A trial to determine bexarotene's safety and tolerability and its ability to promote brain repair in patients with multiple sclerosis
| ISRCTN | ISRCTN14265371 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14265371 |
| EudraCT/CTIS number | 2014-003145-99 |
| Secondary identifying numbers | CPMS 19281 |
- Submission date
- 14/10/2015
- Registration date
- 14/10/2015
- Last edited
- 07/11/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English summary of protocol
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 November 2019
Who is funding the study?
Multiple Sclerosis Society (UK)
Who is the main contact?
Mrs Arti Gulati
Contact information
Public
Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Study information
| Study design | Randomized placebo-controlled phase 2a trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| 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 |
| Study objectives | The aim of this study is to establish the safety and tolerability of bexarotene in the treatment of relapsing remitting multiple sclerosis. |
| Ethics approval(s) | Westminster Research Ethics Committee, 19/03/2015, ref: 15/LO/0108 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Bexarotene |
| Primary outcome measure | 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 study start date | 01/10/2015 |
| Completion date | 15/11/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 30 Years |
| Upper age limit | 50 Years |
| Sex | 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 |
| Total final enrolment | 52 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 17/01/2017 |
| Date of final enrolment | 17/05/2019 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Cambridge
CB2 0QQ
United Kingdom
Sponsor information
Hospital/treatment centre
Research Services Department
Box 277
Addenbrooke’s Hospital
Hill Road
Cambridge
CB2 2QQ
England
United Kingdom
"ROR" |
https://ror.org/04v54gj93 |
|---|
Funders
Funder type
Charity
Private sector organisation / Associations and societies (private and public)
- Alternative name(s)
- Multiple Sclerosis Society of Great Britain and Northern Ireland, The MS Society, MS Society UK, Multiple Sclerosis Society UK, MS Society
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 23/08/2021 | 23/08/2021 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Other publications | 19/05/2022 | 07/11/2023 | Yes | No | |
| Results article | 17/09/2022 | 07/11/2023 | Yes | No |
Editorial Notes
07/11/2023: Publication references added.
06/05/2022: The following changes were made to the trial record:
1. The recruitment start date was changed from 01/10/2015 to 17/01/2017.
2. The recruitment end date was changed from 31/03/2016 to 17/05/2019.
3. The overall end date was changed from 31/03/2016 to 15/11/2019.
4. The plain English summary was updated to reflect these changes.
23/08/2021: Publication reference and total final enrolment number added.
31/05/2018: No publications found, verifying study status with principal investigator.
