Plain English Summary
Background and study aims
Multiple sclerosis (MS) is one of the most common diseases of the central nervous system (brain and spinal cord). Healthy nerves are coated in a fatty casing (myelin sheath) which helps messages to travel quickly and smoothly along nerves. When a person is suffering from MS, the immune system, which normally helps to protect against infection, attacks the myelin sheath, stripping it from the nerves (demyelination). This demyelination means that messages cannot travel along the nerves effectively, causing a range of disturbances including loss of vision, problems with balance and coordination and weakness in the arms or legs. At first, the body is able to rebuild the myelin sheath (remyelination) but as the disease progresses to the secondary phase (secondary progressive MS), this process fails and the nerves themselves break down (neurodegeneration), ultimately leading to paralysis and death. One of the most important parts of treatment is delaying the onset of secondary progressive MS as long as possible. Around 85% of MS sufferers are diagnosed with the relapsing remitting type. This is where the sufferer has sudden flare-ups of symptoms (relapses) followed by periods where the symptoms are very mild or disappear completely. The anti-cancer drug bexarotene has shown that it can actually help to encourage remyelination in animal studies. The aim of this study is to find out whether treatment with bexarotene can help to promote remyelination in humans suffering from relapsing remitting MS.
Who can participate?
Adults between 30 and 50 years old who are suffering from relapsing remitting MS.
What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group are given bexarotene capsules to take for nine months. Those in the second group are given a placebo (dummy pill) to take for the same length of time. During the nine month study period, participants in both groups will attend the clinic regularly to assess the any remyelination that has occurred.
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
Addenbrookes Hospital (UK)
When is the study starting and how long is it expected to run for?
October 2015 to March 2016
Who is funding the study?
Multiple Sclerosis Society (UK)
Who is the main contact?
Mrs Arti Gulati
Trial website
Additional identifiers
EudraCT number
2014-003145-99
ClinicalTrials.gov number
Protocol/serial number
19281
Study information
Scientific title
A randomised placebo-controlled study of the safety and tolerability of a retinoid-X receptor agonist's ability to promote remyelination in people with relapsing-remitting multiple sclerosis already on interferon-beta therapy: a phase 2a trial
Acronym
Study hypothesis
The aim of this study is to establish the safety and tolerability of bexarotene in the treatment of relapsing remitting multiple sclerosis.
Ethics approval
Westminster Research Ethics Committee, 19/03/2015, ref: 15/LO/0108
Study design
Randomised placebo-controlled phase 2a trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Topic: Neurological disorders; Subtopic: Neurological (all Subtopics); Disease: Multiple Sclerosis
Intervention
Participants are randomly allocated into two groups who receive a different medication for a period of nine months. Those in the first group are given Bexarotene and those in the second group are given a placebo. During the nine month study period, participants in both groups will have regular assessments.
Intervention type
Drug
Phase
Phase II
Drug names
Bexarotene
Primary outcome measures
Number of adverse events and withdrawals attributable to bexarotene are determined at 9 months.
Secondary outcome measures
Change in mean lesional MTR between month 0 and month 6 for lesions selected for each patient.
Overall trial start date
01/10/2015
Overall trial end date
31/03/2016
Reason abandoned
Eligibility
Participant inclusion criteria
1. Aged between 30 and 50 years inclusive
2. Able to provide informed consent
3. Relapsing remitting multiple sclerosis as per the McDonald 2010 criteria, including an MRI satisfying the radiological criteria
4. At least five T2 lesions, attributable to MS, on baseline MRI brain scan
5. Kurtzke Expanded Disability Status Scale (EDSS) 3.0-6.0
6. At least one relapse in the two years prior to screening
7. At the time of screening (and for at least the last 6 months) being treated with interferon-beta (any preparation)
8. Able and willing to comply with all study requirements
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 50; UK Sample Size: 50; Description: A total of 50 patients will be enrolled in the study. 25 will receive the drug (bexarotene) and the other 25 will receive a matched placebo
Participant exclusion criteria
1. Pregnant, lactating or planning pregnancy during course of trial
2. Female and male participants unwilling or unable to use two reliable non-hormonal methods of contraception during the course of the trial and for one month thereafter
3. Taking gemfibrozil
4. Taking disease-modifying therapy for multiple sclerosis, other than interferon-beta within the previous six months
5. Significant renal or hepatic impairment (Grade III or worse)
6. Known hypersensitivity to bexarotene or to any of the excipients of the product
7. Unwillingness to take a product containing gelatin
8. Known reaction to gadolinium (within the contrast agent used for MRI scans)
9. History of pancreatitis
10. Fasting triglycerides over 2.3 mmol/L or baseline dyslipidaemia requiring treatment
11. Known hypervitaminosis A
12. Uncontrolled thyroid disease
13. Excessive alcohol consumption (>24units/week for men, >14 units/week for women)
14. Uncontrolled diabetes mellitus
15. Biliary tract disease
16. Hereditary fructose intolerance
17. Use of CYP3A4-substrates (ketoconazole, itraconazole, protease inhibitors, clarithromycin and erythromycin) or CYP3A4-inducers (rifampicin, phenytoin, dexamethasone or phenobarbital), unless patients are willing to stop these (and it is safe to do so)
18. Any other significant disease, disability or investigation result which in the opinion of the Investigator may either put the participant at risk because of participation in the study, or may influence the result of the study, or the participant’s ability to participate in the study
Recruitment start date
01/10/2015
Recruitment end date
31/03/2016
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Funders
Funder type
Charity
Funder name
Multiple Sclerosis Society
Alternative name(s)
MS Society
Funding Body Type
private sector organisation
Funding Body Subtype
professional associations and societies
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary