Glatiramer Acetate for Multiple Sclerosis With Autoimmune Comorbidities
|ClinicalTrials.gov Identifier: NCT01456416|
Recruitment Status : Completed
First Posted : October 20, 2011
Last Update Posted : April 4, 2013
|Condition or disease||Phase|
|Relapsing Remitting Multiple Sclerosis||Phase 4|
Multiple Sclerosis (MS) is an auto-immune neurodegenerative disease that affects more than 400,000 individuals in the United States, and 2.5 million worldwide (www.nationalmssociety.org). The main pathogenic mechanism in MS involves an inflammatory condition that damages the myelin of the central nervous system (CNS), resulting in axonal damage and neurological impairment, often leading to severe disability. MS is one of the most common causes of neurological disability in young and middle-aged adult individuals, and as such has a tremendous physical, psychological and social impact on patients' lives. MS is a complex disease diagnosed by McDonald criteria with different clinical and pathological phenotypes. Several forms of MS have been described: Relapsing-Remitting (RRMS), Secondary-Progressive MS (SPMS), Progressive-Relapsing MS (PRMS), and Primary-Progressive MS (PPMS).
Glatiramer Acetate (GA) and Beta-Interferons (β-IFNs) are well established first-line immunomodulating treatment options for relapsing remitting multiple sclerosis (RRMS) with excellent safety profiles. The mechanisms of action of GA and IFNs are different. It is well known that in general Disease-Modifying Treatments (DMTs) reduce relapse rate in more than half of the multiple sclerosis (MS) patients who receive DMT, while having little if any effect on the rest. It has been speculated that the response to beta-interferons or GA may have genetic basis. As Axtell RC et al. indicated the experimental autoimmune encephalomyeilits (EAE) in mouse caused by TH1 cells generally respond well to interferon-beta, while EAE caused by TH17 cells get worse with interferon-beta.
Autoimmune disease is an extreme situation where the autoimmune response overshoots and goes out of control. The other extreme is a degenerative disorder, where the autoimmune response is not strong enough for effective protection, and degeneration therefore continues. GA being an immunomodulator may provide both properly regulated immune suppression (in the case of autoimmune disease) and properly regulated immune activation (in the case of the neurodegenerative disease).
Autoimmune conditions cluster in families with high risk for multiple sclerosis than in general population which suggests that the disease might arise on a background of a generalized susceptibility to autoimmunity. Occurrence of psoriasis, autoimmune thyroiditis, vasculitis, rheumatoid arthritis, scleroderma, lupus are seen more commonly in MS patients. Many of these patients initially get started on beta-IFNs, and usually do not do well on them. According to Investigator's and the USC MS Comprehensive Care Center experience, autoimmune co-morbidity associated with MS can serve as a biological marker predicting good response to GA and unfavorable response to the IFNs.
|Study Type :||Observational|
|Actual Enrollment :||10 participants|
|Official Title:||Pilot Study for Evaluation of Glatiramer Acetate in RRMS Patients With Comorbid Autoimmune Conditions|
|Study Start Date :||September 2011|
|Primary Completion Date :||April 2013|
|Study Completion Date :||April 2013|
U.S. FDA Resources
GA administered SQ daily in MS patients who met all Inclusion-Exclusion Criteria and were approved by their Health Care Plans for GA treatment.
- Change from Baseline in Clinical Global Impression Scale (CGI-1). [ Time Frame: Comparison of CGI-1 score pre- and post-treatment.at 6 months. ]The primary objective is to determine whether daily GA injections do not aggravate comorbid autoimmune conditions.
- Secondary objectives include Visual Analog Scale (VAS). [ Time Frame: Secondary objective will be done at Baseline, Mo 3, Mo 6. ]Comparison of VAS data pre- and post-treatment (Baseline, Mo 3, Mo 6).
- Secondary objectives include Expanded Disability Status Scale (EDSS) [ Time Frame: Secondary objective will be done at Baseline, Mo 3, Mo 6. ]Comparison of EDSS score pre- and post-treatment (Baseline, Mo 3, Mo 6).
- Secondary objectives include concomitant medication review. [ Time Frame: Secondary objective will be done at Baseline, Mo 3, Mo 6. ]Comparison/review of Concomitant Medications used for co-morbid condition treatment (Baseline, Mo 3, Mo 6).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01456416
|United States, California|
|USC MS Comprehensive Care Center & Research Group|
|Los Angeles, California, United States, 90033|
|Principal Investigator:||Regina Berkovich, M.D.Ph.D||LAC+USC|