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

NCT ID: NCT01136304

Last Updated: 2015-06-01

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 173 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2013-12-31

Brief 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.

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

Study Design

• Observational Model Type: COHORT

Study Groups

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.

Imiglucerase

Intervention Type: DRUG

Imiglucerase intravenous infusions regardless of dose or schedule of administration.

Interventions

Imiglucerase

Imiglucerase intravenous infusions regardless of dose or schedule of administration.

Intervention Type: DRUG

Other Intervention Names

Cerezyme

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pittsburgh

OTHER

Sponsor Role: collaborator

University Research Foundation for Lysosomal Storage Diseases, Inc.

OTHER

Sponsor Role: lead

Responsible Party

Neal J Weinreb. MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Neal J Weinreb, MD

Role: PRINCIPAL_INVESTIGATOR

University Research Foundation for Lysosomal Storage Diseases, Inc.

Locations

Tower Cancer Research Foundation

Beverly Hills, California, United States

Northwest Oncology Hematology Associates PA

Coral Springs, Florida, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 20027115 (View on PubMed)

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. 2015 May 22;10:64. doi: 10.1186/s13023-015-0280-3.

Reference Type: RESULT

PMID: 25994334 (View on PubMed)

Ganz 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.

Reference Type: DERIVED

PMID: 28219443 (View on PubMed)

Other Identifiers

URFLSD-2010-01

Identifier Type: -

Identifier Source: org_study_id