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Autoimmunity in Neurologic Complications of Celiac Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00692861
Recruitment Status : Completed
First Posted : June 6, 2008
Last Update Posted : December 16, 2019
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)

Tracking Information
First Submitted Date June 5, 2008
First Posted Date June 6, 2008
Last Update Posted Date December 16, 2019
Study Start Date June 2, 2008
Primary Completion Date Not Provided
Current Primary Outcome Measures
 (submitted: May 23, 2013)
Antibodies to synapsin I.
Original Primary Outcome Measures Not Provided
Change History
Current Secondary Outcome Measures
 (submitted: May 23, 2013)
Antibody characterization and HLA association
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Autoimmunity in Neurologic Complications of Celiac Disease
Official Title The Role of Autoimmunity in Neurologic Complications of Celiac Disease
Brief Summary

This study, done in collaboration with Cornell University in New York, will explore the potential role of the body s immune response to gluten in ataxia. Celiac disease is an autoimmune disorder that is triggered by the ingestion of wheat gluten and related proteins in genetically susceptible individuals. Some people with celiac disease also develop ataxia, which is a loss of muscle coordination, leading to imbalance. The cause of the associated ataxia is not well understood, but it is suspected to be related to the immune response towards gluten in these patients. Preliminary results indicate that antibodies in people with celiac disease can react with brain proteins, which might have a role in the associated neurologic deficits. The aim of this study is to characterize the immune response in the ataxia that is associated with celiac disease.

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

Objective: To understand the role of the immune system in the neurologic complications of celiac disease (CD) or gluten sensitivity (GS).

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

Study Type Observational
Study Design Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Not Provided
Study Population Not Provided
Condition Ataxia
Intervention Not Provided
Study Groups/Cohorts Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: April 4, 2013)
14
Original Enrollment
 (submitted: June 5, 2008)
60
Study Completion Date January 3, 2014
Primary Completion Date Not Provided
Eligibility Criteria
  • INCLUSION CRITERIA:

We plan to evaluate serum and blood from patients with gluten sensitivity (including both biopsy-proven CD, and biopsy-negative cases with high anti-gliadin antibody titer) accompanied by cerebellar ataxia. Serum samples will be acquired prior to initiation of a gluten-free diet. Therefore, several inclusion criteria exist based on the study group:

INCLUSION CRITERIA FOR PATIENTS WITH CD PLUS CEREBELLAR ATAXIA:

  • The patient meets criteria for CD based on the modified ESPGAN 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

INCLUSION CRITERIA FOR PATIENTS WITH HEREDITARY CEREBELLAR ATAXIA WITHOUT CD:

  • 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).

INCLUSION CRITERIA FOR MATCHED-CONTROLS:

  • 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:

For all groups, if other neurological and psychiatric diagnoses are present, the individual will not qualify to participate in this study.

EXCLUSION CRITERIA FOR ALL GROUPS:

  • 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.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT00692861
Other Study ID Numbers 080153
08-N-0153
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Not Provided
Study Sponsor National Institute of Neurological Disorders and Stroke (NINDS)
Collaborators Not Provided
Investigators
Principal Investigator: Mark Hallett, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date January 3, 2014