Exploration of Immunity in Gaucher Disease
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| ClinicalTrials.gov Identifier: NCT01358188 |
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Recruitment Status :
Completed
First Posted : May 23, 2011
Last Update Posted : April 4, 2017
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| Condition or disease |
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| Gaucher Disease |
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.
| Study Type : | Observational |
| Actual Enrollment : | 33 participants |
| Observational Model: | Case-Control |
| Time Perspective: | Prospective |
| Official Title: | Prospective Study of Macrophage Activation and Cross Talk Between Immune System Elements in Subjects With Gaucher Disease |
| Study Start Date : | April 2011 |
| Actual Primary Completion Date : | May 2, 2016 |
| Actual Study Completion Date : | May 2, 2016 |
| Group/Cohort |
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Gaucher disease group
Subjects will include individuals with GD
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Control group
Controls will include healthy individuals and individuals with primary immune dysfunction
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- Macrophages from patients with GD and primary immune hypo/dysfunction will show higher level of activation markers. [ Time Frame: 2 years ]
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.
Biospecimen Retention: Samples Without DNA
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
| Sampling Method: | Non-Probability Sample |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01358188
| United States, Virginia | |
| Lysosomal Diseases Research and Treatment Center, CFCT | |
| Fairfax, Virginia, United States, 22030 | |
| Principal Investigator: | Ozlem Goker-Alpan, M.D. | Center for Clinical Trials, O&O Alpan |
Publications:
| Responsible Party: | Ozlem Goker-Alpan, MD, Chief Medical Officer, O & O Alpan LLC |
| ClinicalTrials.gov Identifier: | NCT01358188 |
| Other Study ID Numbers: |
10-CFCT-01 |
| First Posted: | May 23, 2011 Key Record Dates |
| Last Update Posted: | April 4, 2017 |
| Last Verified: | April 2017 |
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Gaucher disease immunity inflammation macrophage activation |
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Gaucher Disease Sphingolipidoses Lysosomal Storage Diseases, Nervous System Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases Nervous System Diseases |
Metabolism, Inborn Errors Genetic Diseases, Inborn Lipidoses Lipid Metabolism, Inborn Errors Lysosomal Storage Diseases Metabolic Diseases Lipid Metabolism Disorders |