Clinical trial NCT04082468: VALIDATE: Factor VIII Trending for MS Relapse
Official title: Observational Trial Evaluating Whether Elevated Factor VIII Activity During Multiple Sclerosis Relapses Serves as a Marker for Solumedrol-Resistance and Incomplete Relapse Recovery
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Multiple Sclerosis
Keywords: Relapsing remitting Multiple Sclerosis
Lead sponsor: St. Joseph's Hospital and Medical Center, Phoenix
Sponsor class: OTHER
First posted: 2019-09-09
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Acute MS relapse patients hospitalized at St. Joseph's Hospital and Medical Center in Phoenix, Arizona

Brief summary: Multiple sclerosis (MS) patients hospitalized with an acute motor or visual relapse will be consented. Factor VIII-related labs will be systematically drawn for six months. During this time, patients will be followed with clinical assessments including: Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), Low Contrast Sloan Letter Chart Testing, Symbol Digital Modality Test (SDMT), and NeuroQol. MRIs of the brain, cervical spine, and thoracic spine with and without contrast will be obtained. All patients will be treated with 1 gram IV solumedrol daily for five days per standard care. Clinical, imaging, and Factor VIII-related lab data individually or in aggregate will be correlated with relapse presence, severity, and extent of recovery following standard intravenous (IV) solumedrol treatment

Detailed description: The identification of blood tests that detect patients having Multiple Sclerosis (MS) relapses in real time could lead to a new era of MS relapse treatment. Accidental, anecdotal clinical observations suggest that transient upregulation of the intrinsic coagulation pathway, namely with elevated von Willebrand Factor antigen levels (vWF) and increased Factor VIII activity, occur with some MS relapses and that the higher the elevated plasma values, the more glucocorticoid therapy required to achieve clinical improvement.

Ten adult patients with relapsing remitting MS with or without secondary progression will be consented and enrolled in this longitudinal clinical trial. As a standard of care all patients will be treated daily with one gram IV solumedrol for five days, and all patients will have performed standard MRI's of the brain, cervical spine, and thoracic spine with and without IV contrast during hospital admission, which may occur after Solumedrol treatment.

In addition to this standard of care, patients will have a panel of labs drawn on Days: 1 (prior to any solumedrol treatment), 7, 15, 30, 45, 60, 90, 135, and 180. Neurological clinical assessments, comprising of assessing the EDSS score, the MSFC index (that looks at ambulation, hand/arm coordination, and cognitive function, comprised of the 25 foot timed walking tests, with and without any assistive devices if possible), LCSLC test, SDMT, and Neuro QoL will be conducted on Days: 1, 7, 30, 90, 180. Individual and aggregate laboratory values, neurological clinical assessment results, and MRI findings will be correlated for the presence of a MS relapse, severity of relapse, and extent of recovery from the relapse. Patients and evaluators will be blinded to the lab results.

Eligibility criteria: Inclusion Criteria:

1. Adult patients aged 18-65 with an established diagnosis of relapsing remitting multiple sclerosis (RRMS);
2. Patients with RRMS hospitalized at St. Joseph's Hospital and Medical Center in Phoenix, Arizona for an acute relapse affecting strength or vision;
3. Patients may or may not be on disease modifying treatment;
4. Entry EDSS score up to 7.0.

Exclusion Criteria:

1. Patients unable to have an MRI;
2. Patients taking any heparin products, warfarin (Coumadin), apixiban (Eliquis), dabigatran (Pradaxa), or rivaroxaban (Xarelto);
3. If stroke, tumor or other non-MS related cause is identified as the source of the patient's neurological issues.

Primary outcomes:
measure: Correlation of MS relapse recovery time with elevated lab values.
timeFrame: 180 days
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
Study officials:
affiliation: St. Joseph's Hospital/Barrow Neurological Institute
name: Amiee Borazanci, MD
role: PRINCIPAL_INVESTIGATOR
References: