Fabry DiseaseCATALYSTNCT04189601
Complement Activation in the Lysosomal Storage Disorders
An observational study of Fabry Disease and Gaucher Disease, run by Melbourne Health at 1 site in Australia.
Trial summary
The lysosomal storage disorders (LSDs) are monogenic disorders associated with inflammation affecting multiple organs, and early death. Few treatments are available that can modify the disease course, and there is an urgent need to identify new steps in pathogenesis that can be targeted therapeutically. Read more about this study
- Who is it for?
- Ages 17 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Fabry Disease, Gaucher Disease, Niemann-Pick Disease, Type C
- What is being tested?
- Complement measurements
- How many people
- 0 participants
- Where
- 1 siteAustralia
- Study dates
- 30 Sep 2020to 30 Apr 2021
- 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 17 to 70 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Consenting patients with FD, GD or NPC, and age and sex-matched controls
Who may be able to join
- All consenting patients with a prior diagnosis of FD, GD or NPC will be included in the study. Control participants will be healthy volunteers.
Who cannot join
- Patients who are unable to provide consent or to perform a blood or urine test will be excluded.
Trial locations and contacts
1 site in 1 country.
About this study
The lysosomal storage disorders (LSDs) are monogenic disorders associated with inflammation affecting multiple organs, and early death. Few treatments are available that can modify the disease course, and there is an urgent need to identify new steps in pathogenesis that can be targeted therapeutically. The complement system is novel and highly plausible as a primary driver of inflammation and cellular injury in the LSDs. This study assesses the complement activation state in patients with Fabry disease (FD), Gaucher disease (GD) and Niemann-Pick disease, type C (NPC), with comparison to healthy controls. This has the potential for immense clinical benefit through targeted complement inhibition across the full spectrum of lysosomal storage disorders, in which key pathophysiological processes including the inflammatory response to lysosomally 'stored' materials are shared.
Read the detailed description
This is a single-centre, cross-sectional observational study in patients >16 years of age diagnosed with FD, GD or NPC. The research hypotheses of this study are:
- That complement is excessively activated, including at the specifically complement C5 level, in patients with the lysosomal storage disorders FD, GD and NPC.
- That complement activation drives tissue injury in the LSDs via downstream effector mechanisms including membrane attach complex (MAC/C5b-9)-mediated cytotoxicity and C5aR-mediated inflammation.
The study aims to show enhanced complement activation, including at the C5 level, in patients with FD, GD and NPC compared to healthy controls.
The research assays for this study include the primary outcome measure of plasma soluble C5b-9 (sC6b-9) levels measured using ELISA. This assay measures the degree to which ongoing C5 activation Is occurring in vivo based on sensitive detection in plasma of the key activation product C5b-9. The assay would be expected to show elevated plasma sC5b-9 levels in patients with the glycosphingolipidoses compared to disease-free controls, as was previously demonstrated in patient cohorts of atypical haemolytic uraemia syndrome (aHUS) and C3 glomerulopathy (C3G). Additional complement activation products will be assessed as secondary endpoints including plasma C3a and C5a levels by ELISA, and intracellular leukocyte C5a concentration as a marker of systemic C5a generation and C5aR1 expression.
- Being tested
- Complement measurements
- Keywords
- complement
- Medical subject headings
- Fabry Disease, Gaucher Disease, Niemann-Pick Disease, Type C, Lysosomal Storage Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Complement measurementsDiagnostic test
Blood and urine tests to assess the complement activation state
| Study group | Role | What they receive |
|---|---|---|
| Study subjects | Patients with Fabry disease, Gaucher disease, or Niemann-Pick disease, type D Receives: Diagnostic Test: Complement measurements | |
| Controls | Age- and sex-matched to Study subjects Receives: Diagnostic Test: Complement measurements |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in soluble C5b-9
Difference in sC5b-9 between Subjects and Controls at a single timepoint up to 8 months
Measured: At baseline
Secondary outcomes (1)
Other complement biomarkers
Serum C3a and C5a
Measured: Difference in C3a and C5a between Subjects and Controls at a single timepoint up to 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2019
- Study start30 Sep 2020 (estimated)
- Primary completion26 Feb 2021 (estimated)
- Study completion30 Apr 2021 (estimated)
Why it stopped: Principal Investigator Dr. Thomas Barbour passed away.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fabry DiseaseStudies 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
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Melbourne Health
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi
- Responsible party
- Sponsor
- Investigators
- Thomas D Barbour, MBBS, Principal investigator, Melbourne Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04189601
- Sponsor's protocol ID
- Royal_Melbourne
- Acronym
- CATALYST
- Status last verified
- May 2021
- First submitted
- 1 Dec 2019
- Last updated
- 7 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No IPD sharing
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Complement Activation in the Lysosomal Storage Disorders
- ClinicalTrials.gov ID
- NCT04189601
- Acronym / sponsor ID
- CATALYST / Royal_Melbourne
- Keywords
- complement
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: Principal Investigator Dr. Thomas Barbour passed away.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Melbourne HealthUniversity, hospital or other
- Collaborators
- Sanofi
- Study start
- 30 Sep 2020 (estimated)
- Primary completion
- 26 Feb 2021 (estimated)
- Study completion
- 30 Apr 2021 (estimated)
- First posted
- 6 Dec 2019 (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.
