## Protocol Section
### Identification Module
**NCT ID:** NCT03004079

**Brief Title:** Clinical Importance of Glucose Regulation in Relapsing MS

**Official Title:** Assessment of the Clinical Importance of Insulin Resistance & Steroid-Associated Hyperglycemia in Relapsing Multiple Sclerosis

#### Organization Study ID Info
**ID:** 19259
#### Organization
**Class:** OTHER
**Full Name:** University of Virginia
### Status Module
#### Completion Date
**Date:** 2020-09

**Type:** ESTIMATED

#### Expanded Access Info
**Last Known Status:** RECRUITING
#### Last Update Post Date
**Date:** 2018-11-07

**Type:** ACTUAL

**Last Update Submit Date:** 2018-11-05

**Overall Status:** UNKNOWN

#### Primary Completion Date
**Date:** 2020-09

**Type:** ESTIMATED

#### Start Date
**Date:** 2016-10

**Status Verified Date:** 2018-11

#### Study First Post Date
**Date:** 2016-12-28
**Type:** ESTIMATED
**Study First Submit Date:** 2016-11-02
**Study First Submit QC Date:** 2016-12-21
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** National Multiple Sclerosis Society

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Virginia

#### Responsible Party

**Investigator Affiliation:** University of Virginia

**Investigator Full Name:** Myla Goldman, MD

**Investigator Title:** Associate Professor of the Department of Neurology

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The purpose of this study is to assess the relationship of blood glucose levels in persons with Multiple Sclerosis (MS) who have experienced a relapse and will be receiving intravenous steroids for the relapse, to their recovery from the relapse.

Steroid exposure commonly leads to elevated serum blood glucose, however, standardized monitoring of blood glucose levels in the outpatient setting is not common. The clinical impact of any associated elevated blood glucose during steroid administration is unknown. We hypothesize that the blood glucose response to steroid treatment is clinically relevant to the MS-relapse recovery.

**Detailed Description:** 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.

### Conditions Module

**Conditions:**

- Relapsing Remitting Multiple Sclerosis

- Clinically Isolated Syndrome

### Design Module

#### Design Info

**Observational Model:** CASE_ONLY

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 160

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Outcomes Module

#### Primary Outcomes

**Description:** Determine the relationship between mean postprandial blood glucoses (BG) and relapse recovery (complete vs. incomplete) following a standardized IVMP treatment.

**Measure:** Relapse Recovery & Hyperglycemia

**Time Frame:** Recovery from relapse at 6-months

**Description:** Determine if insulin resistance (IR), measured by the Matsuda Index, is an independent predictor of relapse severity.

**Measure:** Insulin Resistance & Relapse Severity

**Time Frame:** At Baseline

### Eligibility Module

**Eligibility Criteria:** 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

**Maximum Age:** 59 Years

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

**Study Population:** Adults aged 18-54 (inclusive) with a diagnosis of clinically isolated syndrome or relapsing remitting multiple sclerosis with an acute attack (relapse).

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Name:** Myla Goldman, MD

**Phone:** 434-243-6069

**Role:** CONTACT

**Contact 2:**

**Email:** rcoleman@virginia.edu

**Name:** Rachael Coleman, MPH

**Phone:** 434-297-4102

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Charlottesville

**Contacts:**

***Contact 1:***

- **Email:** rcoleman@virginia.edu

- **Name:** Rachael Coleman, MPH

- **Phone:** 434-297-4102

- **Role:** CONTACT

***Contact 2:***

- **Name:** Myla Goldman, MD

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** United States

**Facility:** University of Virginia

**State:** Virginia

**Status:** RECRUITING

**Zip:** 22903

#### Overall Officials

**Official 1:**

**Affiliation:** University of Virginia

**Name:** Myla Goldman, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

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## Derived Section

### Condition Browse Module - Ancestors

- ID: D000010335

- Term: Pathologic Processes

- ID: D000020278

- Term: Demyelinating Autoimmune Diseases, CNS

- ID: D000020274

- Term: Autoimmune Diseases of the Nervous System

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000003711

- Term: Demyelinating Diseases

- ID: D000001327

- Term: Autoimmune Diseases

- ID: D000007154

- Term: Immune System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

### Condition Browse Module - Browse Leaves

- ID: M12060

- Name: Multiple Sclerosis

- Relevance: HIGH

- As Found: Multiple Sclerosis

- ID: M15415

- Name: Sclerosis

- Relevance: HIGH

- As Found: Sclerosis

- ID: M10370

- Name: Insulin Resistance

- Relevance: LOW

- As Found: Unknown

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M22314

- Name: Multiple Sclerosis, Relapsing-Remitting

- Relevance: HIGH

- As Found: Relapsing Remitting Multiple Sclerosis

- ID: M9994

- Name: Hyperglycemia

- Relevance: LOW

- As Found: Unknown

- ID: M4629

- Name: Autoimmune Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M22098

- Name: Demyelinating Autoimmune Diseases, CNS

- Relevance: LOW

- As Found: Unknown

- ID: M22094

- Name: Autoimmune Diseases of the Nervous System

- Relevance: LOW

- As Found: Unknown

- ID: M6909

- Name: Demyelinating Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000009103

- Term: Multiple Sclerosis

- ID: D000020529

- Term: Multiple Sclerosis, Relapsing-Remitting

- ID: D000012598

- Term: Sclerosis

### Intervention Browse Module - Browse Branches

- Abbrev: Hypo

- Name: Hypoglycemic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M10365

- Name: Insulin

- Relevance: LOW

- As Found: Unknown

- ID: M173166

- Name: Insulin, Globin Zinc

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
