Cannabinoid Use in Progressive Inflammatory brain Disease

Lead Research Organisation: University of Plymouth
Department Name: Sch of Biomedical & Biological Sciences

Abstract

We plan to evaluate whether a cannabis-based medicine (delta 9-THC) has an effect on slowing accumulation of disability in progressive multiple sclerosis (MS) over three years. MS is the commonest cause of disability in young adults and the majority of people affected eventually develop a progressive form of the condition, thought to be due to destruction of nerve cells.
MS treatments can be divided into those aimed at relieving symptoms and those that may alter the course of the condition. Unfortunately, few medicines are effective in MS, and none have been shown to have any effect in the later stages of progressive disease. The recent Cannabinoids in MS (CAMS) study investigated the effects of cannabis–based medicines on muscle stiffness (spasticity) in MS over a fifteen week period, with an option for participants to continue study medication for up to a year. Although the study did not demonstrate any effects on spasticity after fifteen weeks as measured by independent assessors, there was evidence that patients felt that the cannabis medicines helped many symptoms and the study did provide preliminary evidence to suggest that delta 9-THC may reduce accumulation of disability in the longer-term. In addition, new scientific evidence has emerged to suggest that some constituents of cannabis may help nerve cells to survive (neuroprotection). It is therefore possible that this medication may not only help treat symptoms of MS, but may also alter the course of the condition and be neuroprotective.
The CAMS study also highlighted the limitations of measuring the effects of treatments in chronic disease, especially the differences between patient experience and independent assessment e.g. by a doctor. In our new study we will use both old and new ways of assessing the effects of cannabis-based medicines and will continue to develop measurement methods from the patient perspective. This should lead to more effective ways of assessing new treatments in the future.

Technical Summary

Multiple Sclerosis (MS) is the commonest cause of neurological disability in young adults, with a prevalence of around 1 in 800 in most of the UK. Treatments for MS can broadly be divided into symptomatic (such as muscle relaxants and bladder treatments) and so-called disease modifying, most of which are immunomodulatory. The majority of people with MS will ultimately develop more progressive disease, thought to be due to neuronal degeneration. There is now considerable interest in treatments that may be neuroprotective, of which none are available at present.
The recent Cannabinoids in MS (CAMS) study focused on testing symptomatic benefit from cannabinoids over a 15-week period. Participants were included on the basis of having relatively stable MS in the six months prior to study recruitment, and of the 630 who received treatment, 95% had progressive disease. Following the main trial period, patients were offered the opportunity to continue medication in a blinded fashion for up to 12 months, with continuing three-monthly assessments. The primary outcome measure assessed spasticity using the Ashworth scale. No treatment effect was found during the main study, although patients felt that active medication was much more helpful than placebo in alleviating some of their distressing symptoms.
During the course of the study, experimental evidence was emerging to suggest that cannabinoids may have a neuroprotective action. The results of the follow-up study show significant effects on spasticity scores in the tetrahydrocannabinol (delta9-THC) arm, but not the cannabis extract arm. There is also some evidence for an effect on some measures of disability. The proposed study will therefore test whether cannabinoids have a neuroprotective action in progressive MS, building on the success of the CAMS study. In the course of delivering this study we will also continue the important process of developing methodology of clinical trials in chronic disease.
Five hundred patients with progressive MS and EDSS score 4.0-6.5 (walking affected by disease, but still able to walk with aids if necessary) will be randomised to either oral delta9-THC capsules or matched placebo. There will be a 2:1 active: placebo ratio. Recruitment will occur over 18 months, and patients will be followed up for three years on treatment. There will be two primary outcome measures: the physician-based EDSS (overall proportion of patients deteriorating, confirmed at two consecutive six monthly visits), and the patient-based MSIS-29 (overall mean change from baseline to end of study).

Organisations

Publications

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Description MS clinical research network 
Organisation Aberdeen Royal Infirmary
Country United Kingdom 
Sector Hospitals 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation Addenbrooke's Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation Barts Health NHS Trust
Country United Kingdom 
Sector Public 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation Birmingham Community Healthcare NHS Trust
Department West Midlands Rehabilitation Centre
Country United Kingdom 
Sector Hospitals 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation Frenchay Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation Gloucestershire Royal Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation Hertford County Hospital
Department Neurology Department
Country United Kingdom 
Sector Hospitals 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation Imperial College Healthcare NHS Trust
Country United Kingdom 
Sector Hospitals 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation John Radcliffe Hospital
Department Department of Clinical Neurology
Country United Kingdom 
Sector Hospitals 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation Leicester General Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation Musgrove Park Hospital
Department Neurology Department
Country United Kingdom 
Sector Hospitals 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation NHS Ayrshire and Arran
Country United Kingdom 
Sector Public 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation Norfolk and Norwich University Hospital
Department Neurology Department
Country United Kingdom 
Sector Hospitals 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation Poole Hospital NHS Foundation Trust
Department Portland Ward
Country United Kingdom 
Sector Hospitals 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation Queen's Medical Centre
Country United Kingdom 
Sector Hospitals 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation Royal Berkshire NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation Royal Cornwall Hospitals NHS Trust
Country United Kingdom 
Sector Public 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation Royal Hallamshire Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation Royal Preston Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation Royal Victoria Infirmary
Country United Kingdom 
Sector Hospitals 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation Salford Royal NHS Foundation Trust
Department Department of Neurology
Country United Kingdom 
Sector Hospitals 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation University Hospital of North Staffordshire NHS Trust
Country United Kingdom 
Sector Public 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation University Hospital of Wales
Country United Kingdom 
Sector Hospitals 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation University Hospitals Birmingham NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation University Hospitals Coventry and Warwickshire NHS Trust
Country United Kingdom 
Sector Public 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.
 
Description MS clinical research network 
Organisation Western General Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution Designed and obtained funding for multicentre clinical trial.
Collaborator Contribution Recruited participants to clinical trial.
Impact Successful completion of multicentre study.