Histamine BiotransformationNCT00809692
In Vivo Assessment of Histamine Pharmacodynamics
A study testing validated techniques for histamine response and new technique for histamine response in people with Histamine Biotransformation, run by Children's Mercy Hospital Kansas City at 1 site in United States.
Trial summary
A critical first step to address the "pharmacodynamic information gap" in pediatrics resides with the development of methods capable of accurately measuring the time dependent effects of xenobiotic exposure in a manner sufficient to enable an integrative analysis of drug action which incorporates both pharmacokinetic… Read more about this study
- Who is it for?
- Ages 7 to 18 years
- Conditions the study is for
- Histamine Biotransformation
- What is being tested?
- validated techniques for histamine response and new technique for histamine response
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2007to Sep 2008
- Phase
- Interventional
- 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
- Male or female between ages of 7 and 18 years
- Diagnosed with allergic disease (i.e., allergic rhinitis, allergic conjunctivitis, allergic asthma)
- Informed consent (Parental permission and subject assent)
Who cannot join
- Previous history or laboratory evidence of McCune Albright syndrome, immunodeficiency, mastocytosis, receipt of immunomodulatory treatment, chronic conditions associated with abnormalities of the integument, hepatic or renal compromise, neoplastic disease, movement or neurologic disorders and uncontrolled ADHD
- Evidence of atopic dermatitis within a 2 year period from the time of study
- History of previous anaphylactic or anaphylactoid episode
- Evidence of pregnancy (by urinary hCG) or lactation at the time of study
- Receipt of drugs (within a specified time period) of agents capable of altering the response to histamine provocation (e.g., antihistamines, systemic corticosteroids, tricyclic antidepressants)
- Presence of any condition that, in the opinion of the investigator, would produce difficulty with adherence to study procedures.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
About this study
Official title: In Vivo Functional Assessment of Histamine Pharmacodynamics in Children
A critical first step to address the "pharmacodynamic information gap" in pediatrics resides with the development of methods capable of accurately measuring the time dependent effects of xenobiotic exposure in a manner sufficient to enable an integrative analysis of drug action which incorporates both pharmacokinetic and pharmacogenetic determinants. The proposed study will evaluate laser Doppler flowimetry, a necessary initial step in developing an "ideal" pharmacodynamic surrogate endpoint that ultimately could be used in infants, children and adolescents to fully characterize the impact of development on the pharmacokinetic (PK) / pharmacodynamic (PD) / pharmacogenetic (PG) determinants of drug effect for agents capable of modulating the cellular response to histamine.
Read the detailed description
The overall goal of this research is to develop and validate non-invasive approaches suitable for use in pediatrics that are sufficient to directly evaluate genotype-phenotype associations as determinants of the concentration-effect profile of drugs capable of altering microvascular function. The specific goal of this project will be to assess whether microvascular blood flow determined by a previously validated laser Doppler technique can be used as a reliable surrogate endpoint capable of functionally discriminating the effects of polymorphisms in the genes which are quantitatively important for histamine biotransformation. The investigators hypothesize that microvascular blood flow velocity can be used as a valid surrogate marker to discriminate the functional consequences of allelic variants in the enzymes primarily responsible for the biotransformation of histamine.
The project includes two parts:
- Validation of histamine iontophoresis (with measurement of microvascular blood flow by laser Doppler flowimetry) in a pediatric cohort as a pharmacologic provocation test capable of reliably characterizing the normal physiologic response of the cutaneous microvasculature to this xenobiotic addressed by a study in 50 children with a diagnosis of allergic disease or other "allergic" conditions where treatment with antihistamines represents the medical "standard of care". Subjects will concomitantly (on contralateral extremities) receive histamine challenges by the "gold standard" cutaneous prick test (time dependent response assessed by serial assessment of wheal and flare reactions) and by a previously described iontophoresis technique (time dependent response by serial assessment of microvascular blood flow using a validated laser Doppler technique).Additionally, DNA will be isolated from these subjects for genotyping as described in part 2).
