An Observational Study on the Progression of Clinically Isolated Syndrome to Multiple Sclerosis Over a 2-year Period

Multiple Sclerosis Clinical Trial

— NEO  

Official title:

A Prospective, Observational Study On The Progression Of Clinically Isolated Syndrome (CIS) To Multiple Sclerosis Over A 2-year Period

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01112657
• Other study ID #: EMR200077-504
• Status: Completed
• Phase: N/A
• First received: March 10, 2010
• Last updated: November 12, 2014
• Start date: November 2008
• Est. completion date: October 2014

Study information

• Verified date: November 2014
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Observational

Clinical Trial Summary

This is a prospective, multicentric, observational study with a 2 years recruitment period. The purpose of the study is to observe the multiple sclerosis (MS) progression of subjects since their first episode of neurological event and secondly, to determine status of anti-AQP4 immunoglobulin (IgG) antibody in MS subjects.

Description:

Multiple sclerosis is chronic, inflammatory disease of the central nervous system (CNS) characterised by areas of demyelination, or plaques, in the CNS. In 85% of subjects who later develop MS, clinical onset is with an acute or subacute episode of neurological disturbance due to a single white-matter lesion (e.g. optic neuritis, or an isolated brainstem or partial spinal-cord syndrome). This presentation is known as a Clinically Isolated Syndrome (CIS). Because a CIS is typically the earliest clinical expression of MS, research on subjects with a CIS may provide new insights into early pathological changes and pathogenetic mechanisms that might affect the course of the disorder.

In the group of subjects with optic-spinal MS (OSMS), the main lesions are typically confined to the optic nerve and spinal cord. In Asians, OSMS has similar features to the relapsing remitting form of neuromyelitis optica (NMO) seen in Westerners. It is still a matter of debate whether NMO represents a disease entity in itself or whether it is a subform of MS. Early differentiation of NMO from MS is highly desirable, as treatment options and prognoses differ widely. Recently, a new serum autoantibody (NMO-IgG) has been detected in NMO subjects. The binding sites of this autoantibody were reported to colocalize with aquaporin 4 (AQP4) water channels. Optic-spinal MS is sometime suggested to be NMO based on the frequent detection of the anti-AQP4 IgG antibody. In Taiwan, study has shown that 56% of MS subjects were of the optic-spinal type.

OBJECTIVES

The study is designed firstly, to observe the MS progression of subjects since their first episode of neurological event and secondly, to determine status of anti-AQP4 IgG antibody in MS subjects.

Primary objective:

• To describe the progression of subjects who have experienced a CIS to MS over a 2-year period

Secondary objectives:

• To assess the relationship between CIS and MS including optic-spinal MS (OSMS)

• To determine the status of anti-AQP4 IgG antibody in subjects who convert to MS

Each subject shall be followed up for 2 years after enrolment. At baseline, routine examinations shall be performed to confirm subject's neurological episode. After the baseline visit, the subject shall be instructed to return for further examination if he/she experiences a relapse. During the follow-up examinations, the treating physician shall determine whether the subject fulfil the diagnostic criteria for MS.

If subject is being diagnosed with MS, he/she shall be considered as reaching the end of his/her study participation. Further management of the MS condition will be at the discretion of the treating physician. During 2-year follow-up period, telephone calls to the subject shall be made quarterly to assess subject's neurological and/or visual status and to remind subject that he/she need to return for evaluation in the event of a relapse. All data will be collected using a standardised case report form (CRF).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 154
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 60 Years

Eligibility

Inclusion Criteria:

• Subjects aged between 6-60 years, both inclusive

• Subjects who have experienced a single, first clinical event potentially suggestive of MS within the last 2 years from study entry. The event must be a new neurological abnormality present for at least 24 hours, either mono- or polysymptomatic, other than paresthesia or vegetative dysfunction

• Subjects who have given written informed consent.

Exclusion Criteria:

• Subjects with the diagnosis of MS

• Subjects with other disease that could better explain the subject's signs and symptoms

• Subjects who are scheduled to participate in any interventional treatment trial

• Subjects who have any condition that could interfere with MRI evaluation

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Locations

Country	Name	City	State
Taiwan	Chang-Gung Memorial Hospital - Kaohsiung Branch	Kaohsiung
Taiwan	Kaohsiung Medical University, Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Chang-Gung Memorial Hospital - Linkou Branch	Taoyuan

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of subjects who convert to multiple sclerosis (MS), defined by McDonald criteria (Version 2005), over 2 years from the first episode of Clinically Isolated Syndrome (CIS)	At each and every visit, routine neurological and or ophthalmologic examinations will be performed to determine whether subject has progress to MS.	Baseline to 2 years	No
Secondary	Duration between first episode of neurological event and diagnosis of MS		Baseline to 2 years	No
Secondary	Proportion of subjects with conventional MS and optic-spinal MS (OSMS)		Baseline to 2 years	No
Secondary	Proportion of subjects with anti-AQP4 IgG antibody	Blood samples shall be taken at baseline, 12-16 weeks after baseline and end of study (for subjects who converted to MS) for anti-AQP4 IgG antibody measurements	Baseline to 2 years	No
Secondary	Association between baseline demographics/disease characteristics and progression to MS		Baseline to 2 years	No