This is an open-label, single-blinded, observational, prospective, 24 months follow-up, controlled study to assess the efficacy of Gilenya on thalamus pathology and cognitive impairment in 30 relapsing MS patients naïve to Gilenya who fulfilled the inclusion and exclusion criteria used for screening and started Gilenya, on a clinical basis. In addition, 20 HCs will be included as a reference population. Because this is an observational study investigating evolution of thalamic atrophy, iron deposition, cognitive dysfunction and response to herpes viruses in patients treated with Gilenya on a clinical basis the patients are not starting Gilenya as an investigational drug. Therefore, the patients who are already started Gilenya by the treatment decision of their physician will be asked to participate in this observational study.
The screening and starting procedures criteria for Gilenya on a clinical basis and for our study are defined by the Gilenya PI. All patients in our clinic have standardized assessments before starting any disease-modifying therapy. Once the patient decided to start Gielnya on a clinical basis and qualified on a screening, as defined by Gilenya PI, our team will be informed and contact the patient regarding participation in the present study before receiving first dose of Gilenya. Once the informed consent is signed, the patient will follow study procedures, as outlined in the protocol and study evaluation schedule. All subjects will be assessed at 0, 6, 12 and 24 months with the same clinical, 3T MRI and laboratory, and humoral response to herpes viruses examinations. The cognitive assessments and evaluation of environmental risk factors will be performed at 0, 12 and 24 months. Safety will be also assessed at 0, 6, 12 and 24 months of the study.
The healthy controls (HC) will serve as reference comparison group to patients for atrophy iron, cognitive and response to herpesvirus outcomes. We considered alternative study designs as listed below. The head-to-head comparison with untreated or comparator-treated patients are difficult to conduct and can not be performed without proper randomization and double-blinding which is costly and unfeasible in mechanistical study like is the one proposed. The inclusion of a HC group provides a valuable baseline, allowing evaluation of the proposed techniques for normal variation between individuals, against which changes in the proposed outcomes could be compared. Use of HCs for comparison with a patient population in prospective longitudinal pilot studies of non-conventional MRI, including measurement of thalamic atrophy and iron deposition, may become an attractive approach in the future for several reasons. First, the ultimate goal of therapy is to normalize patient changes over time, to those observed in HCs over the same time period. HCs also experience brain changes over time and so the notion of arresting disease progression as measured by proposed outcomes requires validation by reference to a comparator without disease progression to account for age-related changes. Second, ethical considerations preclude placebo-controlled studies using an established MS treatment versus placebo-treatment in patients with RRMS.
The MRI analysis will be performed fully blinded, as are all phase I, II, III and IV trials calculated at the Buffalo Neuroimaging Analysis Center (BNAC), Buffalo, NY. BNAC has been involved as an centralized MRI reading center in many MS clinical trials that included over 500 sites around the world in 55 countries The detailed procedures of how the MRI DICOM files are blinded and how the workload is distributed are part of our internal standard operating procedures (SOPs) that have been accepted as appropriate following standard audits by government and industry agencies.
All participants will undergo study eligibility screening and consenting by a Clinical Research Project Coordinator. The participant will be provided with a description of the required testing for study participation, and any risks will be described in order for the person to make an informed decision regarding voluntary study participation. This is also an opportunity for the person to ask questions regarding the study and the testing components. All study participants who choose to enroll in the study will be asked to sign and date the consent form in front of the Study Coordinator who will also sign and date the consent as witness.
