What side effects are associated with this type of intervention?

Common treatments for Multiple Sclerosis, such as fingolimod, dimethyl fumarate (BG-12), and glatiramer acetate, have various side effects. Fingolimod is associated with headache, elevated liver enzymes, diarrhea, cough, flu, sinusitis, back pain, abdominal pain, bradyarrhythmia, macular edema, liver injury, diminished respiratory function, and increased risk of infections. Dimethyl fumarate can cause flushing, gastrointestinal issues, and lymphopenia. Glatiramer acetate's side effects include local injection site reactions, such as pain and redness, and systemic reactions like chest pain and palpitations. These treatments aim to manage MS symptoms but come with potential adverse effects that should be monitored.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Multiple Sclerosis (MS) that target inflammation and modulate the immune response. Interferon beta-1a (Avonex, Rebif) and interferon beta-1b (Betaseron) are among the first approved treatments, reducing the frequency of relapses. Glatiramer acetate (Copaxone) is another immunomodulatory drug that has shown efficacy in reducing relapse rates. More recent approvals include oral agents like dimethyl fumarate (Tecfidera), which has anti-inflammatory properties, and monoclonal antibodies such as natalizumab (Tysabri) and ocrelizumab (Ocrevus), which target specific immune cells involved in the inflammatory process. These treatments aim to reduce disease activity and progression by modulating the immune system and reducing inflammation.

What other types of research exist?

One promising novel alternative for Multiple Sclerosis (MS) patients considering treatment in 2024 is the use of neurotrophic factor (NTF)-secreting mesenchymal stromal cells (MSC-NTF cells). A phase II study showed that MSC-NTF cells met the primary endpoint of safety and indicated an improved rate of disease progression at early time points. This suggests potential benefits in modulating inflammation biomarkers in the cerebrospinal fluid (CSF).

← Back to Search

Other

Combination Therapies for Multiple Sclerosis

Phase 1 & 2

Recruiting

Led By Bibiana Bielekova, M.D.

Research Sponsored by National Institute of Allergy and Infectious Diseases (NIAID)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Documented sustained clinical progression of at least 0.5 CombiWISE points/year (measured by greater than or equal to 4 time-points regression analysis of CombiWISE values spanning at least 1.5 years in total)

Expanded Disability Status Scale (EDSS) 1.0-7.5

Must not have

Clinically significant medical disorders, other than MS, that require chronic treatment with immunosuppressive or immunomodulatory agents

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1.5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests four different drugs, alone or in combination, on adults with progressive multiple sclerosis who are not responding well to current treatments. The goal is to see if these drugs can reduce harmful inflammation and immune activity in the brain and spinal fluid.

Who is the study for?

Adults over 18 with progressive MS, able to walk a few steps, and currently in protocol 09-I-0032 can join. They must have shown MS progression and agree to birth control if applicable. Participants can continue their FDA-approved MS drugs but may need to stop if they change treatments.

What is being tested?

The trial tests whether Dantrolene, Pirfenidone, Pioglitazone, or clemastine fumarate alone or combined affect MS biomarkers in the brain/CSF. It aims to predict drug response based on these biomarker changes during up to an 18-month treatment period.

What are the potential side effects?

Potential side effects include allergic reactions to the medications; liver issues from Dantrolene or Pirfenidone; heart failure risk with Pioglitazone; and hypoglycemia when combining Pioglitazone with certain drugs.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

My condition has worsened by at least 0.5 points/year over 1.5 years.

Select...

My disability level is moderate to severe but I can still perform some daily activities.

Select...

I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have a health condition that needs ongoing treatment with drugs that affect the immune system.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1.5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1.5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1.5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

will be change in CombiWISE progression rate at the end of monotherapy plus combination therapy period in comparison to projected baseline disability progression.

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: MonotherapyExperimental Treatment4 Interventions

Any of the study Interventions

Group II: Combination TherapyExperimental Treatment4 Interventions

Any two-drug combination of study interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Dantrolene

2014

Completed Phase 2

~180

Pirfenidone

2006

Completed Phase 3

~2600

Pioglitazone

2005

Completed Phase 4

~27720

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Multiple Sclerosis (MS) include disease-modifying therapies (DMTs) such as beta interferons, glatiramer acetate, natalizumab, and dimethyl fumarate. Beta interferons work by reducing inflammation and modulating the immune response. Glatiramer acetate mimics myelin basic protein, distracting the immune system from attacking myelin. Natalizumab blocks the movement of immune cells across the blood-brain barrier, preventing them from reaching the central nervous system. Dimethyl fumarate activates the Nrf2 pathway, reducing oxidative stress and inflammation. These treatments are crucial for MS patients as they help to reduce the frequency and severity of relapses, slow disease progression, and minimize the development of new lesions, thereby improving quality of life.

Failed, Interrupted, or Inconclusive Trials on Immunomodulatory Treatment Strategies in Multiple Sclerosis: Update 2015-2020.