H SyndromeNCT06742073
Histiocytosis and Inflammatory Manifestations in Patients with H Syndrome
An observational study of H Syndrome, run by Rabin Medical Center at 1 site in Israel.
Trial summary
H syndrome is a rare genetic disorder predisposing to histiocytosis. Our knowledge of the clinical spectrum of these patients is based on case reports and small patient series. Patients with H syndrome have been treated with a range of immunomodulatory and chemotherapeutic agents, with limited success. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- H Syndrome
- How many people
- 120 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Nov 2024to 1 Aug 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Any patient with a genetically confirmed diagnosis of H syndrome (two pathogenic or likely pathogenic germline SLC29A3 variants)
Who may be able to join
None listed.
Who cannot join
- -
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Israel1 site, 1 recruiting
- Recruiting
Schneider Children's Medical Center
Petah Tikva
Sarah Elitzur, MD, 97239253766, sarhae@clalit.org.il
Naomi Litichever, PhD, 97239253705, naomilitichever@clalit.org.il
About this study
Official title: Histiocytosis and Inflammatory Manifestations in Patients with H Syndrome- a Multinational Collaboration
H syndrome is a rare genetic disorder predisposing to histiocytosis. Our knowledge of the clinical spectrum of these patients is based on case reports and small patient series. Patients with H syndrome have been treated with a range of immunomodulatory and chemotherapeutic agents, with limited success. We aim to comprehensively assess the clinical manifestations and patterns of treatment response in a multinational cohort of patients with H syndrome.
Read the detailed description
H syndrome is a rare inflammatory genetic disorder predisposing to histiocytosis, caused by germline biallelic loss-of-function mutations in SLC29A3, encoding the protein equilibrative nucleoside transporter 3 (ENT3). ENT3 transports nucleosides from lysosomes to the cytoplasm following lysosomal degradation of nucleic acids. Results from our previous study (under review) suggest a model in which impaired nucleoside trafficking aberrantly activates nucleoside-sensing Toll-like receptors, leading to persistent activation of ERK, driving histiocytosis. This constitutes a novel signaling pathway leading to activation of ERK and histiocytosis, in the absence of somatic mutations in MAPK cascade genes. Our knowledge of the heterogenous clinical spectrum of these patients is based on case reports and small patient series. Patients with H syndrome have been treated with a range of immunomodulatory and chemotherapeutic agents, with limited success. Improvement following therapy with tocilizumab, an IL6-receptor antibody, has recently been reported in isolated case reports. There is a lack of data on MEK inhibitor therapy in these patients. We aim to comprehensively assess the clinical manifestations and patterns of treatment response in a multinational cohort of patients with H syndrome.
- Conditions
- H Syndrome
- Keywords
- SLC29A3
- Medical subject headings
- Histiocytosis with joint contractures and sensorineural deafness
What is being measured
The primary outcome is the main question the study is designed to answer.
Response to therapy
complete response/partial response/stable disease/progressive disease
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2024
- Study start1 Nov 2024
- Primary completion1 Jul 2026 (estimated)
- Study completion1 Aug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for H SyndromeStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rabin Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sarah Elitzur, MD, Study director, Schneider Children'ds Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06742073
- Sponsor's protocol ID
- RMC-0230-24
- Status last verified
- Dec 2024
- First submitted
- 15 Dec 2024
- Last updated
- 19 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Histiocytosis and Inflammatory Manifestations in Patients with H Syndrome- a Multinational Collaboration
- ClinicalTrials.gov ID
- NCT06742073
- Acronym / sponsor ID
- RMC-0230-24
- Conditions
- H Syndrome
- Keywords
- SLC29A3
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Rabin Medical CenterUniversity, hospital or other
- Study start
- 1 Nov 2024 (actual)
- Primary completion
- 1 Jul 2026 (estimated)
- Study completion
- 1 Aug 2026 (estimated)
- First posted
- 19 Dec 2024 (actual)
- 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.
H syndrome is a rare genetic disorder predisposing to histiocytosis. Our knowledge of the clinical spectrum of these patients is based on case reports and small patient series. Patients with H syndrome have been treated with a range of immunomodulatory and chemotherapeutic agents, with limited success. We aim to comprehensively assess the clinical manifestations and patterns of treatment response in a multinational cohort of patients with H syndrome.
Detailed description
H syndrome is a rare inflammatory genetic disorder predisposing to histiocytosis, caused by germline biallelic loss-of-function mutations in SLC29A3, encoding the protein equilibrative nucleoside transporter 3 (ENT3). ENT3 transports nucleosides from lysosomes to the cytoplasm following lysosomal degradation of nucleic acids. Results from our previous study (under review) suggest a model in which impaired nucleoside trafficking aberrantly activates nucleoside-sensing Toll-like receptors, leading to persistent activation of ERK, driving histiocytosis. This constitutes a novel signaling pathway leading to activation of ERK and histiocytosis, in the absence of somatic mutations in MAPK cascade genes. Our knowledge of the heterogenous clinical spectrum of these patients is based on case reports and small patient series. Patients with H syndrome have been treated with a range of immunomodulatory and chemotherapeutic agents, with limited success. Improvement following therapy with tocilizumab, an IL6-receptor antibody, has recently been reported in isolated case reports. There is a lack of data on MEK inhibitor therapy in these patients. We aim to comprehensively assess the clinical manifestations and patterns of treatment response in a multinational cohort of patients with H syndrome.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Any patient with a genetically confirmed diagnosis of H syndrome (two pathogenic or likely pathogenic germline SLC29A3 variants)
Key inclusion criteria (0 listed)
Key exclusion criteria (1 listed)
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Response to therapy
Time frame: 6 months
complete response/partial response/stable disease/progressive disease
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2024.
- 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.
Sarah Elitzur, MD study director
Schneider Children'ds Medical Center
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 H Syndrome, run by Rabin Medical Center at 1 site in Israel.
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 0 inclusion and 1 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: looking for participants now, as of the sponsor's last update on 19 Dec 2024. 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 Israel. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sarah Elitzur, MD (+97239253766, sarhae@clalit.org.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response to therapy (time frame: 6 months). 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 19 Dec 2024.