The lysosomal storage disorders (LSDs) are monogenic disorders associated with inflammation affecting multiple organs, and early death. Few treatments are available that can modify the disease course, and there is an urgent need to identify new steps in pathogenesis that can be targeted therapeutically. The complement system is novel and highly plausible as a primary driver of inflammation and cellular injury in the LSDs. This study assesses the complement activation state in patients with Fabry disease (FD), Gaucher disease (GD) and Niemann-Pick disease, type C (NPC), with comparison to healthy controls. This has the potential for immense clinical benefit through targeted complement inhibition across the full spectrum of lysosomal storage disorders, in which key pathophysiological processes including the inflammatory response to lysosomally 'stored' materials are shared.
Detailed description
This is a single-centre, cross-sectional observational study in patients >16 years of age diagnosed with FD, GD or NPC. The research hypotheses of this study are:
- That complement is excessively activated, including at the specifically complement C5 level, in patients with the lysosomal storage disorders FD, GD and NPC.
- That complement activation drives tissue injury in the LSDs via downstream effector mechanisms including membrane attach complex (MAC/C5b-9)-mediated cytotoxicity and C5aR-mediated inflammation.
The study aims to show enhanced complement activation, including at the C5 level, in patients with FD, GD and NPC compared to healthy controls.
The research assays for this study include the primary outcome measure of plasma soluble C5b-9 (sC6b-9) levels measured using ELISA. This assay measures the degree to which ongoing C5 activation Is occurring in vivo based on sensitive detection in plasma of the key activation product C5b-9. The assay would be expected to show elevated plasma sC5b-9 levels in patients with the glycosphingolipidoses compared to disease-free controls, as was previously demonstrated in patient cohorts of atypical haemolytic uraemia syndrome (aHUS) and C3 glomerulopathy (C3G). Additional complement activation products will be assessed as secondary endpoints including plasma C3a and C5a levels by ELISA, and intracellular leukocyte C5a concentration as a marker of systemic C5a generation and C5aR1 expression.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study subjects | – | Diagnostic Test: Complement measurementsPatients with Fabry disease, Gaucher disease, or Niemann-Pick disease, type D |
| Controls | – | Diagnostic Test: Complement measurementsAge- and sex-matched to Study subjects |
Who may qualify
- Ages
- 17 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Consenting patients with FD, GD or NPC, and age and sex-matched controls
Key inclusion criteria (1 listed)
- All consenting patients with a prior diagnosis of FD, GD or NPC will be included in the study. Control participants will be healthy volunteers.
Key exclusion criteria (1 listed)
- Patients who are unable to provide consent or to perform a blood or urine test will be excluded.
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 |
|---|---|---|
| Complement measurementsBlood and urine tests to assess the complement activation state | Diagnostic test | Controls, Study subjects |
Primary outcome
Change in soluble C5b-9
Time frame: At baseline
Difference in sC5b-9 between Subjects and Controls at a single timepoint up to 8 months
1 secondary outcome
Other complement biomarkers
Time frame: Difference in C3a and C5a between Subjects and Controls at a single timepoint up to 8 months
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 Jun 2021.
- Individual participant dataSharing planned: No. No IPD sharing
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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.
Thomas D Barbour, MBBS principal investigator
Melbourne Health
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 Fabry Disease and Gaucher Disease, run by Melbourne Health at 1 site in Australia.
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 1 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: withdrawn, as of the sponsor's last update on 7 Jun 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 Australia. 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?
Change in soluble C5b-9 (time frame: At baseline). 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 Jun 2021.