Assessing the Cognitive Benefits of Ozanimod and Their Brain-Biomarkers in MS

NCT ID: NCT06334094

Last Updated: 2024-08-09

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-06-01
• Study Completion Date: 2028-05-31

Brief Summary

The primary objective of this study is to investigate the cognitive benefits of ozanimod in individuals with Multiple Sclerosis (MS). The study aims to understand the neural basis of cognitive improvement in Relapsing-Remitting MS patients under ozanimod treatment using neuroimaging and behavioral techniques to characterize the brain and behavioral changes due to ozanimod treatment.

Detailed Description

To assess MS patients' cognitive improvement while on ozanimod, the investigators will compare MS patients' baseline performance to the patients' performance following treatment on memory, processing speed, verbal ability and executive function. The investigators predict that cognitive performance will improve during the ozanimod treatment compared to the baseline. Baseline-treatment differences will be assessed using repeated-measures analysis of covariance (ANCOVA) while also controlling for effects of age, education, disease duration, and expanded disability status score (EDSS). The investigators predict that improved cognitive performance will be accompanied by improvements in brain structure (e.g., increased whole brain volume) and function metrics.

Thus, each MS patients' brain volume, white matter connectivity, lesion load, and resting BOLD at baseline, during treatment, and after ozanimod treatment will be measured. For each structure and function MR metric, baseline-treatment differences will be assessed using repeated-measures ANCOVA while also controlling for effects of age, education, disease duration, EDSS and brain parenchymal fraction (the ratio of functional brain tissue to whole brain volume).

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ozanimod

Participants will receive Ozanimod and work up to .92 mg. They will then take one pill daily for a duration of 12 months.

Group Type: EXPERIMENTAL

Ozanimod

Intervention Type: DRUG

A hard capsule that is taken daily for one year.

Interventions

Ozanimod

A hard capsule that is taken daily for one year.

Intervention Type: DRUG

Other Intervention Names

Zeposia

Eligibility Criteria

Inclusion Criteria

1. English-speaking Relapsing-Remitting MS (RRMS; intermittent symptom exacerbations followed by periods of remission) patients.

2. Male and female, between the ages of 18-55 years old will be recruited from the Texas Institute for Neurological Disorders (TIND) and MS Clinic of The University of Texas Southwestern. Study referrals will come from board-certified neurologists.

3. Patients will have a McDonald-criteria diagnosis of RRMS, be >30 days past exacerbation and corticosteroid treatment.

4. Included patients will also be free of substance abuse and significant medical, other neurological, or psychiatric conditions unrelated to their MS disease course.

5. Patient selection will be limited to patients that are treatment naïve (i.e., have not been previously treated for their MS) or require a change in treatment course.

6. A clinical determination is needed as to whether ozanimod is the best treatment for a patient or whether a patient requires treatment change to ozanimod.

7. All included participants will be right-handed and at least high-school educated.

8. Only patients who score above 25 on the Telephone Interview for Cognitive Status (TICS) will be included.

Exclusion Criteria

1. During calibrated functional magnetic resonance imaging (fMRI) scanning, participants will inhale a carbon dioxide/room air solution to allow for calibration of BOLD signal. Thus, to ensure participant safety, the investigators exclude: smokers and those with MR-contraindicators, any participants with a history of respiratory or pulmonary problems (e.g., asthma, Chronic Obstructive Pulmonary Disease (COPD), sarcoidosis, tuberculosis), any participant with a history of cerebral vascular disease (e.g., cardiac disease, transient ischemic attack, migraines, stroke, arteriovenous malformation), any participant with a history of respiratory or pulmonary problems (e.g., asthma, Chronic Obstructive Pulmonary Disease (COPD), sarcoidosis, tuberculosis), and any participant with a history of cerebral vascular disease (e.g., cardiac disease, transient ischemic attack, migraines, stroke, arteriovenous malformation).

2. Participants that present with EKG abnormalities consistent with FDA labeling contained within the ozanimod guidelines will be excluded as these abnormalities may be indication of dangerous negative side effects upon ozanimod consumption. EKG abnormalities include presence of atrioventricular (AV) block, sick sinus syndrome, or sino-atrial block. Any experiences of myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or Class III or IV heart failure within the last 6 months will exclude the patient. Contraindicators of ozanimod that may be found in the blood sample include presence of varicella titers and enzyme/protein levels that indicate liver dysfunction. Thus, these participants will be excluded.

3. Patients who exhibit diseases other than MS that may be responsible for the patient's clinical, or MRI presentation will be excluded.

4. Patients who exhibit a history of hypersensitivity to ozanimod or any drugs of similar chemical classes (i.e., sphingosine phosphates) will be excluded.

5. Female participants who are pregnant or nursing will be excluded from the study. After the participant consents to being in the study, there will be a screening appointment to determine their eligibility, at which a pregnancy test will be provided. Other examinations, such as neurological assessments and EKGs, will occur at this appointment.

6. Patients who are not native-English speakers will be excluded, as their English ability may limit their understanding of the instructions and performance on the neuropsychological tests.

7. Patients who score below 25 on the Telephone Interview for Cognitive Status (TICS) will be excluded.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Texas Institute for Neurological Disorders

UNKNOWN

Sponsor Role: collaborator

The University of Texas at Dallas

OTHER

Sponsor Role: lead

Responsible Party

Dr. Bart Rypma

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bart Rypma, PhD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas at Dallas

Locations

Center for Brain Health

Dallas, Texas, United States

Countries

United States

Other Identifiers

IM047-1054

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

IRB-23-486

Identifier Type: -

Identifier Source: org_study_id