Treatment of Multiple Sclerosis With Copaxone and Albuterol - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator:	Autoimmunity Centers of Excellence
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00039988

Purpose

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.

Condition	Intervention
Autoimmune Diseases Multiple Sclerosis	Drug: Glatiramer acetate Drug: Albuterol Drug: Albuterol placebo

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver) Primary Purpose: Treatment
Official Title:	Treatment of Multiple Sclerosis With Copaxone (Glatiramer Acetate) and Albuterol

Resource links provided by NLM:

MedlinePlus related topics: Autoimmune Diseases Multiple Sclerosis

Drug Information available for: Albuterol Levalbuterol hydrochloride Albuterol sulfate Copolymer 1 Levalbuterol tartrate

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Change in each participant's disease status, as measured by the Multiple Sclerosis Functional Composite score (MSFC) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Glatiramer acetate-specific cytokine secretion of IL-13 cytokine secretion and IFN-gamma secretion by glatiramer acetate-reactive T-cell lines [ Time Frame: At Months 3, 6, and 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in IL-5 secretion in the supernatants of lines stimulated with glatiramer acetate [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Change in percentage of IL-12-producing monocytes by intracytoplasmic staining [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Time to first exacerbation [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Number and severity of exacerbations [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
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) [ Time Frame: At study entry and Months 12 and 24 ] [ Designated as safety issue: No ]
Expanded Disability Status Scale (EDSS), Ambulation Index (AI), and Disease Steps (DS) scores [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Enrollment:	40
Study Start Date:	November 2001
Estimated Study Completion Date:	March 2010
Primary Completion Date:	March 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Participants will receive Copaxone and albuterol placebo	Drug: Glatiramer acetate 20 mg administered subcutaneously daily Drug: Albuterol placebo Oral placebo capsules will be taken daily
Experimental: 2 Participants will receive Copaxone and albuterol	Drug: Glatiramer acetate 20 mg administered subcutaneously daily Drug: Albuterol 2 mg or 4 mg oral capsules taken daily

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00039988

Locations

United States, Massachusetts
Brigham and Women's Hospital/Harvard Medical School
Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Autoimmunity Centers of Excellence

Investigators

Principal Investigator:

Samia Khoury

More Information

No publications provided by National Institute of Allergy and Infectious Diseases (NIAID)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Khoury SJ, Healy BC, Kivisäkk P, Viglietta V, Egorova S, Guttmann CR, Wedgwood JF, Hafler DA, Weiner HL, Buckle G, Cook S, Reddy S. A randomized controlled double-masked trial of albuterol add-on therapy in patients with multiple sclerosis. Arch Neurol. 2010 Sep;67(9):1055-61.

Responsible Party:	Associate Director, Clinical Research Program, NIAID/DAIT
ClinicalTrials.gov Identifier:	NCT00039988 History of Changes
Other Study ID Numbers:	DAIT AMS01, ACE Study #AMS01
Study First Received:	June 18, 2002
Last Updated:	September 26, 2008
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Treatment Outcome
Multiple Sclerosis
Albuterol
Copolymer 1

Additional relevant MeSH terms:

Autoimmune Diseases
Multiple Sclerosis
Sclerosis
Immune System Diseases
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Pathologic Processes
Albuterol
Copolymer 1
Tocolytic Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions

Therapeutic Uses
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Adjuvants, Immunologic
Immunologic Factors
Immunosuppressive Agents

ClinicalTrials.gov processed this record on February 09, 2012