Gaucher DiseaseNCT01136304
Validating a New Severity Score System for Adults With Type 1 Gaucher Disease (GD1)
An observational study of Gaucher Disease, run by University Research Foundation for Lysosomal Storage Diseases, Inc. at 2 sites in United States.
Trial summary
With the participation of an international consortium of investigators, the investigators will evaluate the validity of a new severity score system called DS3 for adult patients with Gaucher disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gaucher Disease
- What is being tested?
- Imiglucerase
- Type of treatment
- Injection or infusion
- How many people
- 173 participants
- Where
- 2 sitesUnited States
- Study dates
- Apr 2010to Dec 2013
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Consenting adult patients with type 1 Gaucher disease who are cared for at one of the participating research sites and who are enrolled in the International Collaborative Gaucher Group Gaucher Registry
Who may be able to join
- Adult patients with Type 1 Gaucher disease regardless of treatment status who are enrolled in the International Collaborative Gaucher Group (ICCG) Gaucher Registry and who are cared for at one of the participating research sites.
Who cannot join
- Children under the age of 18 years
- Patients with Type 3 Gaucher disease
- Patients who have declined to be enrolled in the ICCG Gaucher Registry
- Patients not cared for at one of the participating research sites
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Tower Cancer Research Foundation
Beverly Hills, California, 90211
Northwest Oncology Hematology Associates PA
Coral Springs, Florida, 33065
About this study
Official title: Retrospective and Prospective Validation of a Disease Severity Score System (DS3) for Adults With Type 1 Gaucher Disease (GD1)
With the participation of an international consortium of investigators, the investigators will evaluate the validity of a new severity score system called DS3 for adult patients with Gaucher disease. The investigators hypothesize that initial DS3 scores will be predictive of both disease progression and patterns of response including imiglucerase dose sensitivity and completeness and maintenance of response and that sequential DS3 scores will accurately portray either clinical progression of disease or improvement in response to treatment. The investigators will also collect DNA specimens that in future research will be used in conjunction with the DS3 scores to evaluate determinants of the clinical course and the response to treatments for Gaucher disease.
Read the detailed description
GD1 is a prototypical lysosomal storage disorder and the first disorder to have compelling evidence of successful treatment with enzyme replacement therapy. The common clinical manifestations are hematologic cytopenias, hepatomegaly, splenomegaly, and a spectrum of skeletal pathologies. Disease expression is diverse. The rate and extent of disease progression are variable and often independent of the age at which symptoms are first reported1. Despite a long history of treatment efficacy2, there is significant heterogeneity of response among patients with regard to the maximum improvement in hematologic, visceral, bone, and other manifestations and the dynamic speed of response during therapy1-3. There have been few well-designed studies that comprehensively annotate phenotypic variation over time or measure treatment efficacy and dose response. In part, this is attributable to lack of a validated disease severity scoring system for GD1 to standardize the monitoring of progression and treatment response and to define patient cohorts in clinical studies.
DS3 is a method of expressing an integrated assessment of the burden of disease in a given patient. It can be used to monitor patient status, determine endpoints in clinical studies, classify disease phenotypes and compare patients with the same disease. Although frequently referred to as 'disease severity indices,' DS3 instruments may also include measures of disease activity and damage. DS3s utilize a minimal data set to score the patient in a comprehensive manner. They usually are structured as a group of domains (often according to organ system) that are populated with non-redundant items that are valid, reliable, use feasible, standardized methods of assessment, and that are variably weighted based on associated morbidity and mortality. A DS3 for adult GD1 patients was recently developed and subjected to successful preliminary testing for validity, reliability and feasibility4. With respect to changes over time, a minimal clinically important difference was defined. Construct validity has been partially demonstrated. Using 20 patient profiles from the International Collaborative Gaucher Group (ICGG) Gaucher Registry, the instrument was shown to correlate very well with the "gold standard" clinical global impression scale. However, larger scale testing in a population that is representative of the world wide distribution of GD1 phenotypes (including splenectomy patients) is needed and predictive validity has yet to be determined. Moreover, the DS3 has not yet been correlated with disease-specific measures of response such as achievement of therapeutic goals or broadly used biomarkers. Combining retrospective and prospective analysis, this study is designed to address these issues
- Conditions
- Gaucher Disease
- Being tested
- Imiglucerase
- Keywords
- Gaucher disease, Imiglucerase, Cerezyme, Severity score
- Medical subject headings
- Gaucher Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ImigluceraseDrug
Also called Cerezyme
Imiglucerase intravenous infusions regardless of dose or schedule of administration.
| Study group | Role | What they receive |
|---|---|---|
| Adults with Type 1 Gaucher disease (GD1) | Adults with GD1 who are cared for at one of the participating research sites whether treatment naive or treated in past or currently with imiglucerase enzyme replacement treatment. Receives: Drug: Imiglucerase |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in total DS3 severity score from baseline score
The DS3 score is calculated annually from either date of first treatment or, in untreated patients, from date of first enrollment in the ICGG Gaucher Registry
Measured: Calculated annually and assessed up to 25 years until either death, withdrawal from the study, or end of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2010 (estimated)
- Study startApr 2010
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Gaucher 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
- Cohort
- Enrolment
- 173 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Research Foundation for Lysosomal Storage Diseases, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pittsburgh
- Responsible party
- Principal investigator, Neal J Weinreb. MD, University Research Foundation for Lysosomal Storage Diseases, Inc.
- Investigators
- Neal J Weinreb, MD, Principal investigator, University Research Foundation for Lysosomal Storage Diseases, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01136304
- Sponsor's protocol ID
- URFLSD-2010-01
- Status last verified
- May 2015
- First submitted
- 31 May 2010
- Last updated
- 1 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Weinreb NJ, Cappellini MD, Cox TM, Giannini EH, Grabowski GA, Hwu WL, Mankin H, Martins AM, Sawyer C, vom Dahl S, Yeh MS, Zimran A. A validated disease severity scoring system for adults with type 1 Gaucher disease. Genet Med. 2010 Jan;12(1):44-51. doi: 10.1097/GIM.0b013e3181c39194.
PubMed 20027115Weinreb NJ, Finegold DN, Feingold E, Zeng Z, Rosenbloom BE, Shankar SP, Amato D. Evaluation of disease burden and response to treatment in adults with type 1 Gaucher disease using a validated disease severity scoring system (DS3). Orphanet J Rare Dis. 2015 May 22;10:64. doi: 10.1186/s13023-015-0280-3.
PubMed 25994334Ganz ML, Stern S, Ward A, Nalysnyk L, Selzer M, Hamed A, Weinreb N. A new framework for evaluating the health impacts of treatment for Gaucher disease type 1. Orphanet J Rare Dis. 2017 Feb 20;12(1):38. doi: 10.1186/s13023-017-0592-6.
PubMed 28219443
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Retrospective and Prospective Validation of a Disease Severity Score System (DS3) for Adults With Type 1 Gaucher Disease (GD1)
- ClinicalTrials.gov ID
- NCT01136304
- Acronym / sponsor ID
- URFLSD-2010-01
- Conditions
- Gaucher Disease
- Keywords
- Gaucher disease, Imiglucerase, Cerezyme, Severity score
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 173 participants (actual)
- Lead sponsor
- University Research Foundation for Lysosomal Storage Diseases, Inc.University, hospital or other
- Collaborators
- University of Pittsburgh
- Study start
- Apr 2010
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 3 Jun 2010 (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.
With the participation of an international consortium of investigators, the investigators will evaluate the validity of a new severity score system called DS3 for adult patients with Gaucher disease. The investigators hypothesize that initial DS3 scores will be predictive of both disease progression and patterns of response including imiglucerase dose sensitivity and completeness and maintenance of response and that sequential DS3 scores will accurately portray either clinical progression of disease or improvement in response to treatment. The investigators will also collect DNA specimens that in future research will be used in conjunction with the DS3 scores to evaluate determinants of the clinical course and the response to treatments for Gaucher disease.
Detailed description
GD1 is a prototypical lysosomal storage disorder and the first disorder to have compelling evidence of successful treatment with enzyme replacement therapy. The common clinical manifestations are hematologic cytopenias, hepatomegaly, splenomegaly, and a spectrum of skeletal pathologies. Disease expression is diverse. The rate and extent of disease progression are variable and often independent of the age at which symptoms are first reported1. Despite a long history of treatment efficacy2, there is significant heterogeneity of response among patients with regard to the maximum improvement in hematologic, visceral, bone, and other manifestations and the dynamic speed of response during therapy1-3. There have been few well-designed studies that comprehensively annotate phenotypic variation over time or measure treatment efficacy and dose response. In part, this is attributable to lack of a validated disease severity scoring system for GD1 to standardize the monitoring of progression and treatment response and to define patient cohorts in clinical studies.
DS3 is a method of expressing an integrated assessment of the burden of disease in a given patient. It can be used to monitor patient status, determine endpoints in clinical studies, classify disease phenotypes and compare patients with the same disease. Although frequently referred to as 'disease severity indices,' DS3 instruments may also include measures of disease activity and damage. DS3s utilize a minimal data set to score the patient in a comprehensive manner. They usually are structured as a group of domains (often according to organ system) that are populated with non-redundant items that are valid, reliable, use feasible, standardized methods of assessment, and that are variably weighted based on associated morbidity and mortality. A DS3 for adult GD1 patients was recently developed and subjected to successful preliminary testing for validity, reliability and feasibility4. With respect to changes over time, a minimal clinically important difference was defined. Construct validity has been partially demonstrated. Using 20 patient profiles from the International Collaborative Gaucher Group (ICGG) Gaucher Registry, the instrument was shown to correlate very well with the "gold standard" clinical global impression scale. However, larger scale testing in a population that is representative of the world wide distribution of GD1 phenotypes (including splenectomy patients) is needed and predictive validity has yet to be determined. Moreover, the DS3 has not yet been correlated with disease-specific measures of response such as achievement of therapeutic goals or broadly used biomarkers. Combining retrospective and prospective analysis, this study is designed to address these issues
Study design
- Observational model
- Cohort
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adults with Type 1 Gaucher disease (GD1) | – | Drug: ImigluceraseAdults with GD1 who are cared for at one of the participating research sites whether treatment naive or treated in past or currently with imiglucerase enzyme replacement treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Consenting adult patients with type 1 Gaucher disease who are cared for at one of the participating research sites and who are enrolled in the International Collaborative Gaucher Group Gaucher Registry
Key inclusion criteria (1 listed)
- Adult patients with Type 1 Gaucher disease regardless of treatment status who are enrolled in the International Collaborative Gaucher Group (ICCG) Gaucher Registry and who are cared for at one of the participating research sites.
Key exclusion criteria (4 listed)
- Children under the age of 18 years
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 |
|---|---|---|
| ImigluceraseAlso: CerezymeImiglucerase intravenous infusions regardless of dose or schedule of administration. | Drug | Adults with Type 1 Gaucher disease (GD1) |
Primary outcome
Change in total DS3 severity score from baseline score
Time frame: Calculated annually and assessed up to 25 years until either death, withdrawal from the study, or end of study
The DS3 score is calculated annually from either date of first treatment or, in untreated patients, from date of first enrollment in the ICGG Gaucher Registry
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 1 Jun 2015.
- Background: PubMed 20027115Weinreb NJ, Cappellini MD, Cox TM, Giannini EH, Grabowski GA, Hwu WL, Mankin H, Martins AM, Sawyer C, vom Dahl S, Yeh MS, Zimran A. A validated disease severity scoring system for adults with type 1 Gaucher disease. Genet Med. 2010 Jan;12(1):44-51. doi: 10.1097/GIM.0b013e3181c39194.
- Results publication: PubMed 25994334Weinreb NJ, Finegold DN, Feingold E, Zeng Z, Rosenbloom BE, Shankar SP, Amato D. Evaluation of disease burden and response to treatment in adults with type 1 Gaucher disease using a validated disease severity scoring system (DS3). Orphanet J Rare Dis. 2015 May 22;10:64. doi: 10.1186/s13023-015-0280-3.
- Derived from this study: PubMed 28219443Ganz ML, Stern S, Ward A, Nalysnyk L, Selzer M, Hamed A, Weinreb N. A new framework for evaluating the health impacts of treatment for Gaucher disease type 1. Orphanet J Rare Dis. 2017 Feb 20;12(1):38. doi: 10.1186/s13023-017-0592-6.
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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.
Neal J Weinreb, MD principal investigator
University Research Foundation for Lysosomal Storage Diseases, Inc.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Gaucher Disease, run by University Research Foundation for Lysosomal Storage Diseases, Inc. at 2 sites 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 1 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 1 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Change in total DS3 severity score from baseline score (time frame: Calculated annually and assessed up to 25 years until either death, withdrawal from the study, or end of study). 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 NCT01136304, which also lists 3 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 1 Jun 2015.