history of alcohol use within the last 24 hours prior to testing session(s)
  • The subject has a medical history of neuropathic pain, gastrointestinal, hepatic or renal disease
  • The subject has a history of medication use including herbal therapies that are known to inhibit or induce CYP2D6 or morphine
  • The subject has known or suspected hypersensitivities / allergies to codeine, morphine or dextromethorphan
  • The subject is in active, vaso-occlusive crisis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: CYP2D6-
This arm consists of subjects that are poor metabolizers (PM) and intermediate metabolizers (IM).
Drug: Dextromethorphan
one time dose - 0.3mg/kg PO
Other Names:
  • DXM
  • (+)-3-methoxy-17-methyl-9α,13α,14α-morphinan
Drug: Codeine
one time dose - 2mg/kg PO
Other Names:
  • 3-methylmorphine
Drug: Morphine
one time dose - 0.15mg/kg IV
Other Names:
  • MS Contin
  • MSIR
Active Comparator: CYP2D6+
Extensive metabolizers (EM) of codeine
Drug: Dextromethorphan
one time dose - 0.3mg/kg PO
Other Names:
  • DXM
  • (+)-3-methoxy-17-methyl-9α,13α,14α-morphinan
Drug: Codeine
one time dose - 2mg/kg PO
Other Names:
  • 3-methylmorphine
Drug: Morphine
one time dose - 0.15mg/kg IV
Other Names:
  • MS Contin
  • MSIR

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pain Tolerance Threshold
Time Frame: 5 seconds
5 measurements over 8 hours; 2 separate days
5 seconds

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's National Research Institute

Investigators

  • Principal Investigator: Julia C. Finkel, M.D., Children's National Medical Center-PPRU

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2006

Primary Completion (Actual)

March 1, 2012

Study Completion (Actual)

March 1, 2012

Study Registration Dates

First Submitted

August 8, 2007

First Submitted That Met QC Criteria

August 8, 2007

First Posted (Estimate)

August 9, 2007

Study Record Updates

Last Update Posted (Estimate)

December 23, 2014

Last Update Submitted That Met QC Criteria

December 19, 2014

Last Verified

December 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3919

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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