Urticaria PigmentosaNCT02761473
Cutaneous Mastocytosis in Children: Analysis of Somatic and Germline Mutations
An observational study of Urticaria Pigmentosa and Cutaneous Mastocytosis, run by University of Minnesota at 1 site in United States.
Trial summary
Pediatric mastocytosis is an orphan disease, which encompasses several clinically distinct entities including solitary mastocytoma, urticaria pigmentosa, diffuse cutaneous mastocytosis and the newly recognized mast cell activation syndrome. Read more about this study
- Who is it for?
- Ages 3 months to 23 yearsHealthy volunteers can take part
- Conditions the study is for
- Urticaria Pigmentosa, Cutaneous Mastocytosis
- What is being tested?
- skin biopsy and blood draw
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2016to 1 May 2020
- Phase
- Observational
- 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 3 months to 23 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: Patients with urticaria pigmentosa and first degree relatives
Who may be able to join
- Affected subject:
- Subjects will be eligible to participate in the study if all of the following conditions exist:
- Clinical diagnosis of urticaria pigmentosa/cutaneous mastocytosis with representative skin lesions
- Age <23 years
- Capable of giving consent if 18 or older
- Over 16 years of age
Show all 10Show fewer
- Biologic parent to affected subject
- Capable of providing consent
- 1. Biologic sibling to affected subject 2. Capable of giving consent if 18 or older
- -
Who cannot join
- Absence of skin findings representative of classic urticaria pigmentosa
- Patients with primarily systemic mastocytosis
- Unable or unwilling to participate in study procedures
- 1. Unable or unwilling to participate in study procedures
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Pediatric mastocytosis is an orphan disease, which encompasses several clinically distinct entities including solitary mastocytoma, urticaria pigmentosa, diffuse cutaneous mastocytosis and the newly recognized mast cell activation syndrome. The most common form of pediatric mastocytosis is cutaneous maculopapular mastocytosis (CMPM), also known as urticaria pigmentosa (UP). There are significant knowledge gaps regarding the genetic basis of pediatric mastocytosis and the functional activity of mast cells in this condition. The Pediatric Dermatology and Pediatric Oncology services at the University of Minnesota Masonic Children's Hospital are seeing significant growth in clinical volumes of pediatric mastocytosis, including rare, familial cases. The aims of this study are to prospectively explore germline risk for UP and to perform a mutational analysis to identify somatic mutations, beyond those currently identified, in pediatric patients with UP.
Read the detailed description
Urticaria pigmentosa (UP) is a relatively common disorder in pediatric patients, and little is known regarding the somatic and germline genetic variants associated with the disease. The University of Minnesota Masonic Children's Hospital is a regional referral center for pediatric patients with mast cell disorders. Collaborators on this study include several University departments including: Pediatric Dermatology, Pediatric Oncology, the Biomedical Genomics program, Lab Medicine and Pathology department. We hypothesize that because of differences observed in the clinical behavior of pediatric- and adult-onset mast cell disease, specifically UP, we will identify novel somatic gene variants in addition to c-KIT . We further hypothesize that we will observe novel germline genetic variants in pediatric UP distinct from what has previously been described in adults.
Specific Aims include the following:
Specific Aim 1: RNA Sequencing for Gene Expression and Mutation Analysis. Utilizing RNA sequencing (RNA-Seq), we will perform paired lesional and peripheral blood sequencing in UP cases to identify variation in gene expression and define novel somatic mutations associated with pediatric UP.
Specific Aim 2: Exploration of Germline Risk. Utilizing single nucleotide polymorphism (SNP) array, we will perform linkage analysis in UP cases and their unaffected family members to identify germline genetic variants associated with UP.
- Discordant sibling analysis: Children with UP and their unaffected siblings will be compared to identify germline variants.
- Identical twin and parent analysis: Identical infant twins with a severe UP phenotype will be compared with their unaffected parents.
- Conditions
- Urticaria Pigmentosa, Cutaneous Mastocytosis
- Being tested
- skin biopsy, blood draw
- Medical subject headings
- Urticaria Pigmentosa, Mastocytosis, Cutaneous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
skin biopsyOther
A skin biopsy will be obtained from a typical UP lesion in affected patients
blood drawOther
Blood will be obtained from subjects, parents and unaffected siblings
| Study group | Role | What they receive |
|---|---|---|
| Patients with Urticaria Pigmentosa | This group will undergo skin biopsy, blood and buccal swab analyses Receives: Other: skin biopsy; Other: blood draw | |
| Family members of affected patients | This group will undergo blood and buccal swab analyses |
What is being measured
The primary outcome is the main question the study is designed to answer.
