Autoimmunity in Neurologic Complications of Celiac Disease
NCT ID: NCT00692861
Last Updated: 2019-12-16
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
14 participants
OBSERVATIONAL
2008-06-02
2014-01-03
Brief Summary
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People 18 years of age and older with 1) ataxia and no celiac disease, 2) ataxia plus celiac disease and 3) matched healthy control subjects will be enrolled at the NIH. People with celiac disease only will be enrolled at Cornell University.
All participants have a blood sample drawn for various tests of immune function as well as genetic tests. Healthy volunteers also have a history and physical examination if they have not had one done at NIH in the past year. Some patients may require additional clinical evaluations for clinical or diagnostic reasons.
Detailed Description
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Study population: We plan to study 15 patients with CD and ataxia, 15 patients with hereditary ataxia, and 30 healthy matched controls.
Design: Four groups of patients will be enrolled into the study. The first group will consist of patients with CD and ataxia, the second group will consist of CD patients without neurological manifestations, the third group will consist of patients with hereditary cerebellar ataxia without CD, and the final group will consist of healthy 30 race matched volunteers. The second group will not be recruited at the NIH. Standardized enzyme-linked immunosorbent assay (ELISA) techniques will used to assess the presence of synapsin I in the groups of patients. Using affinity assays, cross-reactivity of antibodies to gliadin and synapsin 1 will be evaluated. Antibody epitope mapping will be performed on those antibodies that cross-react with synapsin 1 and gliadin. HLA class II genotypic and phenotypic frequencies will be assessed and compared with the matched volunteers as an exploratory measure to look for genetic risk and protective factors in this group of patients.
Outcome measures: our outcome measures are as follows:
A. To determine whether there is an association between antibody reactivity to synapsin I and neurological deficits of CD/GS.
B. To characterize the cross-reactive antibodies in patients by determining subclass and affinity
C. To map the epitope(s) of synapsin I that are targeted in patients with cross-reactive antibodies
D. To explore HLA association in the subset of patients with CD and ataxia
Conditions
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Keywords
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Study Design
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PROSPECTIVE
Eligibility Criteria
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Inclusion Criteria
* The patient has ataxia with or without neuropathy based on clinical evaluation
* The patient is free from other neurological and psychiatric deficits
* All other known causes for ataxia have been ruled out through routine clinical evaluations
* The patient is at least 18 years old and is willing to participate in the protocol
* The patient is not taking medications that are commonly known to have immune modulating effects.
* The patient is not on a gluten free diet
* The patient tested negative for serologic markers of CD (i.e. antigliadin, antireticulin, and antiendomysial antibody testing as performed under protocol 93-N-0202)
* The patient has ataxia on routine clinical examination and no other neurological or psychiatric problems
* The patient has a known autosomal dominant ataxia (i.e., SCA, DRPLA, Friedreich s ataxia, and etc).
* They should not have CD and or ataxia based on clinical evaluation and history
* Serologic testing for antigliadin, antireticulin, and antiendomysial antibodies should reveal negative results
* They should be race and age-matched with patients with CD and the ataxia group.
* They should have no neurological or psychiatric conditions based on clinical evaluation and history
* They should not have any rheumatological or autoimmune conditions in them or in their first degree relatives.
* They should be at least 18 years of age and be able to provide consent for participation
* They should not be on any immune modulating medications.
Final diagnosis of CD will strictly follow the modified criteria of the European Society for Pediatric Gastroenterology and Nutrition (ESPGAN) and recommendations of the recently held National Institutes of Health Consensus Development Conference on Celiac Disease. Assessment and diagnosis of cerebellar ataxia will be made by magnetic resonance imaging of the brain, clinical examination and genetic testing for spinocerebellar ataxias and Friedreich s ataxia. Additional routine testing will be done if necessary to exclude other causes.
Healthy and disease control groups will be evaluated for CD and for neurological deficits. Only symptom-free, antibody-negative individuals will be recruited into these control groups. Exclusion of neurological deficits and psychiatric illness in healthy and disease control subjects will be by history and neurological examination.
Exclusion Criteria
* Subject is already on a gluten-restricted diet.
* Is taking known immune modulating therapy
* Have other neurological condition (except for neuropathy) or psychiatric condition
* Not willing to have blood drawn
* Is known to have immune dysfunction
* Being pregnant leads to numerous physiological changes. It is unclear if antibody characteristics are influenced by these changes.
18 Years
100 Years
ALL
No
Sponsors
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National Institute of Neurological Disorders and Stroke (NINDS)
NIH
Principal Investigators
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Mark Hallett, M.D.
Role: PRINCIPAL_INVESTIGATOR
National Institute of Neurological Disorders and Stroke (NINDS)
Locations
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Cornell University
New York, New York, United States
Countries
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References
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Alaedini A, Green PH. Narrative review: celiac disease: understanding a complex autoimmune disorder. Ann Intern Med. 2005 Feb 15;142(4):289-98. doi: 10.7326/0003-4819-142-4-200502150-00011.
Fasano A, Berti I, Gerarduzzi T, Not T, Colletti RB, Drago S, Elitsur Y, Green PH, Guandalini S, Hill ID, Pietzak M, Ventura A, Thorpe M, Kryszak D, Fornaroli F, Wasserman SS, Murray JA, Horvath K. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Intern Med. 2003 Feb 10;163(3):286-92. doi: 10.1001/archinte.163.3.286.
Tommasini A, Not T, Kiren V, Baldas V, Santon D, Trevisiol C, Berti I, Neri E, Gerarduzzi T, Bruno I, Lenhardt A, Zamuner E, Spano A, Crovella S, Martellossi S, Torre G, Sblattero D, Marzari R, Bradbury A, Tamburlini G, Ventura A. Mass screening for coeliac disease using antihuman transglutaminase antibody assay. Arch Dis Child. 2004 Jun;89(6):512-5. doi: 10.1136/adc.2003.029603.
Other Identifiers
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08-N-0153
Identifier Type: -
Identifier Source: secondary_id
080153
Identifier Type: -
Identifier Source: org_study_id