Assessment of Opioid Analgesia in Sickle Cell

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00513864
Recruitment Status : Withdrawn (lack of funding)
First Posted : August 9, 2007
Last Update Posted : December 23, 2014
Information provided by (Responsible Party):
Julia Finkel, Children's Research Institute

Brief Summary:
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 or disease Intervention/treatment Phase
Sickle Cell Disease Drug: Dextromethorphan Drug: Codeine Drug: Morphine Phase 4

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  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Non-Invasive Assessment of Opioid Analgesia in Children With Sickle Cell Disease
Study Start Date : November 2006
Actual Primary Completion Date : March 2012
Actual Study Completion Date : March 2012

Resource links provided by the National Library of Medicine

Drug Information available for: Codeine

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:
  • (+)-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

Primary Outcome Measures :
  1. Pain Tolerance Threshold [ Time Frame: 5 seconds ]
    5 measurements over 8 hours; 2 separate days

Information from the National Library of Medicine

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Ages Eligible for Study:   7 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00513864

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

Responsible Party: Julia Finkel, MD, Children's Research Institute Identifier: NCT00513864     History of Changes
Other Study ID Numbers: 3919
First Posted: August 9, 2007    Key Record Dates
Last Update Posted: December 23, 2014
Last Verified: December 2014

Keywords provided by Julia Finkel, Children's Research Institute:
Opioid Analgesics
Sickle Cell Disease

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