- Assessment of microvascular response to histamine challenge as a surrogate marker capable of functionally discriminating genotype-phenotype associations for polymorphically expressed genes that are quantitatively important in regulating the biotransformation and pharmacologic inactivation of histamine addressed first by genotyping 150 additional subjects who have an established diagnosis of allergic disease where treatment with antihistamines represents the medical "standard of care". Genotype data for candidate genes of primary interest, histamine-N-methyltransferase (HNMT) and diamine oxidase (DAO), will thus be available from a total of 200 subjects. Based upon known genotype-phenotype associations for HNMT (the enzyme primarily responsible for histamine biotransformation), two cohorts of subjects will be selected from those studied using an extreme discordant phenotype approach: subjects predicted, based upon genotype, to have reduced HMNT activity (i.e., those with 1 or 0 functional alleles) and subjects predicted to have normal enzyme activity (i.e., those with two functional alleles). These study participants will then receive a transcutaneous histamine challenge delivered by iontophoresis, followed by repeated assessment of microvascular reactivity reflected by time-averaged measurement of blood flow velocity using an established laser Doppler technique. Statistical analysis of blood flow velocity and other parameters from the laser Doppler assessment will be used as the primary outcome measurement for comparison of the two study cohorts with respect to expression of HNMT and DAO and the functional consequences thereof, using histamine response as the surrogate assessment of phenotype.
- Conditions
- Histamine Biotransformation
- Being tested
- validated techniques for histamine response, new technique for histamine response
- Keywords
- histamine biotransformation, laser Doppler flowimetry, pediatric pharmacology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
validated techniques for histamine responseProcedure or surgery
the prick test and iontophoresis technique (serial assessment of blood flow using validated Doppler technique)
new technique for histamine responseProcedure or surgery
laser Dopper technique and genotyping
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | 50 subjects with allergic disease receiving histamine challenges by the prick test and iontophoresis technique (serial assessment of blood flow using validated Doppler technique) Receives: Procedure: validated techniques for histamine response |
| 2 | Experimental | 150 additional subjects with allergic disease; undergo genotyping; laser Dopper assessment Receives: Procedure: new technique for histamine response |
What is being measured
The primary outcome is the main question the study is designed to answer.
Statistical analysis of blood flow velocity and other parameters from the laser Doppler assessment
Measured: 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2008 (estimated)
- Study startSep 2007
- Primary completionMay 2008
- Study completionSep 2008
Why it stopped: Study withdrawn and combined with a new protocol
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Histamine BiotransformationStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Mercy Hospital Kansas City
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Bridgette L. Jones, MD, Principal investigator, Children's Mercy Hospital and Clinics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00809692
- Sponsor's protocol ID
- 10898
- Status last verified
- Jan 2021
- First submitted
- 15 Dec 2008
- Last updated
- 7 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- In Vivo Functional Assessment of Histamine Pharmacodynamics in Children
- ClinicalTrials.gov ID
- NCT00809692
- Acronym / sponsor ID
- 10898
- Conditions
- Histamine Biotransformation
- Keywords
- histamine biotransformation, laser Doppler flowimetry, pediatric pharmacology
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study withdrawn and combined with a new protocol
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Children's Mercy Hospital Kansas CityUniversity, hospital or other
- Study start
- Sep 2007 (actual)
- Primary completion
- May 2008 (actual)
- Study completion
- Sep 2008 (actual)
- First posted
- 17 Dec 2008 (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.
A critical first step to address the "pharmacodynamic information gap" in pediatrics resides with the development of methods capable of accurately measuring the time dependent effects of xenobiotic exposure in a manner sufficient to enable an integrative analysis of drug action which incorporates both pharmacokinetic and pharmacogenetic determinants. The proposed study will evaluate laser Doppler flowimetry, a necessary initial step in developing an "ideal" pharmacodynamic surrogate endpoint that ultimately could be used in infants, children and adolescents to fully characterize the impact of development on the pharmacokinetic (PK) / pharmacodynamic (PD) / pharmacogenetic (PG) determinants of drug effect for agents capable of modulating the cellular response to histamine.
Detailed description
The overall goal of this research is to develop and validate non-invasive approaches suitable for use in pediatrics that are sufficient to directly evaluate genotype-phenotype associations as determinants of the concentration-effect profile of drugs capable of altering microvascular function. The specific goal of this project will be to assess whether microvascular blood flow determined by a previously validated laser Doppler technique can be used as a reliable surrogate endpoint capable of functionally discriminating the effects of polymorphisms in the genes which are quantitatively important for histamine biotransformation. The investigators hypothesize that microvascular blood flow velocity can be used as a valid surrogate marker to discriminate the functional consequences of allelic variants in the enzymes primarily responsible for the biotransformation of histamine.
