Effect of Corticosteroids on Inflammation at the Edge of Acute Multiple Sclerosis Plaques
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02784210|
Recruitment Status : Recruiting
First Posted : May 27, 2016
Last Update Posted : November 24, 2021
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.
To study the effects of short-term high-dose corticosteroids on ring-enhancing MS.
Adults ages 25 and older who:
- Have MS and a rim-enhancing lesion on a prior brain MRI
- Are enrolled in another NINDS protocol
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|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|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|
3 day course of intravenous methylprednisolone 1000 mg/day
3 days of corticosteroids (intravenous methylprednisolone at 1000 mg/day
3-day course of oral prednisone 1250 mg/day
3 days of corticosteroids (oral prednisone at 1250 mg/day
- 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.
- 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.
- 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.
- 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
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
|Contact: Joan M Ohayon, C.R.N.P.||(301) firstname.lastname@example.org|
|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 email@example.com|
|Principal Investigator:||Daniel S Reich, M.D.||National Institutes of Health Clinical Center (CC)|