Condition category
Nervous System Diseases
Date applied
14/10/2015
Date assigned
14/10/2015
Last edited
14/10/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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

Contact information

Type

Public

Primary contact

Mrs Arti Gulati

ORCID ID

Contact details

Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

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

Sponsor information

Organisation

Cambridge University Hospitals NHS Foundation trust & University of Cambridge (Comprehensive)

Sponsor details

Research Services Department
Box 277
Addenbrooke’s Hospital
Hill Road
Cambridge
CB2 2QQ
United Kingdom

Sponsor type

Hospital/treatment centre

Website

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

Publication citations

Additional files

Editorial Notes