AT RISK FOR MS - Clinical Conversion of Female Monozygotic Twins Discordant for CIS/MS (ARMS)

This study has been completed.
Sponsor:
Collaborator:
National Multiple Sclerosis Society
Information provided by (Responsible Party):
Staley Brod, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:
NCT00617383
First received: February 5, 2008
Last updated: February 21, 2012
Last verified: February 2012
  Purpose

The definition of the most 'at-risk' population within highly susceptible groups would provide an opportunity for preemptive therapeutics.

A convenient, safe, and tolerable therapy that delays the onset of clinical disease during the pre-symptomatic stage of demyelinating disease would provide a therapeutic alternative to a 'wait and see' approach in subjects at 'high risk' for CIS (clinically isolated syndrome - monosymptomatic demyelinating disease) or MS.

Identical twins share the same genes and have the highest rate of shared MS. An identical female with a sister twin with MS has a 34% chance of having MS. Non concordant (no MS yet) identical (monozygotic - from the same sperm-egg zygote) female twins provide an ideal population to find out what factors predict the onset of MS in the non-affected twin.

We will recruit 30 identical female twins, one with MS and the other without MS, and obtain brain MRI and biological samples on the non-affected twin and determine if:

  • the presence of characteristic MS-like lesion(s) on baseline MRI predisposes to MS.
  • specific proteins in blood or cerebrospinal fluid predispose to the clinical expression of demyelinating disease

If we can predict by simple tests (MR brain scan and blood tests) the likelihood of the onset of MS in 'at risk' subjects, and have safe and tolerable therapies, we may be able to prevent the clinical onset of demyelinating disease (MS).


Condition
Multiple Sclerosis
Clinically Isolated Syndrome

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Determine if the Presence of Characteristic MS-like Lesion(s) on Baseline MRI Predisposes to CIS/MS in Female MZ Twins Discordant for CIS/MS.

Resource links provided by NLM:


Further study details as provided by The University of Texas Health Science Center, Houston:

Primary Outcome Measures:
  • Determine if the presence of characteristic MS-like lesion(s) on baseline MRI predisposes to CIS/MS in female MZ twins discordant for CIS/MS. [ Time Frame: 5 years or exit from study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Define the protein and microarray gene expression profile predictive of conversion to MS/CIS in female MZ twins discordant for CIS/MS. [ Time Frame: 5 years or clinical conversion to MS ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

blood for serum and peripheral mononuclear cells; optional CSF - cerebrospinal fluid at entry and exit from trail


Enrollment: 3
Study Start Date: February 2008
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Detailed Description:

Primary Objective: Determine if the presence of characteristic MS-like lesion(s) on baseline MRI predisposes to CIS/MS in female MZ twins discordant for CIS/MS.

Secondary Objective: Define the protein and microarray gene expression profile predictive of conversion to MS/CIS in female MZ twins discordant for CIS/MS.

Design and Outcomes: This is a single center, clinical study to determine if the presence of MS-like MRI brain lesions predict the rate of conversion to CIS in female MZ twins discordant for CIS/MS.

We will screen and recruit 30 subjects, and begin to follow these subjects annually for a total of 5 years to determine if MR brain scans predict CIS/MS conversion.

Interventions and Duration: Subjects will be recruited over 2 years and followed for five years with annual neurological examinations and MR brain scans.

Sample Size and Population: 30 female co-twins discordant for CIS/MS will be studied. We predict 72% of the 27% 'at risk' subjects with characteristic MR brain lesions at baseline will convert to CIS within 5 years. We predict only 6% of the 73% 'at risk' subjects without characteristic MR brain lesions at baseline will convert to CIS within 5 years.

These data will determine if paraclinical (MRI) evidence of demyelinating disease and specific blood or cerebrospinal fluid proteins predict clinical expression of disease in highly susceptible populations predicts.

  Eligibility

Ages Eligible for Study:   10 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

female monozygotic twins discordant for CIS/MS

Criteria

Inclusion Criteria:

  • 'at risk' individuals for MS - female co-twins discordant for CIS/MS.
  • 'at risk' individuals for MS who at the time of randomization have not converted to MS or CIS.
  • 'at risk' individuals will be treatment-naïve for immunomodulatory/suppressive medications.
  • < 46 years old.

Exclusion Criteria:

  • Individuals diagnosed with MS or CIS.
  • Other 'at risk' individuals who do not conform to the specific 'at risk' groups outlined above e.g., 1st degree, 2nd degree and 3rd degree relative of MS index cases.
  • Subjects over 45.
  • Use of immunomodulatory medications such as azathioprine, gold, sulfasalazine, minocycline, statins, and MTX or prednisone > 7.5 mg/day within 30 days of randomization for any reason.
  • Active drug use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements or a psychiatric disorder that is unstable or would preclude reliable participation in the study.
  • Serious illness (requiring systemic treatment and/or hospitalization) such as diabetes mellitus, renal, cardiac, or pulmonary disease. Subjects with a history of alcoholism, or in whom intellectual functioning is impaired sufficiently to interfere with the understanding of the protocol, or participation in the treatment and evaluation program.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00617383

Locations
United States, Texas
University of Texas - Houston
Houston, Texas, United States, 77030
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
National Multiple Sclerosis Society
Investigators
Principal Investigator: Staley A Brod, MD University of Texas
  More Information

Additional Information:
No publications provided

Responsible Party: Staley Brod, Professor - Neurology, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT00617383     History of Changes
Other Study ID Numbers: HSC-MS-07-0327, NMSS Pilot grant PP1464
Study First Received: February 5, 2008
Last Updated: February 21, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by The University of Texas Health Science Center, Houston:
demyelinating disease
multiple sclerosis
female monozygotic identical twins
MS
non-concordant
clinically isolated syndrome - CIS
brain MRI
proteomics

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on July 31, 2014