Treatment of Multiple Sclerosis With Copaxone and Albuterol

Study Overview
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Brief Summary
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The purpose of this study is to determine the effects of glatiramer acetate (Copaxone) alone compared to Copaxone plus albuterol in patients with Multiple Sclerosis (MS). MS is thought to be an autoimmune disease of the central nervous system. Certain white blood cells of the immune system become abnormally active and mistakenly attack the myelin of nerve fibers. Myelin is a fatty sheath that surrounds nerve fibers and insulates the nerve like insulation around an electrical wire. Without proper myelin insulation, messages sent between the brain and other parts of the body may be confused or fail completely. Damage to myelin causes the symptoms of MS. The most common form of MS is known as relapsing-remitting (RR), where partial or total recovery occurs after attacks. Four therapies are currently approved for the treatment of MS. These therapies, however, are only moderately effective and can cause undesirable side effects. For this reason, there is a need to find new therapies that have minimal side effects and may stop the disease from getting worse.

Detailed Description
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MS is a chronic inflammatory disease of the central nervous system characterized by focal T cell and macrophage infiltrates that lead to demyelination and loss of neurologic function. Four therapies are currently approved for the treatment of MS. Three of these are approved for the treatment of patients with the relapsing-remitting (RR) form of MS, in which patients have clinical exacerbations followed by partial or complete recovery of function. These treatments are only modestly effective and are associated with significant toxicity, often causing patients to delay therapy for significant lengths of time. Thus, there is a need to find therapies with low toxicities that can be administered early during the disease course with the potential for arresting the disease. During the pre-treatment phase, patients undergo neurological exams, including the extended disability status scale (EDSS), Ambulation Index (AI), disease steps (DS) scale MS functional composite score, PASAT, 9 hole peg test, and the 25 foot walking time. A 12-lead electrocardiogram (EKG) and chest x-ray are performed. Serum chemistry is assessed as well as electrolyte and thyroid stimulating hormone (TSH) levels. A brain MRI (with and without gadolinium), urinalysis, and urine pregnancy test (for women of reproductive potential) are performed. Blood is collected for mechanistic studies. In the treatment phase, patients are assigned randomly to 1 of 2 study arms: Arm 1: Copaxone plus placebo. Arm 2: Copaxone plus albuterol. At the treatment visits, blood is collected and neurological exams and a brain MRI are performed. A pregnancy test is administered to women of reproductive potential. Neurological exams are performed every 6 months. MRIs are performed at baseline, Year 1, and Year 2. At the end of the study, patients have a complete physical exam, a neurological exam, and a brain MRI.

Official Title
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Treatment of Multiple Sclerosis With Copaxone (Glatiramer Acetate) and Albuterol

Conditions
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Autoimmune Diseases, Multiple Sclerosis

Intervention / Treatment
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* Drug: Glatiramer acetate
* Drug: Albuterol
* Drug: Albuterol placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients may be eligible for this study if they: Have been diagnosed with RR-MS, within 2 years of diagnosis. Are 18-55 years old. Have RR-MS with evidence of demyelination on MRI scanning of the brain. Have extended disability status scale (EDSS) scores between 0 and 3.5. Have not taken Copaxone or oral myelin. Have not had immunomodulating therapy for the past 3 months. Have not taken immunosuppressants. Have not had steroid treatment 1 month before entry. Have no evidence of active infection or cancer. Exclusion Criteria Patients may not be eligible for this study if they: Have a normal brain MRI. Are not willing to practice contraception (applies to women who are able to have children). Are pregnant or breast-feeding. Are currently taking any of the following drugs: beta2-adrenergic agonist or antagonist, diuretics, tricyclic antidepressants, or monoamine oxidase inhibitors. Have heart, blood, liver, or kidney problems. Have a disease that affects blood clotting or lung function. Have abnormalities that relate to the endocrine system. Have a history of alcohol or drug abuse within 6 months of enrollment. Have been diagnosed with primary progressive MS, in which the disease slowly worsens without periods of recovery.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Participants will receive Copaxone and albuterol placebo | Drug: Glatiramer acetate<br>* 20 mg administered subcutaneously daily<br>Drug: Albuterol placebo<br>* Oral placebo capsules will be taken daily<br>|
| Experimental: 2<br>Participants will receive Copaxone and albuterol | Drug: Glatiramer acetate<br>* 20 mg administered subcutaneously daily<br>Drug: Albuterol<br>* 2 mg or 4 mg oral capsules taken daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in each participant's disease status, as measured by the Multiple Sclerosis Functional Composite score (MSFC) |  | Throughout study | 
| Glatiramer acetate-specific cytokine secretion of IL-13 cytokine secretion and IFN-gamma secretion by glatiramer acetate-reactive T-cell lines |  | At Months 3, 6, and 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in IL-5 secretion in the supernatants of lines stimulated with glatiramer acetate |  | Throughout study | 
| Change in percentage of IL-12-producing monocytes by intracytoplasmic staining |  | Throughout study | 
| Time to first exacerbation |  | Throughout study | 
| Number and severity of exacerbations |  | Throughout study | 
| MRI evidence as measured by T2 lesion volume, number of enhancing lesions on T1 weighted images, and measurements of atrophy (brain parenchymal fraction, atrophy index) |  | At study entry and Months 12 and 24 | 
| Expanded Disability Status Scale (EDSS), Ambulation Index (AI), and Disease Steps (DS) scores |  | Throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment Outcome, Multiple Sclerosis, Albuterol, Copolymer 1