The overall aim of the proposed project is to investigate the potential re-purposing of the commonly used blood pressure treatment, lisinopril, for the treatment of patients with Relapsing Remitting Multiple Sclerosis (RRMS) using a highly novel approach to clinical trial execution that leverages today's IT and telemonitoring technology. Researchers in two independent US and EU laboratories found that modulators of the renin-angiotensin-aldosterone system (RAAS), including Angiotensin Converting Enzyme (ACE) inhibitors such as lisinopril) are effective in delaying or reversing the course of "disease" in the experimental autoimmune encephalomyelitis (EAE) rodent model of MS. Furthermore, Dr. Lawrence Steinman's team at Stanford University also discovered that key RAAS elements are found and up-regulated at the site of disease in brain samples from MS patients. Due to its well-defined safety profile from use in millions of patients worldwide, lisinopril represents a low-risk opportunity to test the "re-purposing" hypothesis that ACE inhibitors are effective treatments for MS. Re-purposing of marketed drugs or those agents whose development has been abandoned in their original indication, is a growing area of interest in drug development, where the ever-increasing cost of clinical trials has led to the shelving of hundreds of development agents because of heightened financial risk. In the proposed study, novel methodology and remote monitoring techniques will be developed and used for collection of over 90% of the study data, dramatically reducing the cost of the trial by minimizing in-person visits and interactions with healthcare professionals. In Phase 1 of this fast track application will be used to develop and validate the novel data collection methods to be used in the lisinopril trial, including administration of the MS Functional Composite test by remote video and the use the "MAPS" (Movement and Activity in Physical) protocol via telemonitoring. The study is a randomized, double-blind, placebo controlled, parallel group design evaluating 12 months treatment with 20 or 40 mg lisinopril or placebo in 180 patients with RRMS who are currently taking an interferon beta therapy. The primary endpoint will be the Multiple Sclerosis Functional Composite score; secondary endpoints will include the Expanded Disability Status Scale, MAPS, MSQOL 54, Krupp Fatigue Severity Scale and the Change in Comprehensive Assessment of MS Symptoms. Patient satisfaction with the novel technologies and telemonitoring approach will be assessed, to enable future improvements.
Public Health Relevance Statement: Public Health Relevance: This is an application to test whether lisinopril, a low-cost and generally safe generic drug, can help reduce the symptoms of multiple sclerosis. If successful, it will add an important new drug to the existing therapeutic mix that can improve the quality and reduce the cost of treatment for this devastating disease. We propose a number of methodological innovations to clinical trial design and execution that will decrease cost, maintain data integrity and preserve rigorous design elements of randomized controlled trials. If proven feasible, these innovations will be generalizable to a broad spectrum of clinical trials.
Project Terms: Adverse effects; Angiotensin-Converting Enzyme Inhibitors; Animal Model; Area; Autoimmunity; base; Beryllium; Blood Pressure; Brain; Cessation of life; Client satisfaction; clinical research site; Clinical Trials; Clinical Trials Design; Collection; cost; Crowding; Data; Data Collection; data integrity; Data Quality; Databases; design; Development; Devices; disability; Disease; Disorder by Site; Double-Blind Method; Drug Costs; drug development; drug market; effective therapy; Effectiveness; Electronics; Elements; Enrollment; Enzyme Inhibition; Experimental Autoimmune Encephalomyelitis; Failure (biologic function); Fatigue; FDA approved; functional status; Future; Generic Drugs; Goals; Health Professional; Home environment; improved; Information Technology; innovation; Institutional Review Boards; instrument; interest; interferon therapy; Interferon-beta; Internet; Intervention Studies; Investments; Laboratories; Lisinopril; Maps; Marketing; Measures; medication compliance; meetings; Methodology; Methods; Monitor; Movement; Multiple Sclerosis; Mus; National Heart, Lung, and Blood Institute; National Institute of Mental Health (U.S.); new technology; novel; novel strategies; Nurses; Paralysed; Participant; Patient Outcomes Assessments; Patient-Focused Outcomes; Patients; Peptidyl-Dipeptidase A; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase II Clinical Trials; Placebo Control; Placebos; Play; Positioning Attribute; pre-clinical; programs; prospective; Protocols documentation; public health relevance; Randomized; Randomized Controlled Trials; randomized trial; Regulatory T-Lymphocyte; Relapsing-Remitting Multiple Sclerosis; Renin-Angiotensin-Aldosterone System; Research Design; Research Infrastructure; Research Personnel; Resources; response; Rewards; Risk; Rodent Model; Role; Safety; Sampling; Secure; Severities; Site; Site Visit; Small Business Innovation Research Grant; Surveys; Symptoms; Techniques; Technology; Testing; Text; Therapeutic; Training; Treatment Cost; Universities; Visit; Voice
