Corticosteroids for Multiple Sclerosis

Overseen By Shari L Sawney

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)

Must not be taking: Systemic steroids

Disqualifiers: Pregnancy, Diabetes, Claustrophobia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 3 days

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a short-term, high-dose course of corticosteroids can heal specific types of lesions in people with multiple sclerosis (MS). These lesions, known as ring-enhancing lesions, are considered harder to heal. Participants will either receive no treatment or corticosteroids (such as Methylprednisolone or Prednisone) for three days, administered intravenously or orally. The trial seeks individuals with MS who have had a specific type of lesion on a brain MRI and are already part of another study at the NINDS clinic. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but you cannot have taken systemic steroids in the past 30 days.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both methylprednisolone and prednisone are generally well-tolerated for treating flare-ups in multiple sclerosis (MS). Studies indicate that intravenous methylprednisolone, commonly used for MS, is effective and safe for easing symptoms during a flare-up. It may help reduce the frequency of flare-ups and improve MRI results over time, although it might not work for everyone.

Research has found prednisone effective when used after methylprednisolone for MS flare-ups. However, about 20% to 35% of MS patients may not respond to high-dose corticosteroids during a flare-up.

Both treatments have been used to manage MS flare-ups, suggesting they are generally safe. However, like any treatment, possible risks and side effects exist. Participants should discuss these with their doctor before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for multiple sclerosis because they offer rapid relief through different administration methods. Methylprednisolone is given intravenously, which can be ideal for patients needing quick, high-dose effects right into the bloodstream. On the other hand, prednisone is taken orally, providing a convenient option for those who prefer not to undergo IV therapy. Both treatments aim to reduce inflammation swiftly, potentially offering faster symptom relief than many standard therapies, which often take longer to show results.

What evidence suggests that this trial's treatments could be effective for multiple sclerosis?

Research has shown that corticosteroids, like methylprednisolone, help manage flare-ups in multiple sclerosis (MS). In this trial, participants will receive either a 3-day course of intravenous methylprednisolone or a 3-day course of oral prednisone. Studies have found that intravenous methylprednisolone is often used during MS relapses to reduce symptoms and may improve long-term outcomes, such as MRI results and slowing disability progression. Methylprednisolone can decrease the number of MS relapses and may help with lesions seen on MRIs. Prednisone, another corticosteroid under study in this trial, is also used to manage MS symptoms, though less specific data exists about its use for certain types of lesions. Overall, corticosteroids play a crucial role in managing MS symptoms, with evidence supporting their effectiveness in easing issues related to relapses. ^{4 5 6 7 8}

Who Is on the Research Team?

Daniel S Reich, M.D.

Principal Investigator

National Institute of Neurological Disorders and Stroke (NINDS)

Are You a Good Fit for This Trial?

Adults 25+ with Multiple Sclerosis (MS) who have a specific type of lesion on their brain MRI, are already part of another NINDS study, and can undergo MRI scans without issues. They shouldn't have used systemic steroids in the last month or be experiencing new MS symptoms. Pregnant or breastfeeding individuals and those with certain medical conditions like diabetes or gastric ulcers cannot participate.

Inclusion Criteria

I have been diagnosed with multiple sclerosis.

Ability to provide informed consent

Simultaneously participates in another screening or natural history protocol within the NINDS Neuroimmunology Clinic at the time of study entry

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 MRI-compatible or cannot be removed)

I have new symptoms from an MS flare-up in the last 2 weeks.

Pregnancy or current breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Baseline

Participants undergo baseline assessments including medical history, physical exam, blood and urine tests, neurological exams, and MRIs

1 visit

Treatment

Participants receive a 3-day course of high-dose corticosteroids, either intravenous methylprednisolone or oral prednisone

3 days

Follow-up

Participants are monitored for safety and effectiveness with follow-up visits at week 13 and week 25, including clinical evaluations, blood tests, and MRIs

25 weeks

2 visits (in-person) at weeks 13 and 25

What Are the Treatments Tested in This Trial?

Interventions

• Methylprednisolone
• Prednisone

Trial Overview The trial is testing if a short-term high-dose corticosteroid treatment helps heal ring-enhancing lesions in MS patients better than no treatment. Participants will either receive three days of high-dose methylprednisolone intravenously or orally, along with stomach protection medication, followed by two follow-up visits for assessment.

How Is the Trial Designed?

Group I: prednisone Experimental Treatment 1 Intervention

3-day course of oral prednisone 1250 mg/day

Group II: Methylprednisolone Experimental Treatment 1 Intervention

3 day course of intravenous methylprednisolone 1000 mg/day

Methylprednisolone is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Medrol for:

• Allergic reactions
• Blood disorders
• Cancer
• Eye diseases
• Immune system disorders
• Inflammatory diseases
• Respiratory diseases
• Skin diseases

Approved in European Union as Depo-Medrol for:

• Allergic reactions
• Blood disorders
• Cancer
• Eye diseases
• Immune system disorders
• Inflammatory diseases
• Respiratory diseases
• Skin diseases

Approved in Canada as Solu-Medrol for:

• Allergic reactions
• Blood disorders
• Cancer
• Eye diseases
• Immune system disorders
• Inflammatory diseases
• Respiratory diseases
• Skin diseases

Who Is Running the Clinical Trial?

National Institute of Neurological Disorders and Stroke (NINDS)

Lead Sponsor

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

A survey of sports medicine physicians revealed that 47% prescribe methylprednisolone taper (Medrol Dosepak) for sports injuries, particularly in patients aged 40 and younger, with postinjury disease being the most common reason for its use.

