Gaucher DiseaseNCT01358188
Exploration of Immunity in Gaucher Disease
An observational study of Gaucher Disease, run by O & O Alpan LLC at 1 site in United States.
Trial summary
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". Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Gaucher Disease
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2011to 2 May 2016
- 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: Study population will include individuals with Gaucher disease, healthy controls and individuals with primary immune dysfunction
Who may be able to join
- 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.
Who cannot join
- Severe cognitive deficits impairing decision making
- Pregnant or nursing, as these conditions may alter immunologic profile
- History of Hepatitis B, C or HIV infections
Trial locations and contacts
1 site in 1 country.
United States1 site
Lysosomal Diseases Research and Treatment Center, CFCT
Fairfax, Virginia, 22030
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Gaucher Disease
- Keywords
- Gaucher disease, immunity, inflammation, macrophage activation
- Medical subject headings
- Gaucher Disease, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Gaucher disease group | Subjects will include individuals with GD | |
| Control group | Controls will include healthy individuals and individuals with primary immune dysfunction |
What is being measured
The primary outcome is the main question the study is designed to answer.
Macrophages from patients with GD and primary immune hypo/dysfunction will show higher level of activation markers.
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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2011 (estimated)
- Study startApr 2011
- Primary completion2 May 2016
- Study completion2 May 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- O & O Alpan LLC
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ozlem Goker-Alpan, MD, O & O Alpan LLC
- Investigators
- Ozlem Goker-Alpan, M.D., Principal investigator, Center for Clinical Trials, O&O Alpan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01358188
- Sponsor's protocol ID
- 10-CFCT-01
- Status last verified
- Apr 2017
- First submitted
- 6 May 2011
- Last updated
- 4 Apr 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Goker-Alpan O. Optimal therapy in Gaucher disease. Ther Clin Risk Manag. 2010 Jul 21;6:315-23. doi: 10.2147/tcrm.s6955.
PubMed 20668714
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Study of Macrophage Activation and Cross Talk Between Immune System Elements in Subjects With Gaucher Disease
- ClinicalTrials.gov ID
- NCT01358188
- Acronym / sponsor ID
- 10-CFCT-01
- Conditions
- Gaucher Disease
- Keywords
- Gaucher disease, immunity, inflammation, macrophage activation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- O & O Alpan LLCUniversity, hospital or other
- Study start
- Apr 2011
- Primary completion
- 2 May 2016 (actual)
- Study completion
- 2 May 2016 (actual)
- First posted
- 23 May 2011 (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.
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.
Detailed description
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gaucher disease group | – | –Subjects will include individuals with GD |
| Control group | – | –Controls will include healthy individuals and individuals with primary immune dysfunction |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Study population will include individuals with Gaucher disease, healthy controls and individuals with primary immune dysfunction
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (3 listed)
- Severe cognitive deficits impairing decision making
- Pregnant or nursing, as these conditions may alter immunologic profile
- History of Hepatitis B, C or HIV infections
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
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 4 Apr 2017.
- Background: PubMed 20668714Goker-Alpan O. Optimal therapy in Gaucher disease. Ther Clin Risk Manag. 2010 Jul 21;6:315-23. doi: 10.2147/tcrm.s6955.
- O\&O Alpan LLCLink provided by the sponsor.
Related trials for Gaucher Disease
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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.
Ozlem Goker-Alpan, M.D. principal investigator
Center for Clinical Trials, O&O Alpan
1 site 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 O & O Alpan LLC at 1 site 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 6 inclusion and 3 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 4 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Macrophages from patients with GD and primary immune hypo/dysfunction will show higher level of activation markers. (time frame: 2 years). 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 NCT01358188, which also lists 1 linked publication.
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 4 Apr 2017.