Multiple SclerosisPhase 4NCT06334094
Assessing the Cognitive Benefits of Ozanimod and Their Brain-Biomarkers in MS
A Phase 4 study testing Ozanimod in people with Multiple Sclerosis, run by The University of Texas at Dallas at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Ozanimod
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2024to 31 May 2028
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- English-speaking Relapsing-Remitting MS (RRMS; intermittent symptom exacerbations followed by periods of remission) patients.
- 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.
- Patients will have a McDonald-criteria diagnosis of RRMS, be >30 days past exacerbation and corticosteroid treatment.
- Included patients will also be free of substance abuse and significant medical, other neurological, or psychiatric conditions unrelated to their MS disease course.
- 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.
- 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.
- All included participants will be right-handed and at least high-school educated.
- Only patients who score above 25 on the Telephone Interview for Cognitive Status (TICS) will be included.
Who cannot join
- 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).
- 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.
- Patients who exhibit diseases other than MS that may be responsible for the patient's clinical, or MRI presentation will be excluded.
- Patients who exhibit a history of hypersensitivity to ozanimod or any drugs of similar chemical classes (i.e., sphingosine phosphates) will be excluded.
- 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.
- 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.
- Patients who score below 25 on the Telephone Interview for Cognitive Status (TICS) will be excluded.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- Ozanimod
- Keywords
- Zeposia, Ozanimod
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OzanimodDrug
Also called Zeposia
A hard capsule that is taken daily for one year.
| Study group | Role | What they receive |
|---|---|---|
| Ozanimod | Experimental | Participants will receive Ozanimod and work up to .92 mg. They will then take one pill daily for a duration of 12 months. Receives: Drug: Ozanimod |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Processing Speed/Symbol-Digit Modality Test (SDMT) Performance
SDMT is a neuropsychological assessment of processing speed in MS. The SDMT consists of 9 symbols that correspond to a number. Participants have 90 seconds to complete as many symbol to number associations as they can. Scoring is based on how many they can complete correctly in the span of 90 seconds. Therefore, to assess MS patients' cognitive changes while on ozanimod, MS patients' baseline performance to their performance following treatment on processing speed will be compared. The primary endpoint for this study will be a change from baseline in written SDMT performance of at least 4 points.
Measured: 1 year
Secondary outcomes (5)
Change in Volumetric Blood-Oxygen-Level-Dependent (BOLD) signal as Measured by Dual Echo Functional Magnetic Resonance Imaging (fMRI)
To assess the mechanisms by which ozanimod changes processing speed in MS, fMRI measures will be obtained, including the patients' volumetric BOLD signal. To assess metrics of MS patients' structural and functional changes while on ozanimod, MS patients' resting BOLD will be measured. In the context of the within-subjects design, comparisons will be performed between each of the MS patients to themselves by comparing their baseline and treatment-assessment MR metrics. Each MS patients' resting BOLD signal will be measured at baseline, during treatment, and after ozanimod treatment. Additionally, BOLD signal of ozanimod-responders to non-responders will be compared.
Measured: 1 year
Change in Cerebral Blood Flow (CBF) as Measured by Dual Echo Functional Magnetic Resonance Imaging (fMRI)
To assess metrics of MS patients' neurophysiology changes while on ozanimod compared to baseline, MS patients' CBF during the treatment phase will be assessed for comparison to baseline. In the context of the within-subjects design, comparisons will be performed between each of the MS patients to themselves by comparing their baseline and treatment-assessment MR metrics.
Measured: 1 year
Change in Cerebral Metabolic Rate of Oxygen (CMRO2) as Measured by Dual Echo Functional Magnetic Resonance Imaging (fMRI)
To assess metrics of MS patients' neurophysiology changes while on ozanimod compared to baseline, MS patients' CMRO2 and CBF/CMRO2 ratio (i.e., NVC) will be assessed during the treatment phase for comparison to baseline. In the context of the within-subjects design, comparisons will be performed between each of the MS patients to themselves by comparing their baseline and treatment-assessment MR metrics.
Measured: 1 year
Change in Whole Brain Volume as Measured By Structural Magnetic Resonance Imaging
To assess metrics of MS patients' structural and functional changes while on ozanimod, the investigators will measure MS patients' brain volume. In the context of the within-subjects design, comparisons will be performed between each of the MS patients to themselves by comparing their baseline and treatment-assessment MR metrics.
Measured: 1 year
Differences in Diffusion parameters of ozanimod-responders to non-responders as Measured By a Diffusion Kurtosis Resonance Imaging (DKI)
To assess metrics of MS patients' neurophysiology changes while on ozanimod compared to baseline, MS patients' diffusion parameters of ozanimod-responders to non-responders will be assessed.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2024
- Study start1 Jun 2024 (estimated)
- Primary completion31 Mar 2028 (estimated)
- Study completion31 May 2028 (estimated)
Why it stopped: The funding for the study was revoked. As such, the study is no longer being conducted.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Texas at Dallas
- Sponsor type
- University, hospital or other
- Collaborators
- Texas Institute for Neurological Disorders
- Responsible party
- Principal investigator, Dr. Bart Rypma, The University of Texas at Dallas
- Investigators
- Bart Rypma, PhD, Principal investigator, The University of Texas at Dallas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06334094
- Sponsor's protocol ID
- IRB-23-486
- Other IDs
- IM047-1054
- Status last verified
- Aug 2024
- First submitted
- 26 Feb 2024
- Last updated
- 9 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be shared with BMS researchers.
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing the Cognitive Benefits of Ozanimod and Their Brain-Biomarkers in MS
- ClinicalTrials.gov ID
- NCT06334094
- Acronym / sponsor ID
- IRB-23-486
- Conditions
- Multiple Sclerosis
- Keywords
- Zeposia, Ozanimod
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The funding for the study was revoked. As such, the study is no longer being conducted.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- The University of Texas at DallasUniversity, hospital or other
- Collaborators
- Texas Institute for Neurological Disorders
- Study start
- 1 Jun 2024 (estimated)
- Primary completion
- 31 Mar 2028 (estimated)
- Study completion
- 31 May 2028 (estimated)
- First posted
- 27 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ozanimod | Experimental | Drug: OzanimodParticipants will receive Ozanimod and work up to .92 mg. They will then take one pill daily for a duration of 12 months. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- English-speaking Relapsing-Remitting MS (RRMS; intermittent symptom exacerbations followed by periods of remission) patients.
- 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.
- Patients will have a McDonald-criteria diagnosis of RRMS, be >30 days past exacerbation and corticosteroid treatment.
- Included patients will also be free of substance abuse and significant medical, other neurological, or psychiatric conditions unrelated to their MS disease course.
- 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.
Key exclusion criteria (7 listed)
- 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).
- 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.
- Patients who exhibit diseases other than MS that may be responsible for the patient's clinical, or MRI presentation will be excluded.
- Patients who exhibit a history of hypersensitivity to ozanimod or any drugs of similar chemical classes (i.e., sphingosine phosphates) will be excluded.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OzanimodAlso: ZeposiaA hard capsule that is taken daily for one year. | Drug | Ozanimod |
Primary outcome
Change in Processing Speed/Symbol-Digit Modality Test (SDMT) Performance
Time frame: 1 year
SDMT is a neuropsychological assessment of processing speed in MS. The SDMT consists of 9 symbols that correspond to a number. Participants have 90 seconds to complete as many symbol to number associations as they can. Scoring is based on how many they can complete correctly in the span of 90 seconds. Therefore, to assess MS patients' cognitive changes while on ozanimod, MS patients' baseline performance to their performance following treatment on processing speed will be compared. The primary endpoint for this study will be a change from baseline in written SDMT performance of at least 4 points.
5 secondary outcomes
Change in Volumetric Blood-Oxygen-Level-Dependent (BOLD) signal as Measured by Dual Echo Functional Magnetic Resonance Imaging (fMRI)
Time frame: 1 year
Change in Cerebral Blood Flow (CBF) as Measured by Dual Echo Functional Magnetic Resonance Imaging (fMRI)
Time frame: 1 year
Change in Cerebral Metabolic Rate of Oxygen (CMRO2) as Measured by Dual Echo Functional Magnetic Resonance Imaging (fMRI)
Time frame: 1 year
Change in Whole Brain Volume as Measured By Structural Magnetic Resonance Imaging
Time frame: 1 year
Differences in Diffusion parameters of ozanimod-responders to non-responders as Measured By a Diffusion Kurtosis Resonance Imaging (DKI)
Time frame: 1 year
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2024.
- Individual participant dataSharing planned: Yes. Data will be shared with BMS researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bart Rypma, PhD principal investigator
The University of Texas at Dallas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ozanimod in people with Multiple Sclerosis, run by The University of Texas at Dallas at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 9 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Processing Speed/Symbol-Digit Modality Test (SDMT) Performance (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2024.