RNA sequencing
Fresh tissue from lesional skin will be obtained for gene expression and mutational analysis
Measured: 1.5 years
Secondary outcomes (1)
SNP microarray analysis
SNP microarray analysis will be performed on DNA obtained from buccal swabs or whole blood samples. Samples from patients and unaffected family members will be compared.
Measured: 1.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2016 (estimated)
- Study startNov 2016
- Primary completion1 Oct 2019
- Study completion1 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Urticaria PigmentosaStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe 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
- Observational
- Observational model
- Family based
- Time perspective
- Prospective
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02761473
- Sponsor's protocol ID
- 1608M92621
- Status last verified
- Aug 2020
- First submitted
- 15 Mar 2016
- Last updated
- 20 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Hartmann K, Escribano L, Grattan C, Brockow K, Carter MC, Alvarez-Twose I, Matito A, Broesby-Olsen S, Siebenhaar F, Lange M, Niedoszytko M, Castells M, Oude Elberink JNG, Bonadonna P, Zanotti R, Hornick JL, Torrelo A, Grabbe J, Rabenhorst A, Nedoszytko B, Butterfield JH, Gotlib J, Reiter A, Radia D, Hermine O, Sotlar K, George TI, Kristensen TK, Kluin-Nelemans HC, Yavuz S, Hagglund H, Sperr WR, Schwartz LB, Triggiani M, Maurer M, Nilsson G, Horny HP, Arock M, Orfao A, Metcalfe DD, Akin C, Valent P. Cutaneous manifestations in patients with mastocytosis: Consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology. J Allergy Clin Immunol. 2016 Jan;137(1):35-45. doi: 10.1016/j.jaci.2015.08.034. Epub 2015 Oct 21.
PubMed 26476479Longley BJ Jr, Metcalfe DD, Tharp M, Wang X, Tyrrell L, Lu SZ, Heitjan D, Ma Y. Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis. Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1609-14. doi: 10.1073/pnas.96.4.1609.
PubMed 9990072Fried AJ, Akin C. Primary mast cell disorders in children. Curr Allergy Asthma Rep. 2013 Dec;13(6):693-701. doi: 10.1007/s11882-013-0392-6.
PubMed 24150753Fett NM, Teng J, Longley BJ. Familial urticaria pigmentosa: report of a family and review of the role of KIT mutations. Am J Dermatopathol. 2013 Feb;35(1):113-6. doi: 10.1097/DAD.0b013e31826330bf.
PubMed 22892471
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cutaneous Mastocytosis in Children: Analysis of Somatic and Germline Mutations
- ClinicalTrials.gov ID
- NCT02761473
- Acronym / sponsor ID
- 1608M92621
- Conditions
- Urticaria Pigmentosa, Cutaneous Mastocytosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Study start
- Nov 2016 (actual)
- Primary completion
- 1 Oct 2019 (actual)
- Study completion
- 1 May 2020 (actual)
- First posted
- 4 May 2016 (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.
Pediatric mastocytosis is an orphan disease, which encompasses several clinically distinct entities including solitary mastocytoma, urticaria pigmentosa, diffuse cutaneous mastocytosis and the newly recognized mast cell activation syndrome. The most common form of pediatric mastocytosis is cutaneous maculopapular mastocytosis (CMPM), also known as urticaria pigmentosa (UP). There are significant knowledge gaps regarding the genetic basis of pediatric mastocytosis and the functional activity of mast cells in this condition. The Pediatric Dermatology and Pediatric Oncology services at the University of Minnesota Masonic Children's Hospital are seeing significant growth in clinical volumes of pediatric mastocytosis, including rare, familial cases. The aims of this study are to prospectively explore germline risk for UP and to perform a mutational analysis to identify somatic mutations, beyond those currently identified, in pediatric patients with UP.
Detailed description
Urticaria pigmentosa (UP) is a relatively common disorder in pediatric patients, and little is known regarding the somatic and germline genetic variants associated with the disease. The University of Minnesota Masonic Children's Hospital is a regional referral center for pediatric patients with mast cell disorders. Collaborators on this study include several University departments including: Pediatric Dermatology, Pediatric Oncology, the Biomedical Genomics program, Lab Medicine and Pathology department. We hypothesize that because of differences observed in the clinical behavior of pediatric- and adult-onset mast cell disease, specifically UP, we will identify novel somatic gene variants in addition to c-KIT . We further hypothesize that we will observe novel germline genetic variants in pediatric UP distinct from what has previously been described in adults.
