Assessment of Opioid Analgesia in Sickle Cell

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Julia Finkel, Children's Research Institute
ClinicalTrials.gov Identifier:
NCT00513864
First received: August 8, 2007
Last updated: May 1, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Sickle Cell Disease
Drug: Dextromethorphan
Drug: Codeine
Drug: Morphine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Non-Invasive Assessment of Opioid Analgesia in Children With Sickle Cell Disease

Resource links provided by NLM:


Further study details as provided by Children's Research Institute:

Primary Outcome Measures:
  • Pain Tolerance Threshold [ Time Frame: 5 seconds ] [ Designated as safety issue: No ]
    5 measurements over 8 hours; 2 separate days


Enrollment: 62
Study Start Date: November 2006
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • (+)-3-methoxy-17-methyl-9α,13α,14α-morphinan
  • DXM
Drug: Codeine
one time dose - 2mg/kg PO
Other Name: 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:
  • (+)-3-methoxy-17-methyl-9α,13α,14α-morphinan
  • DXM
Drug: Codeine
one time dose - 2mg/kg PO
Other Name: 3-methylmorphine
Drug: Morphine
one time dose - 0.15mg/kg IV
Other Names:
  • MS Contin
  • MSIR

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.

  Eligibility

Ages Eligible for Study:   7 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00513864

Locations
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
Sponsors and Collaborators
Children's Research Institute
Investigators
Principal Investigator: Julia C. Finkel, M.D. Children's National Medical Center-PPRU
  More Information

No publications provided

Responsible Party: Julia Finkel, MD, Children's Research Institute
ClinicalTrials.gov Identifier: NCT00513864     History of Changes
Other Study ID Numbers: 3919
Study First Received: August 8, 2007
Last Updated: May 1, 2012
Health Authority: United States: Federal Government

Keywords provided by Children's Research Institute:
Opioid Analgesics
Morphine
Codeine
Sickle Cell Disease

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Codeine
Morphine
Analgesics, Opioid
Dextromethorphan
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Antitussive Agents
Respiratory System Agents
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014