AT RISK FOR MS - Clinical Conversion of Female Monozygotic Twins Discordant for CIS/MS - Full Text View

Sponsors and Collaborators:	The University of Texas Health Science Center, Houston National Multiple Sclerosis Society
Information provided by:	The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:	NCT00617383

Purpose

The definition of the most 'at-risk' population within highly susceptible groups would provide an opportunity for pre-emptive 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

MedlinePlus related topics: Multiple Sclerosis

U.S. FDA Resources

Study Type:	Observational
Study Design:	Cohort, 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.

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

Biospecimen Description:

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

Estimated Enrollment:	30
Study Start Date:	February 2008
Estimated Study Completion Date:	February 2015
Estimated Primary Completion Date:	February 2015 (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 singlecenter, 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, sulfazalasine, 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00617383

Contacts

Contact: Staley A Brod, MD	713.500.7046	sbrod@mac.com
Contact: Lucille Lambert	713.500.7135	lucille.lambert@uth.tmc.edu

Locations

United States, Texas
University of Texas - Houston	Recruiting
Houston, Texas, United States, 77030
Contact: Staley A Brod, MD 713-500-7046 sbrod@mac.com
Contact: Lucille Lambert 713.500.7135 Lucille.Lambert@uth.tmc.edu
Principal Investigator: Staley A Brod, MD

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:

Staley Armstrong Brod, M.D. Professor of Neurology, Multiple Sclerosis Research Group This link exits the ClinicalTrials.gov site

National Multiple Sclerosis Society This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	The University of Texas Health Science Center, Houston ( Staley A. Brod, M.D. )
Study ID Numbers:	HSC-MS-07-0327, NMSS Pilot grant PP1464
Study First Received:	February 5, 2008
Last Updated:	February 17, 2009
ClinicalTrials.gov Identifier:	NCT00617383 History of Changes
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

Study placed in the following topic categories:

Autoimmune Diseases
Multiple Sclerosis
Demyelinating Diseases

Demyelinating Autoimmune Diseases, CNS
Sclerosis
Autoimmune Diseases of the Nervous System

Additional relevant MeSH terms:

Disease
Pathologic Processes
Autoimmune Diseases
Multiple Sclerosis
Immune System Diseases
Demyelinating Diseases

Syndrome
Nervous System Diseases
Demyelinating Autoimmune Diseases, CNS
Sclerosis
Autoimmune Diseases of the Nervous System

ClinicalTrials.gov processed this record on May 07, 2009