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Effect of Corticosteroids on Inflammation at the Edge of Acute Multiple Sclerosis Plaques

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ClinicalTrials.gov Identifier: NCT02784210
Recruitment Status : Recruiting
First Posted : May 27, 2016
Last Update Posted : November 24, 2021
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Brief Summary:

Background:

Multiple sclerosis (MS) affects the brain, spinal cord, and optic nerves. MS lesions can appear on the MRI (magnetic resonance imaging) scans in many ways. Sometimes they light up from the outer edge and fill inward. This is called ring enhancement. Researchers think this type of lesion may not heal as well as others. Corticosteroids are the standard treatment to reduce symptoms of MS relapse. But there is no standard treatment for people with enhancing MS lesions without signs of MS relapse. Researchers want to see if a short-term high-dose course of corticosteroids helps heal those lesions.

Objective:

To study the effects of short-term high-dose corticosteroids on ring-enhancing MS.

Eligibility:

Adults ages 25 and older who:

  • Have MS and a rim-enhancing lesion on a prior brain MRI
  • Are enrolled in another NINDS protocol

Design:

Participants will be screened under another protocol

Participants will be randomly assigned to get either no treatment or 3 days of treatment with a corticosteroid.

Participants will have:

  • 1 baseline visit
  • 3 days of high-dose steroids, intravenous or oral. If IV, participants will receive methylprednisolone by IV each day. Participants will also be prescribed medicine to protect their stomach.
  • Follow-up visits will be at week 13 and week 25 after randomization to treatment or no treatment.

Visits include medical history and physical exam. Participants will have blood and urine tests. Participants will also have neurological exams and MRIs. Participants lie on a table that slides into a cylinder. They are in the scanner 1.5-2 hours. They get a dye through a catheter: A needle guides a thin plastic tube into an arm vein.


Condition or disease Intervention/treatment Phase
Multiple Sclerosis Drug: Methylprednisolone Drug: Prednisone Phase 2

Detailed Description:

Objectives. The primary aim of this pilot study is to assess the effects of short-term, high-dose corticosteroid administration on the 12-week evolution of multiple sclerosis lesions with centripetal enhancement pattern on magnetic resonance imaging (MRI), in particular with respect to the development of a hypointense rim on 7-tesla phase images. In our prior work, the phase rim has been associated with persistent deleterious inflammation with poor repair and ongoing neurodegeneration within lesions.

Study population. Up to 30 multiple sclerosis patients with asymptomatic contrast-enhancing lesions will be enrolled. Patients are randomly assigned to either 3 days of corticosteroids (intravenous methylprednisolone a 1000 mg/day or oral prednisone at 1250mg/day) or to no treatment.

Design. This is a multi-site study with Johns Hopkins University. Some analysis of identifiable data will be conducted at Johns Hopkins University JHU under a reliance agreement. Patients will not be consented to the study or participate in study interventions/procedures at JHU. Patients undergo serial brain MRIs with gadolinium-based contrast agent on both 3- and 7-tesla scanners over an approximate 25-week period. 3-tesla scans are obtained at baseline and week 25. 7-tesla scans are obtained at baseline and at weeks 13 and 25. Participants with one or more centripetal/rim-enhancing lesions at the baseline scan are randomized and followed. Clinical evaluation and blood testing are performed at baseline and weeks 13 and 25.

Outcome measures. The primary outcome measure is the presence or absence, on the week-13 7-tesla scan, of a hypointense phase rim in each of the lesions followed over time. Secondary outcome measures include the presence or absence of a hypointense phase rim at week 25, as well as the lesion volume and intralesional median R1 relaxation rate at weeks 13 and 25. From 3-tesla scans, we will measure the change in normalized intralesional proton density-weighted and T1-weighted signal, as well as the R1 relaxation rate, between baseline and week 25. We will also assess for the presence or absence of a hypointense phase at 3T. Additional exploratory outcome measures, including clinical and immunological assessments, will also be collected.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: The Effect of Corticosteroids on Inflammation at the Edge of Acute Multiple Sclerosis Plaques: An Investigator-Blinded Study
Actual Study Start Date : October 5, 2016
Estimated Primary Completion Date : April 30, 2023
Estimated Study Completion Date : April 30, 2023


Arm Intervention/treatment
Experimental: Methylprednisolone
3 day course of intravenous methylprednisolone 1000 mg/day
Drug: Methylprednisolone
3 days of corticosteroids (intravenous methylprednisolone at 1000 mg/day

Experimental: prednisone
3-day course of oral prednisone 1250 mg/day
Drug: Prednisone
3 days of corticosteroids (oral prednisone at 1250 mg/day




Primary Outcome Measures :
  1. the presence or absence of a hypointense phase rim around each lesion followed over time [ Time Frame: at 13 weeks ]
    At week 13, the presence or absence of a hypointense phase rim around each lesion followed over time.


Secondary Outcome Measures :
  1. Lesion volume and intralesional median R1 relaxation rate as determined from the 7T MP2RAGE scan, [ Time Frame: at week 13 and 25 ]
    Lesion volume and intralesional median R1 relaxation rate at weeks 13 and 25, as determined from the 7T MP2RAGE scan, comparing corticosteroid and no-treatment groups.

  2. The presence or absence of a hypointense phase rim around each lesion followed over time. [ Time Frame: at week 25 ]
    At week 25, the presence or absence of a hypointense phase rim around each lesion followed over time.

  3. The presence or absence of a 3T hypointense phase rim around each lesion [ Time Frame: at week 25 ]
    The presence or absence of a 3T hypointense phase rim around each lesion at week and 25



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Multiple sclerosis, as defined by the 2017 Revised McDonald Criteria;
  • Age 25 or older;
  • Ability to provide informed consent;
  • Able to participate in study procedures and provide high-quality clinical research and imaging data, based on limited artifacts on prior MRI scans and, when possible to determine;
  • Presence of a gadolinium enhancing lesion on the screening (3T or 7T) brain MRI that demonstrates either centripetal/rim enhancement or a phase rim, or both;
  • Simultaneously participates in another screening or natural history protocol within the NINDS Neuroimmunology Clinic at the time of study entry.
  • Willing to use birth control if able to conceive a child

EXCLUSION CRITERIA:

  • Medical contraindications for MRI (e.g., any non organic implant or other device such as a cardiac pacemaker or infusion pump or other metallic implants, objects, or body piercings that are not MRIcompatible or cannot be removed);
  • Psychological contraindications for MRI (e.g., claustrophobia), to be assessed at the time the medical history is collected;
  • Treatment with systemic steroids in previous 30 days (non-systemic administration of steroids, such as topical or local injection, is acceptable);
  • Experiencing new neurological symptoms, with onset in previous 2 weeks, attributable to MS relapse;
  • Pregnancy or current breastfeeding;
  • Screening labs demonstrating estimated glomerular filtration rate <60 mL/min;
  • Known hypersensitivity to gadolinium-based contrast agents;
  • Medical contraindications to corticosteroid administration (e.g., diabetes, gastric ulcer)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02784210


Contacts
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Contact: Joan M Ohayon, C.R.N.P. (301) 496-3825 eatonj@ninds.nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Daniel S Reich, M.D. National Institutes of Health Clinical Center (CC)
Additional Information:
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Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier: NCT02784210    
Other Study ID Numbers: 160114
16-N-0114
First Posted: May 27, 2016    Key Record Dates
Last Update Posted: November 24, 2021
Last Verified: November 22, 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):
Centripetal Enhancement
MRI
7 Tesla
Gadolinium
MS
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Inflammation
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Prednisone
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents