EARLY IFNb-1a and Atorvastatin Combination Therapy of Isolated Clinical Syndrome Suggestive of Multiple Sclerosis

EARLY IFNb-1a (Rebif) and Atorvastatin (Lipitor) Combination Therapy of Isolated Clinical Syndrome Suggestive of Multiple Sclerosis

The primary purpose is to determine the changes in gene expression induced by IFNb-1a (Rebif) and atorvastatin (Lipitor) combination therapy in patients with an isolated clinical syndrome suggestive of multiple sclerosis (MS), to identify markers of therapeutic response, and to predict patients' clinical response based on their in vitro response to this combination therapy measured by the gene expression levels in activated peripheral blood mononuclear cells (PBMCs).

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Rebif

Detailed Description

Multiple Sclerosis (MS) is a chronic neurologic disease, characterized pathologically by focal areas of inflammation, demyelination, axonal injury and degeneration in the central nervous system. MS follows several different disease courses. Approximately, 90% of patients have a relapsing form of the disease. We propose that atorvastatin (Lipitor) may enhance the immunomodulatory effects of INFb-1a (Rebif) in patients with clinically isolated neurological syndrome suggestive of MS. This combination may be more effective in preventing development of definitive relapsing-remitting MS if administered early in the course of the disease. The study will identify markers of disease activity that are selectively affected by this combination therapy. Identified markers may be used in future clinical trials to predict patient's clinical response and to monitor the response to treatment as a secondary outcome measure.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina-Chapel Hill MS Clinic Within the Neuroscience Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with isolated clinical syndrome suggestive of MS

• At least three out of four magnetic resonance imaging (MRI) findings on the initial scan:

  • One Gd-enhancing lesion or nine T2 hyperintense lesions;
  • At least one infratentorial lesion;
  • At least one juxtacortical lesion; and
  • At least three periventricular lesions.
• Expanded Disability Status Scale (EDSS) 0-5.5
• 18 to 60 years of age
• At least one relapse in previous 12 months

Exclusion Criteria:

• Patients with a diagnosis of clinically definitive relapsing-remitting (RR) MS, secondary progressive, or primary progressive MS.
• Patients who have ever been treated with mitoxantrone, cytoxan, cyclophosphamide, or total lymphoid irradiation (TLI).
• Patients treated with IFNb-1a, IFNb-1b, glatiramer acetate, intravenous immunoglobulins (IVIg), plasma exchange, methotrexate, or azathioprine in the previous 3 months.
• Patients treated with intravenous or oral steroids within 30 days prior to baseline MRI.
• Patients who have been treated with statins in the previous 3 months.
• Pregnant or breast-feeding women.
• Patients with a history of severe cardiac, hepatic, pulmonary, gastrointestinal, or renal disease.
• Abnormal baseline blood tests including alanine transaminase (ALT) or aspartate transaminase (AST) greater than twice the upper limit of normal

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rebif + Lipitor	Drug: Rebif; Rebif 44mcg TIW

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the effects of IFNb-1a plus atorvastatin versus IFNb-1a plus placebo on the gene expression in peripheral blood mononuclear cells (PBMCs) derived from patients with isolated clinical syndrome suggestive of MS	2 years
To identify markers of therapeutic response and to predict patients' clinical response based on their in vitro response to this combination therapy measured by the gene expression levels in activated PBMCs	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
evaluate safety and efficacy of combination therapy with Rebif and Lipitor in patients with clinicayy isolated syndrome suggestive of MS.	2 years

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Investigators: Principal Investigator: Silva Markovic-Plese, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: August 26, 2005
• First Submitted That Met QC Criteria: August 26, 2005
• First Posted (Estimate): August 29, 2005

Study Record Updates

• Last Update Posted (Estimate): June 23, 2009
• Last Update Submitted That Met QC Criteria: June 22, 2009
• Last Verified: June 1, 2009

More Information

Terms related to this study

• Keywords: Clinically Isolated Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: 04-NEUR-293