Clinical Importance of Glucose Regulation in Relapsing MS

Multiple Sclerosis (MS) is a neuroinflammatory and degenerative central nervous system
disorder. The majority of patients have an early relapsing-remitting course. Standard
treatment for an MS-relapse is intravenous methylprednisolone (IVMP), typically 1000 mg daily
for 3 days. Despite IVMP treatment, >40% of MS patients experience residual deficits after an
MS-relapse. Potential risk factors for poor relapse recovery remain unclear.

Elevated serum blood glucose is a common and well-defined consequence of steroid
administration, attributed to steroid-related reductions in insulin sensitivity. Individuals
with pre-treatment insulin resistance (e.g. diabetics) will exhibit an amplified
hyperglycemic response. Reduced mobility, sedentary lifestyle, and repeated exposure to
steroids- all of which are common in MS - are recognized risk factors for insulin resistance.
These factors may make MS patients particularly susceptible to steroid-induced hyperglycemia.
While, MS patients commonly receive intravenous steroids, the clinical impact of any
associated hyperglycemia is unknown.

Study Design and Methods Timeline: Study will require 3 visits over a 6 month period.

Subjects: MS subjects who are experiencing an acute relapse will be recruited for the study.
Prior to any study procedures, the PI or research coordinator will obtain full written
informed consent.

Baseline Measurements: age, race/ethnicity, sex, weight, height, waist circumference, blood
pressure, previous steroid exposure (dates, frequency, steroid type and dose), smoking
history, and family history of diabetes. Medication review will include MS disease-modifying
therapy, symptomatic medications, and non-MS-related medications. Additional MS-related
information will include dates of initial MS-symptom onset, MS diagnosis, and onset of
presenting relapse symptoms.

Oral glucose tolerance test (OGTT) & Matsuda Index: Prior to steroid administration, MS
subjects will undergo a 2-hour OGTT. OGTT and Matsuda Index will then be repeated at the 3-
and 6-month follow-up visits.

Blood studies: HgA1c (hemoglobin A1C), a fasting lipid panel (LDL-C, HDL-C, triglycerides,
and total cholesterol), insulin growth factor, vitamin D level, adiponectin level,
homocysteine level, and leptin level. All laboratory tests completed at baseline, 3- and
6-month visits.

Surveys: Subjects will complete surveys related to their perceived disability, relapse
severity and recovery, and other MS-related symptoms.

Functional testing: EDSS, MS Functional Composite, timed-walk testing, accelerometry, low
contrast visual acuity test (LCVA) and the symbol digit modality test (SDMT).

Intravenous steroid treatment: Standardized 1000 mg of intravenous methylprednisolone (IVMP)
daily for 3 days (reconstituted in 0.9% sodium chloride). IVMP will be billed to patient
insurance as part of routine clinical care.

Blood glucose monitoring: Bayer Contour Next glucometer will be used to measure capillary BG
levels 6 times daily (Subjects will be instructed to check their BG starting on the day of
screening and to continue BG checks (as above) until their return appointment 5-7 days after
steroid treatment completion for a total of 8-10 days. Subjects will be required to avoid
snacks between meals for the 3 days of IVMP treatment.

Inclusion Criteria:

- Ability to provide informed consent

- Age 18 -59 years (inclusive)

- Ability to walk continuously for 6 minutes (per patient report)

- Clinically Isolated Syndrome (CIS) or Relapsing Remitting MS (RRMS) confirmed
diagnosis by McDonald 2010 criteria

- Current MS relapse with objective findings on exam

- Relapse symptom onset within 2-weeks of screening

- Functional System Scores obtainable from a clinic visit within 6 months of the
relapse assessment visit

- EDSS < 6.5 at time of screening visit

- Inpatient, outpatient, emergency department, or inpatient observation status

Exclusion Criteria:

- Prior steroid exposure within 90 days of enrollment

- HgA1c ≥ 6.5 at baseline screening

- Evidence of concurrent infection

- Known contraindications to IV steroid treatment

- History of diabetes mellitus ( type 1 or 2) or severe hypertension

- Use of any glucose-regulating medications

- Pregnancy or current use of hormone replacement therapy