Validating a New Severity Score System for Adults With Type 1 Gaucher Disease (GD1)

Gaucher Disease Clinical Trial

Official title:

Retrospective and Prospective Validation of a Disease Severity Score System (DS3) for Adults With Type 1 Gaucher Disease (GD1)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01136304
• Other study ID #: URFLSD-2010-01
• Status: Completed
• Phase: N/A
• First received: May 31, 2010
• Last updated: May 29, 2015
• Start date: April 2010
• Est. completion date: December 2013

Study information

• Verified date: May 2015
• Source: University Research Foundation for Lysosomal Storage Diseases, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical 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. 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 173
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Study Design

Observational Model: Cohort

Related Conditions & MeSH terms

• Gaucher Disease

Intervention

Drug:
• Imiglucerase
Imiglucerase intravenous infusions regardless of dose or schedule of administration.

Locations

Country	Name	City	State
United States	Tower Cancer Research Foundation	Beverly Hills	California
United States	Northwest Oncology Hematology Associates PA	Coral Springs	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University Research Foundation for Lysosomal Storage Diseases, Inc.	University of Pittsburgh

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View Citation

Weinreb 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. 201 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Calculated annually and assessed up to 25 years until either death, withdrawal from the study, or end of study	No