Impaired Glucose Tolerance and Cognition in MS
Impaired Glucose Tolerance and Cognition in MS
This is a pilot study to compare cognitive performance in two groups of subjects with
 multiple sclerosis; those with normal glucose tolerance and those with impaired glucose
 tolerance. The study consists of a 2 hour oral glucose tolerance test, patient reported
 outcomes, a series of cognitive functioning tests, and outpatient physical assessment using a
 pedometer.
Investigators plan to recruit 100 compliant patients with relapsing-remitting MS who are
 willing to come fasting for an oral glucose tolerance test to determine the relationship
 between glucose tolerance and cognition in MS patients.

 Eligible study subjects expressing interest will be given a copy of the consent to review and
 will have the opportunity to ask questions. If the subject passes screening, they will be
 invited for their research visit. Signed consent form at the visit will be obtained before
 any study related procedures take place.

 Baseline Measurements: Measurements for all subjects will include age, race/ethnicity, sex,
 weight, height, waist circumference, blood pressure. Relevant medical history, current
 medications, and family history diabetes will be reviewed and documented by both subject
 report and medical records. If the subject is a woman of child-bearing ability, urine
 pregnancy test will be done in order to exclude pregnant subjects. All subjects will then
 have an IV placed and have blood drawn to measure their fasting blood glucose level. Fasting
 blood glucose above 126 ug/dl would be a screen failure for this study.

 Labs: The following labs will be drawn for all subjects.

 -  Blood glucose management (hemoglobin A1C, insulin-like growth factor, insulin) - these
 tests show how your body manages sugar

 -  Lipids & Metabolic Markers (fasting lipid profile, leptin, adiponectin) - these measure
 signal proteins in your blood for metabolism

 -  Cytokine profile - to assess impact of blood sugar and inflammatory factors (molecules
 that may indicate how well your immune system works) on recovery from your MS relapse

 -  Sodium level - to assess how your body uses water

 -  Vitamin D25 - measures amount of vitamin D in your body

 -  Neuro-filament light measurement - marker of neurodegeneration

 Oral Glucose Tolerance Test: After baseline measurements and labs are obtained, subjects will
 drink a 75g glucose drink. Labs (blood glucose and insulin levels) will be drawn every 30
 minutes for a total of 2 hours.

 In between blood draws, the subjects will undergo functional testing and complete
 questionnaires. A neurological exam will also be done that includes 8 functional systems:
 pyramidal, cerebellar, sensory, brainstem, vision, bowel and bladder, mental, and ambulation.

 Cognitive testing will include the single Digit Modalities Test (SDMT) which is a timed test
 measuring thinking speed associating numbers and symbols as well as the cogstate which is a
 computer based assessment that tests cognitive levels.In addition, all subjects will undergo
 the sloan Low Contrast Vision testing (LCVA) which assesses your ability to see letters at
 different contrast levels.

 Subjects will complete questionnaires that will ask about their fatigue level, daily
 activities, sleep habits, and how they are feeling physically, emotionally, and mentally.

 At the end of the visit subjects will be discharged to home with an ActiGraph GT3X+
 accelerometer, a waist-worn device, to measure community-based ambulation (a measure of
 physical activity). Subjects will complete 7 days of wear-time and will return accelerometers
 by mail.

 This study only requires one visit to the University of Virginia and will take approximately
 3 hours.
Inclusion Criteria:

 -  Ability to provide informed consent

 -  Diagnosis of Clinically Isolated Syndrome (CIS) or Relapsing Remitting Multiple
 Sclerosis (RRMS) confirmed by McDonald 2010 criteria

 -  EDSS < 6.5 at time of visit

 Exclusion Criteria:

 -  Diabetes type I or II

 -  use of glucose regulating medications

 -  fasting blood glucose of > 126 mg/dl

 -  known cardiac or respiratory disease

 -  morbid obesity (BMI >40)

 -  steroid exposure within 4 weeks of enrollment

 -  pregnancy or current use of hormone replacement therapy