Concerns about complications, especially the risk of osteonecrosis (reported in 8.5% of prescribers), and a lack of proven efficacy were significant reasons for the 52% of physicians who chose not to prescribe Medrol Dosepak.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survey of orthopaedic and sports medicine physicians regarding use of medrol dosepak for sports injuries. Langer, P., Fadale, P., Hulstyn, M., et al.[2018]

In a study of 15 patients previously diagnosed with corticosteroid-induced arachnoiditis, only 3 exhibited the clinical symptoms of arachnoiditis, suggesting a low incidence of the condition among those affected.

The findings indicate that the severity of radiological changes did not correlate with the severity of symptoms, leading to the conclusion that methylprednisolone acetate (Depo-Medrol) should be avoided in procedures involving the thecal sac due to potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Depo-Medrol and myelographic arachnoiditis. Johnson, A., Ryan, MD., Roche, J.[2021]

Two patients experienced vision loss in one eye after receiving a methylprednisolone acetate injection for chronic nasal inflammation, indicating a potential risk associated with this treatment.

The visual loss was linked to embolic occlusion of retinal and choroidal blood vessels, likely caused by microcrystal aggregates from the injected medication, highlighting a serious safety concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinal and choroidal microvascular embolism after intranasal corticosteroid injection. Whiteman, DW., Rosen, DA., Pinkerton, RM.[2022]

Methylprednisolone acetate (Depo-Medrol) injections via epidural or intrathecal routes can effectively relieve diskogenic back pain and radiculopathy when conservative treatments have failed, particularly if symptoms have lasted less than three months.

Corticosteroid injections are less effective for patients with chronic symptoms lasting over three months or those who have previously undergone surgery, suggesting a limited window for optimal use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of diskogenic pain using epidural and intrathecal steroids. Brown, FW.[2019]

Inadvertent injection of methylprednisolone acetate into the eye during vitrectomy can lead to severe retinal toxicity, resulting in significant vision loss and complications such as retinal necrosis and optic nerve damage.

This case highlights the critical need for careful identification of medications during eye surgeries to prevent serious adverse effects associated with incorrect injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinal necrosis secondary to inadvertent intravitreal methylprednisolone acetate (depo-medrol) injection during pars plana vitrectomy. Yonekawa, Y., Sun, G., D'Amico, DJ., et al.[2014]

In a study involving three patients with optic neuritis, treatment with sub-Tenon's depo-methylprednisolone acetate followed by oral prednisolone led to rapid improvement in visual acuity, achieving normal vision (6/6) within 2-3 weeks.

The treatment was found to be safe, with no recurrence of optic neuritis or neurological deficits observed during follow-ups of 3 to 5 years, indicating its long-term efficacy for African patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of optic neuritis in a developing African country. Omoti, AE., Waziri-Erameh, MJ.[2018]

In a study of 901 patients with relapsing-remitting multiple sclerosis, methylprednisolone (MP) pulse therapy was administered with a mean frequency of 4 times, showing that the majority of patients received treatment multiple times, indicating its common use in managing acute exacerbations.

The study found that female patients were approximately 3.7 times more likely to seek MP pulse therapy compared to male patients, suggesting a gender difference in treatment-seeking behavior for MS management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary study related the incidence of methylprednisolone pulse therapy in patients visited multiple sclerosis clinic located at the isfahan kashani hospital. Tolou-Ghamari, Z., Shaygannejad, V., Ashtari, F.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6788278/

High-dose oral methylprednisolone for the treatment of ... Results. 92 patients were included (88% had recurrent remitting multiple sclerosis). Median Expanded Disability Status Scale score was 2 (IRC: ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6858912/

Treatment Effectiveness for Resolution of Multiple Sclerosis ... In a study by Nickerson and Marrie, 30% of patients given IVMP and 38% of those given OCS reported that their treatment worsened their relapse ...

3. jneuroinflammation.biomedcentral.com jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-022-02583-y

Immunoadsorption versus double-dose methylprednisolone in ... Intravenous methylprednisolone is the standard treatment for a multiple sclerosis relapse; however, this fails to improve symptoms in up to ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0039128X19300856

Long term effects of corticosteroids in multiple sclerosis ... There is some evidence that pulsed treatment with methylprednisolone have beneficial long-term effects on relapse rate, MRI findings and disability progression.

5. practicalneurology.com practicalneurology.com/diseases-diagnoses/ms-immune-disorders/relapse-management-in-multiple-sclerosis-corticosteroids-remain-the-linchpin-of-therapies/32084/

Multiple Sclerosis Relapse: Corticosteroids Key A randomized clinical trial5 compared the efficacy and safety of high-dose oral methylprednisolone vs IVMP for treatment of MS relapses at 4 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7440146/

Would it be recommended treating multiple sclerosis relapses ... Regarding relapses management, the use of intravenous corticosteroids and hospitalization during MS relapses increase the risk of viral exposure ...

7. tandfonline.com tandfonline.com/doi/full/10.2147/DNND.S208815

Efficacy, safety, and quality-of-life of treatments for acute ... RCTs indicate IVMP and RCI are efficacious and well tolerated treatments for MS relapse. Overall, many RCTs were dated, with sample sizes of ...

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK544340/

Methylprednisolone - StatPearls - NCBI Bookshelf - NIH The goal is to minimize adverse effects while maximizing therapeutic efficacy, thus improving patient outcomes and elevating standards of care.