Sickle Cell DiseasePhase 4NCT00513864
Assessment of Opioid Analgesia in Sickle Cell
A Phase 4 study testing Dextromethorphan, Codeine and Morphine in people with Sickle Cell Disease, run by Children's National Research Institute at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 7 to 18 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Dextromethorphan, Codeine and Morphine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2006to Mar 2012
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: 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.
Read the 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.
- Conditions
- Sickle Cell Disease
- Being tested
- Dextromethorphan, Codeine, Morphine
- Keywords
- Opioid Analgesics, Morphine, Codeine, Sickle Cell Disease
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DextromethorphanDrug
Also called (+)-3-methoxy-17-methyl-9α,13α,14α-morphinan, DXM
one time dose - 0.3mg/kg PO
CodeineDrug
Also called 3-methylmorphine
one time dose - 2mg/kg PO
MorphineDrug
Also called MS Contin, MSIR
one time dose - 0.15mg/kg IV
| Study group | Role | What they receive |
|---|---|---|
| CYP2D6- | Active comparator | This arm consists of subjects that are poor metabolizers (PM) and intermediate metabolizers (IM). Receives: Drug: Dextromethorphan; Drug: Codeine; Drug: Morphine |
| CYP2D6+ | Active comparator | Extensive metabolizers (EM) of codeine Receives: Drug: Dextromethorphan; Drug: Codeine; Drug: Morphine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain Tolerance Threshold
5 measurements over 8 hours; 2 separate days
Measured: 5 seconds
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2007 (estimated)
- Study startNov 2006
- Primary completionMar 2012
- Study completionMar 2012
Why it stopped: lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by Children's National Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's National Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Julia Finkel, Children's National Research Institute
- Investigators
- Julia C. Finkel, M.D., Principal investigator, Children's National Medical Center-PPRU
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00513864
- Sponsor's protocol ID
- 3919
- Status last verified
- Dec 2014
- First submitted
- 8 Aug 2007
- Last updated
- 23 Dec 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-Invasive Assessment of Opioid Analgesia in Children With Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT00513864
- Acronym / sponsor ID
- 3919
- Conditions
- Sickle Cell Disease
- Keywords
- Opioid Analgesics, Morphine, Codeine, Sickle Cell Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Children's National Research InstituteUniversity, hospital or other
- Study start
- Nov 2006
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 9 Aug 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CYP2D6- | Active comparator | Drug: Dextromethorphan, Drug: Codeine, Drug: MorphineThis arm consists of subjects that are poor metabolizers (PM) and intermediate metabolizers (IM). |
| CYP2D6+ | Active comparator | Drug: Dextromethorphan, Drug: Codeine, Drug: MorphineExtensive metabolizers (EM) of codeine |
Who may qualify
- Ages
- 7 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DextromethorphanAlso: (+)-3-methoxy-17-methyl-9α,13α,14α-morphinan, DXMone time dose - 0.3mg/kg PO | Drug | CYP2D6+, CYP2D6- |
| CodeineAlso: 3-methylmorphineone time dose - 2mg/kg PO | Drug | CYP2D6+, CYP2D6- |
| MorphineAlso: MS Contin, MSIRone time dose - 0.15mg/kg IV | Drug | CYP2D6+, CYP2D6- |
Primary outcome
Pain Tolerance Threshold
Time frame: 5 seconds
5 measurements over 8 hours; 2 separate days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julia C. Finkel, M.D. principal investigator
Children's National Medical Center-PPRU
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dextromethorphan, Codeine and Morphine in people with Sickle Cell Disease, run by Children's National Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 23 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain Tolerance Threshold (time frame: 5 seconds). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2014.