Multiple SclerosisNCT03243721
Gilenya's Impact on Cognitive Function and Thalamic Volumes
A study testing 7T MRI and Neurocognitive testing in people with Multiple Sclerosis, run by The Cleveland Clinic at 1 site in United States.
Trial summary
This evaluation will be a one-year feasibility study to characterize the neuroprotective benefits of Gilenya and its effects on cognition and grey matter volumes. The study will enroll 15 patients with relapsing-remitting multiple sclerosis being treated with Gilenya and 5 healthy controls. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- 7T MRI and Neurocognitive testing
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Oct 2017to 12 Nov 2019
- Phase
- Interventional
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- RRMS phenotype
- Treated with Gilenya for ≥6 months at the time of the baseline visit.
- Age 18-50 inclusive.
- EDSS 0-4.0
- Disease duration of 5-15 years.
- At least 12 years of education (high school diploma or general equivalency diploma).
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- Physically capable of completing neurometric testing and MRI studies.
- Age 18-50 inclusive.
- At least 12 years of education (high school diploma or general equivalency diploma)
- Physically capable of completing neurometric testing and MRI studies.
Who cannot join
- Contraindication to MRI (e.g. metal implants)
- Current use of immunomodulatory or immunosuppressant medications other than Gilenya.
- Disease of the central nervous system other than MS (e.g. Alzheimer disease, stroke, epilepsy).
- Use of anti-psychotic or psychostimulant medications. Patients started on modafinil or armodafinil more than six months prior to enrollment will not be excluded.
- Ongoing major depressive disorder that, in the opinion of the investigator, may affect cognitive functioning.
- MS relapse within 90 days of study entry.
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- Treatment with corticosteroids within 90 days of study entry.
- Current illicit substance use.
- History of alcohol or drug abuse.
- Contraindication to MRI (e.g. metal implants, claustrophobia).
- Disease of the central nervous system (e.g. MS, Alzheimer disease, stroke, epilepsy).
- Use of anti-psychotic or psychostimulant medications. Patients started on modafinil or armodafinil more than six months ago will not be excluded.
- Ongoing major depressive disorder that, in the opinion of the investigator, may affect cognitive functioning.
- Current illicit substance use.
- History of alcohol or drug abuse.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact of Gilenya on Cognitive Function and Thalamic Volume Measured by 7 Tesla MRI in Multiple Sclerosis
This evaluation will be a one-year feasibility study to characterize the neuroprotective benefits of Gilenya and its effects on cognition and grey matter volumes. The study will enroll 15 patients with relapsing-remitting multiple sclerosis being treated with Gilenya and 5 healthy controls. Each participant will undergo a battery of neurometric testing at baseline, six months, and one year. In addition, patients will undergo high-field 7T MRI at the same time points.
Read the detailed description
Cognitive impairment is a well-recognized manifestation of multiple sclerosis (MS) with prevalence estimates ranging from 43 to 70%. It is also known to occur as early as the first demyelinating event and is a major factor contributing to quality of life in MS. Treatment strategies for cognitive impairment in MS are limited. Several agents have been tested as therapeutics for MS-related cognitive dysfunction and have showed no major benefit. Cognitive rehabilitation has shown some promise, but the data are limited and many studies have suffered from methodological shortcomings. Given the lack of well-established treatment options and the substantial impact of cognitive impairment, protection of cognitive function from the earliest stages of the disease is of great importance.
Cognitive outcomes received relatively little attention in the pivotal studies of MS disease modifying therapies (DMT), but some data suggest that DMT may have a positive impact on cognition. Gilenya is of special interest because it was found to have a significant protective effect on whole brain atrophy when compared against placebo and intramuscular interferon β-1a in two phase III studies, showing a 31-35% reduction in percentage brain volume change. Gilenya's effect on whole brain atrophy leads to the natural hypothesis that it may have a beneficial effect on cognitive function in MS. Also of particular interest is the extent to which protection of the thalamus and cortex contributes to Gilenya's effect on whole brain atrophy and possible effects on cognition.
The study will enroll 15 subjects from the Cleveland Clinic Mellen Center patient population. Participants must have been on Gilenya for at least 6 months at the time of study entry. The study will involve three assessments: at baseline, six months, and one year. At each time point, participants will undergo 7T MRI of the brain with and without contrast. Participants will also undergo a battery of neurometric testing at each time point. The tests will include the Brief Visuospatial Memory Test - Revised (visuospatial skills), the iPadTM Processing Speed Test (processing speed), the Selective Reminding Test (verbal learning and memory), and the Delis-Kaplan Executive Function System Sorting Test (problem-solving skills; can only be administered at baseline and one year due to version limitations).
- Conditions
- Multiple Sclerosis
- Being tested
- 7T MRI, Neurocognitive testing
- Keywords
- multiple sclerosis, thalamus, high field MRI, cognition
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
7T MRIDiagnostic test
A high field MRI that will take approximately one hour.
Neurocognitive testingDiagnostic test
A series of tests to assess memory, verbal skills, and visuospatial skills.
| Study group | Role | What they receive |
|---|---|---|
| Gilenya treated MS patients | Experimental | Multiple sclerosis patients treated with Gilenya for at least six months. This group will receive diagnostic tests: 7T MRI and Neurocognitive testing. Receives: Diagnostic Test: 7T MRI; Diagnostic Test: Neurocognitive testing |
| Healthy controls | Experimental | Subjects without multiple sclerosis or other diseases of the central nervous system. This group will receive diagnostic tests: 7T MRI and Neurocognitive testing. Receives: Diagnostic Test: 7T MRI; Diagnostic Test: Neurocognitive testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Thalamic volume to cognitive performance
Spearman's correlation coefficient of change in thalamic volume and change in cognitive function from baseline to one year in RRMS patients treated with Gilenya.
Measured: One year.
Secondary outcomes (7)
Thalamic volume to other MRI metrics
Ratio of change in thalamic volume from baseline to six months and from baseline to one year to 1) change in brain volume (from baseline to six months and from baseline to one year); 2) change in T2 lesion volume (from baseline to six months and from baseline to one year); and 3) change in cortical thickness (from baseline to six months and from baseline to one year).
Measured: Six months and one year.
Thalamic nuclei to cognitive performance
Spearman correlation coefficient for change in the volume of each thalamic nuclei (from baseline to six months and from baseline to one year) and change in cognitive testing scores (from baseline to six months and from baseline to one year).
Measured: Six months and one year.
Thalamic myelin density to cognitive performance
Spearman correlation coefficient of change in thalamic myelin density (from baseline to six months and from baseline to one year) to change in cognitive test performance (from baseline to six months and from baseline to one year).
Measured: Six months and one year.
Thalamic axon density to cognitive performance
Spearman correlation coefficient of change in thalamic axon density (from baseline to six months and from baseline to one year) to change in cognitive test performance (from baseline to six months and from baseline to one year).
Measured: Six months and one year.
Changes in MRI metrics in Gilenya treated patients vs. controls
Ratio of change in each of the following between Gilenya treated MS patients and healthy controls: 1.) Thalamic volume change (from baseline to six months and from baseline to one year); 2) Cortical thickness change (from baseline to six months and from baseline to one year); 3) thalamic axon density change (from baseline to six months and from baseline to one year); 4) thalamic myelin density (from baseline to six months and from baseline to one year).
Measured: Six months and one year.
Changes in cognitive performance in Gilenya treated patients vs controls
Ratio of change in cognitive test performance (from baseline to six months and from baseline to one year) between Gilenya treated patients and controls.
Measured: Six months and one year.
Thalamic volume to cognitive performance
Spearman's correlation coefficient of change in thalamic volume and change in cognitive function from baseline to six months in RRMS patients treated with Gilenya.
Measured: Six months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2017
- Study start20 Oct 2017
- Primary completion12 Nov 2019
- Study completion12 Nov 2019
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.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- There will be two groups running in parallel. One will be MS patients (15) and the other will be control patients (5). Both groups will receive the same interventions.
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Principal investigator, Devon Conway MD, The Cleveland Clinic
- Investigators
- Devon S Conway, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03243721
- Sponsor's protocol ID
- CCF 17-766
- Status last verified
- Sep 2021
- First submitted
- 1 Aug 2017
- Last updated
- 5 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The data will be analyzed in aggregate. There is no plan to share individual participant data with other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Gilenya on Cognitive Function and Thalamic Volume Measured by 7 Tesla MRI in Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT03243721
- Acronym / sponsor ID
- CCF 17-766
- Conditions
- Multiple Sclerosis
- Keywords
- multiple sclerosis, thalamus, high field MRI, cognition
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- 20 Oct 2017 (actual)
- Primary completion
- 12 Nov 2019 (actual)
- Study completion
- 12 Nov 2019 (actual)
- First posted
- 9 Aug 2017 (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.
This evaluation will be a one-year feasibility study to characterize the neuroprotective benefits of Gilenya and its effects on cognition and grey matter volumes. The study will enroll 15 patients with relapsing-remitting multiple sclerosis being treated with Gilenya and 5 healthy controls. Each participant will undergo a battery of neurometric testing at baseline, six months, and one year. In addition, patients will undergo high-field 7T MRI at the same time points.
Detailed description
Cognitive impairment is a well-recognized manifestation of multiple sclerosis (MS) with prevalence estimates ranging from 43 to 70%. It is also known to occur as early as the first demyelinating event and is a major factor contributing to quality of life in MS. Treatment strategies for cognitive impairment in MS are limited. Several agents have been tested as therapeutics for MS-related cognitive dysfunction and have showed no major benefit. Cognitive rehabilitation has shown some promise, but the data are limited and many studies have suffered from methodological shortcomings. Given the lack of well-established treatment options and the substantial impact of cognitive impairment, protection of cognitive function from the earliest stages of the disease is of great importance.
Cognitive outcomes received relatively little attention in the pivotal studies of MS disease modifying therapies (DMT), but some data suggest that DMT may have a positive impact on cognition. Gilenya is of special interest because it was found to have a significant protective effect on whole brain atrophy when compared against placebo and intramuscular interferon β-1a in two phase III studies, showing a 31-35% reduction in percentage brain volume change. Gilenya's effect on whole brain atrophy leads to the natural hypothesis that it may have a beneficial effect on cognitive function in MS. Also of particular interest is the extent to which protection of the thalamus and cortex contributes to Gilenya's effect on whole brain atrophy and possible effects on cognition.
The study will enroll 15 subjects from the Cleveland Clinic Mellen Center patient population. Participants must have been on Gilenya for at least 6 months at the time of study entry. The study will involve three assessments: at baseline, six months, and one year. At each time point, participants will undergo 7T MRI of the brain with and without contrast. Participants will also undergo a battery of neurometric testing at each time point. The tests will include the Brief Visuospatial Memory Test - Revised (visuospatial skills), the iPadTM Processing Speed Test (processing speed), the Selective Reminding Test (verbal learning and memory), and the Delis-Kaplan Executive Function System Sorting Test (problem-solving skills; can only be administered at baseline and one year due to version limitations).
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- There will be two groups running in parallel. One will be MS patients (15) and the other will be control patients (5). Both groups will receive the same interventions.
| Arm | Type | Receives |
|---|---|---|
| Gilenya treated MS patients | Experimental | Diagnostic Test: 7T MRI, Diagnostic Test: Neurocognitive testingMultiple sclerosis patients treated with Gilenya for at least six months. This group will receive diagnostic tests: 7T MRI and Neurocognitive testing. |
| Healthy controls | Experimental | Diagnostic Test: 7T MRI, Diagnostic Test: Neurocognitive testingSubjects without multiple sclerosis or other diseases of the central nervous system. This group will receive diagnostic tests: 7T MRI and Neurocognitive testing. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- RRMS phenotype
- Treated with Gilenya for ≥6 months at the time of the baseline visit.
- Age 18-50 inclusive.
- EDSS 0-4.0
- Disease duration of 5-15 years.
Key exclusion criteria (15 listed)
- Contraindication to MRI (e.g. metal implants)
- Current use of immunomodulatory or immunosuppressant medications other than Gilenya.
- Disease of the central nervous system other than MS (e.g. Alzheimer disease, stroke, epilepsy).
- Use of anti-psychotic or psychostimulant medications. Patients started on modafinil or armodafinil more than six months prior to enrollment will not be excluded.
- Ongoing major depressive disorder that, in the opinion of the investigator, may affect cognitive functioning.
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 |
|---|---|---|
| 7T MRIA high field MRI that will take approximately one hour. | Diagnostic test | Gilenya treated MS patients, Healthy controls |
| Neurocognitive testingA series of tests to assess memory, verbal skills, and visuospatial skills. | Diagnostic test | Gilenya treated MS patients, Healthy controls |
Primary outcome
Thalamic volume to cognitive performance
Time frame: One year.
Spearman's correlation coefficient of change in thalamic volume and change in cognitive function from baseline to one year in RRMS patients treated with Gilenya.
7 secondary outcomes
Thalamic volume to other MRI metrics
Time frame: Six months and one year.
Thalamic nuclei to cognitive performance
Time frame: Six months and one year.
Thalamic myelin density to cognitive performance
Time frame: Six months and one year.
Thalamic axon density to cognitive performance
Time frame: Six months and one year.
Changes in MRI metrics in Gilenya treated patients vs. controls
Time frame: Six months and one year.
Changes in cognitive performance in Gilenya treated patients vs controls
Time frame: Six months and one year.
Thalamic volume to cognitive performance
Time frame: Six months.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2021.
- Individual participant dataSharing planned: No. The data will be analyzed in aggregate. There is no plan to share individual participant data with other 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.
Devon S Conway, MD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 7T MRI and Neurocognitive testing in people with Multiple Sclerosis, run by The Cleveland Clinic 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 10 inclusion and 15 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: finished, as of the sponsor's last update on 5 Sep 2021. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Thalamic volume to cognitive performance (time frame: One 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 5 Sep 2021.