Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Exploration of Immunity in Gaucher Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by O & O Alpan LLC
Sponsor:
Information provided by (Responsible Party):
Ozlem Goker-Alpan, MD, O & O Alpan LLC
ClinicalTrials.gov Identifier:
NCT01358188
First received: May 6, 2011
Last updated: October 14, 2014
Last verified: October 2014

May 6, 2011
October 14, 2014
April 2011
May 2015   (final data collection date for primary outcome measure)
Macrophages from patients with GD and primary immune hypo/dysfunction will show higher level of activation markers. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

The effect of macrophage activation on inflammation and immune response in subjects GD:

As measured by 1) The secretion of proinflammatory cytokines/chemokines ( IL-1b, TNF, IL-6 and Mip1a ) 2) The ability of macrophages to shape the differentiation profile of naïve and memory T cells.

Same as current
Complete list of historical versions of study NCT01358188 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Exploration of Immunity in Gaucher Disease
Prospective Study of Macrophage Activation and Cross Talk Between Immune System Elements in Subjects With Gaucher Disease

Gaucher disease (GD), the inherited deficiency of the lysosomal enzyme glucocerebrosidase is characterized with accumulation of abnormal lipid in cells of the immune system, called macrophages. Lipid engorged macrophages, then become activated, and are also called "Gaucher cells". The mechanisms leading to macrophage activation is not fully known, however several findings in individuals with GD, such as non-specific inflammation,clinically resembling a rheumatic disease with an increased sedimentation rate, joint pain, and extreme fatigue, in addition poor wound healing, and a predisposition to diabetes may suggest an inappropriately functioning immune system in GD. The pathways leading to macrophage activation could be related to the accumulation of lipid metabolites or through the effects of other immune cells. In this study, immunologic profiling and functional assays will be performed in peripheral blood samples from patients with GD. The identification of the immunologic basis of GD will lead to the the development of new disease markers and different treatment options.

Activated lipid engorged macrophages are the hallmark for Gaucher disease (GD). The evidence for this activation comes from the clinical finding of 1000-fold increase of serum chitotriosidase, a chitinase specifically secreted from activated macrophages. While these markers decrease with the initiation of therapy, they are not specific for organ involvement. The mechanisms of this macrophage activation is unclear, however, the presence of a non-specific inflammatory response (e.g. high sedimentation rate), poor wound healing and insulin resistance in Gaucher patients point to its clinical relevance. The finding of T, B and NK cell abnormalities in Gaucher patients also suggest either direct effects of GD lipid metabolites or indirect mechanisms via macrophages. Therefore, understanding the mechanisms of macrophage activation and the crosstalk with other immune cell types could provide mechanistic insights for pathogenesis of GD.

The investigators hypothesize that in GD the mechanisms leading macrophage activation could be related either directly to the accumulation of the lipid metabolites or through the effects of other cells of the immune system. To determine the pathways leading to macrophage dysregulation in GD, the investigators will evaluate the functional response of monocytes isolated from GD patients and profile of T cell and NK cell subsets in peripheral blood of these patients. The investigators will then assess whether macrophage dysfunction in GD is caused by an primary alteration immune response (NK and T cells response) or secondary due to the direct effects of substrate accumulation performing immunological profiling of GD patient blood samples, and through functional assays. Identification of the immunological basis of GD pathogenesis could lead to the development of both biomarkers and novel approaches for therapeutic interventions to alleviate disease symptoms. In addition, our studies will reveal novel effects of the accumulation of the lipid substrate in GD in modulating macrophage and lymphocyte subsets.

Observational
Observational Model: Case Control
Time Perspective: Prospective
Not Provided
Retention:   Samples Without DNA
Description:

Blood

Non-Probability Sample

Study population will include individuals with Gaucher disease, healthy controls and individuals with primary immune dysfunction

Gaucher Disease
Not Provided
  • Gaucher disease group
    Subjects will include individuals with GD
  • Control group
    Controls will include healthy individuals and individuals with primary immune dysfunction
Goker-Alpan O. Optimal therapy in Gaucher disease. Ther Clin Risk Manag. 2010 Jul 21;6:315-23.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
30
December 2015
May 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • History of Gaucher disease
  • Nonspecific inflammatory response evidenced by an increased ESR or positive CRP
  • Positive markers for autoimmune disorders such as ANA, RF
  • Chronic inflammatory disorders such as inflammatory bowel disease
  • NIDDM
  • Otherwise would qualify for an immunological work-up such as opportunistic or unusual infections such as atypical mycobacterial infections, unexplained lymphadenopathy.

Exclusion Criteria:

  • Severe cognitive deficits impairing decision making
  • Pregnant or nursing, as these conditions may alter immunologic profile
  • History of Hepatitis B, C or HIV infections
Both
18 Years and older
Yes
Contact: Ozlem Goker-Alpan, M.D. 571-308-1900 or 240 643 6003 ogokeralpan@oandoalpan.com
Contact: Chidima Martin, BS 571-308-1905 cmartin@oandoalpan.com
United States
 
NCT01358188
10-CFCT-01
No
Ozlem Goker-Alpan, MD, O & O Alpan LLC
O & O Alpan LLC
Not Provided
Principal Investigator: Ozlem Goker-Alpan, M.D. Center for Clinical Trials, O&O Alpan
O & O Alpan LLC
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP