Clinical Importance of Glucose Regulation in Relapsing MS

Relapsing Remitting Multiple Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03004079
• Other study ID #: 19259
• Status: Recruiting
• Start date: October 2016
• Est. completion date: September 2020

Study information

• Verified date: November 2018
• Source: University of Virginia
• Contact: Myla Goldman, MD
• Phone: 434-243-6069
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: September 2020
• Est. primary completion date: September 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 59 Years

Eligibility

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

Related Conditions & MeSH terms

• Clinically Isolated Syndrome
• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Relapsing Remitting Multiple Sclerosis
• Sclerosis

Locations

Country	Name	City	State
United States	University of Virginia	Charlottesville	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
University of Virginia	National Multiple Sclerosis Society

Country where clinical trial is conducted

United States, 

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* Note: There are 47 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relapse Recovery & Hyperglycemia	Determine the relationship between mean postprandial blood glucoses (BG) and relapse recovery (complete vs. incomplete) following a standardized IVMP treatment.	Recovery from relapse at 6-months
Primary	Insulin Resistance & Relapse Severity	Determine if insulin resistance (IR), measured by the Matsuda Index, is an independent predictor of relapse severity.	At Baseline