Specific Aims include the following:
Specific Aim 1: RNA Sequencing for Gene Expression and Mutation Analysis. Utilizing RNA sequencing (RNA-Seq), we will perform paired lesional and peripheral blood sequencing in UP cases to identify variation in gene expression and define novel somatic mutations associated with pediatric UP.
Specific Aim 2: Exploration of Germline Risk. Utilizing single nucleotide polymorphism (SNP) array, we will perform linkage analysis in UP cases and their unaffected family members to identify germline genetic variants associated with UP.
- Discordant sibling analysis: Children with UP and their unaffected siblings will be compared to identify germline variants.
- Identical twin and parent analysis: Identical infant twins with a severe UP phenotype will be compared with their unaffected parents.
Study design
- Observational model
- Family based
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with Urticaria Pigmentosa | – | Other: skin biopsy, Other: blood drawThis group will undergo skin biopsy, blood and buccal swab analyses |
| Family members of affected patients | – | –This group will undergo blood and buccal swab analyses |
Who may qualify
- Ages
- 3 months to 23 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- Patients with urticaria pigmentosa and first degree relatives
Key inclusion criteria (10 listed)
- Subjects will be eligible to participate in the study if all of the following conditions exist:
- Clinical diagnosis of urticaria pigmentosa/cutaneous mastocytosis with representative skin lesions
- Age <23 years
- Capable of giving consent if 18 or older
- Over 16 years of age
Key exclusion criteria (4 listed)
- Absence of skin findings representative of classic urticaria pigmentosa
- Patients with primarily systemic mastocytosis
- Unable or unwilling to participate in study procedures
- 1. Unable or unwilling to participate in study procedures
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 |
|---|---|---|
| skin biopsyA skin biopsy will be obtained from a typical UP lesion in affected patients | Other | Patients with Urticaria Pigmentosa |
| blood drawBlood will be obtained from subjects, parents and unaffected siblings | Other | Patients with Urticaria Pigmentosa |
Primary outcome
RNA sequencing
Time frame: 1.5 years
Fresh tissue from lesional skin will be obtained for gene expression and mutational analysis
1 secondary outcome
SNP microarray analysis
Time frame: 1.5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2020.
- Results publication: PubMed 26476479Hartmann K, Escribano L, Grattan C, Brockow K, Carter MC, Alvarez-Twose I, Matito A, Broesby-Olsen S, Siebenhaar F, Lange M, Niedoszytko M, Castells M, Oude Elberink JNG, Bonadonna P, Zanotti R, Hornick JL, Torrelo A, Grabbe J, Rabenhorst A, Nedoszytko B, Butterfield JH, Gotlib J, Reiter A, Radia D, Hermine O, Sotlar K, George TI, Kristensen TK, Kluin-Nelemans HC, Yavuz S, Hagglund H, Sperr WR, Schwartz LB, Triggiani M, Maurer M, Nilsson G, Horny HP, Arock M, Orfao A, Metcalfe DD, Akin C, Valent P. Cutaneous manifestations in patients with mastocytosis: Consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology. J Allergy Clin Immunol. 2016 Jan;137(1):35-45. doi: 10.1016/j.jaci.2015.08.034. Epub 2015 Oct 21.
- Results publication: PubMed 9990072Longley BJ Jr, Metcalfe DD, Tharp M, Wang X, Tyrrell L, Lu SZ, Heitjan D, Ma Y. Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis. Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1609-14. doi: 10.1073/pnas.96.4.1609.
- Results publication: PubMed 24150753Fried AJ, Akin C. Primary mast cell disorders in children. Curr Allergy Asthma Rep. 2013 Dec;13(6):693-701. doi: 10.1007/s11882-013-0392-6.
- Results publication: PubMed 22892471Fett NM, Teng J, Longley BJ. Familial urticaria pigmentosa: report of a family and review of the role of KIT mutations. Am J Dermatopathol. 2013 Feb;35(1):113-6. doi: 10.1097/DAD.0b013e31826330bf.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Urticaria Pigmentosa and Cutaneous Mastocytosis, run by University of Minnesota 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 10 inclusion and 4 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: finished, as of the sponsor's last update on 20 Aug 2020. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
RNA sequencing (time frame: 1.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02761473, which also lists 4 linked publications.
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 20 Aug 2020.