Assessment of Opioid Analgesia in Sickle Cell

Sickle Cell Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00513864
• Other study ID #: 3919
• Status: Withdrawn
• Phase: Phase 4
• First received: August 8, 2007
• Last updated: December 19, 2014
• Start date: November 2006
• Est. completion date: March 2012

Study information

• Verified date: December 2014
• Source: Children's Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 7 Years to 18 Years

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Drug:
• Dextromethorphan
one time dose - 0.3mg/kg PO
• Codeine
one time dose - 2mg/kg PO
• Morphine
one time dose - 0.15mg/kg IV

Locations

Country	Name	City	State
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Children's Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pain Tolerance Threshold	5 measurements over 8 hours; 2 separate days	5 seconds	No