The project includes two parts:
- Validation of histamine iontophoresis (with measurement of microvascular blood flow by laser Doppler flowimetry) in a pediatric cohort as a pharmacologic provocation test capable of reliably characterizing the normal physiologic response of the cutaneous microvasculature to this xenobiotic addressed by a study in 50 children with a diagnosis of allergic disease or other "allergic" conditions where treatment with antihistamines represents the medical "standard of care". Subjects will concomitantly (on contralateral extremities) receive histamine challenges by the "gold standard" cutaneous prick test (time dependent response assessed by serial assessment of wheal and flare reactions) and by a previously described iontophoresis technique (time dependent response by serial assessment of microvascular blood flow using a validated laser Doppler technique).Additionally, DNA will be isolated from these subjects for genotyping as described in part 2).
- Assessment of microvascular response to histamine challenge as a surrogate marker capable of functionally discriminating genotype-phenotype associations for polymorphically expressed genes that are quantitatively important in regulating the biotransformation and pharmacologic inactivation of histamine addressed first by genotyping 150 additional subjects who have an established diagnosis of allergic disease where treatment with antihistamines represents the medical "standard of care". Genotype data for candidate genes of primary interest, histamine-N-methyltransferase (HNMT) and diamine oxidase (DAO), will thus be available from a total of 200 subjects. Based upon known genotype-phenotype associations for HNMT (the enzyme primarily responsible for histamine biotransformation), two cohorts of subjects will be selected from those studied using an extreme discordant phenotype approach: subjects predicted, based upon genotype, to have reduced HMNT activity (i.e., those with 1 or 0 functional alleles) and subjects predicted to have normal enzyme activity (i.e., those with two functional alleles). These study participants will then receive a transcutaneous histamine challenge delivered by iontophoresis, followed by repeated assessment of microvascular reactivity reflected by time-averaged measurement of blood flow velocity using an established laser Doppler technique. Statistical analysis of blood flow velocity and other parameters from the laser Doppler assessment will be used as the primary outcome measurement for comparison of the two study cohorts with respect to expression of HNMT and DAO and the functional consequences thereof, using histamine response as the surrogate assessment of phenotype.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Procedure: validated techniques for histamine response50 subjects with allergic disease receiving histamine challenges by the prick test and iontophoresis technique (serial assessment of blood flow using validated Doppler technique) |
| 2 | Experimental | Procedure: new technique for histamine response150 additional subjects with allergic disease; undergo genotyping; laser Dopper assessment |
Who may qualify
- Ages
- 7 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Male or female between ages of 7 and 18 years
- Diagnosed with allergic disease (i.e., allergic rhinitis, allergic conjunctivitis, allergic asthma)
- Informed consent (Parental permission and subject assent)
Key exclusion criteria (6 listed)
- Previous history or laboratory evidence of McCune Albright syndrome, immunodeficiency, mastocytosis, receipt of immunomodulatory treatment, chronic conditions associated with abnormalities of the integument, hepatic or renal compromise, neoplastic disease, movement or neurologic disorders and uncontrolled ADHD
- Evidence of atopic dermatitis within a 2 year period from the time of study
- History of previous anaphylactic or anaphylactoid episode
- Evidence of pregnancy (by urinary hCG) or lactation at the time of study
- Receipt of drugs (within a specified time period) of agents capable of altering the response to histamine provocation (e.g., antihistamines, systemic corticosteroids, tricyclic antidepressants)
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 |
|---|---|---|
| validated techniques for histamine responsethe prick test and iontophoresis technique (serial assessment of blood flow using validated Doppler technique) | Procedure or surgery | 1 |
| new technique for histamine responselaser Dopper technique and genotyping | Procedure or surgery | 2 |
Primary outcome
Statistical analysis of blood flow velocity and other parameters from the laser Doppler assessment
Time frame: 0
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 7 Jan 2021.
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.
Bridgette L. Jones, MD principal investigator
Children's Mercy Hospital and Clinics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing validated techniques for histamine response and new technique for histamine response in people with Histamine Biotransformation, run by Children's Mercy Hospital Kansas City 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 3 inclusion and 6 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 7 Jan 2021. 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.
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?
Statistical analysis of blood flow velocity and other parameters from the laser Doppler assessment (time frame: 0). 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 7 Jan 2021.