Skip to content

Research at St Andrews

Effect of dronabinol on progression in progressive multiple sclerosis (CUPID): a randomised, placebo-controlled trial

Research output: Contribution to journalArticle

Author(s)

John Zajicek, Susan Ball, David Wright, Jane Vickery, Andrew Nunn, David Miller, Mayam Gomez Cano, David McManus, Sharukh Mallik, Jeremy Hobart, CUPID investigator group

School/Research organisations

Abstract

BACKGROUND: Laboratory evidence has shown that cannabinoids might have a neuroprotective action. We investigated whether oral dronabinol (Δ(9)-tetrahydrocannabinol) might slow the course of progressive multiple sclerosis.

METHODS: In this multicentre, parallel, randomised, double-blind, placebo-controlled study, we recruited patients aged 18-65 years with primary or secondary progressive multiple sclerosis from 27 UK neurology or rehabilitation departments. Patients were randomly assigned (2:1) to receive dronabinol or placebo for 36 months; randomisation was by stochastic minimisation, using a computer-generated randomisation sequence, balanced according to expanded disability status scale (EDSS) score, centre, and disease type. Maximum dose was 28 mg per day, titrated against bodyweight and adverse effects. Primary outcomes were EDSS score progression (masked assessor, time to progression of ≥1 point from a baseline score of 4·0-5·0 or ≥0·5 points from a baseline score of ≥5·5, confirmed after 6 months) and change from baseline in the physical impact subscale of the 29-item multiple sclerosis impact scale (MSIS-29-PHYS). All patients who received at least one dose of study drug were included in the intention-to-treat analyses. This trial is registered as an International Standard Randomised Controlled Trial (ISRCTN 62942668).

FINDINGS: Of the 498 patients randomly assigned to a treatment group, 329 received at least one dose of dronabinol and 164 received at least one dose of placebo (five did not receive the allocated intervention). 145 patients in the dronabinol group had EDSS score progression (0·24 first progression events per patient-year; crude rate) compared with 73 in the placebo group (0·23 first progression events per patient-year; crude rate); HR for prespecified primary analysis was 0·92 (95% CI 0·68-1·23; p=0·57). Mean yearly change in MSIS-29-PHYS score was 0·62 points (SD 3·29) in the dronabinol group versus 1·03 points (3·74) in the placebo group. Primary analysis with a multilevel model gave an estimated between-group difference (dronabinol-placebo) of -0·9 points (95% CI -2·0 to 0·2). We noted no serious safety concerns (114 [35%] patients in the dronabinol group had at least one serious adverse event, compared with 46 [28%] in the placebo group).

INTERPRETATION: Our results show that dronabinol has no overall effect on the progression of multiple sclerosis in the progressive phase. The findings have implications for the design of future studies of progressive multiple sclerosis, because lower than expected progression rates might have affected our ability to detect clinical change.

FUNDING: UK Medical Research Council, National Institute for Health Research Efficacy and Mechanism Evaluation programme, Multiple Sclerosis Society, and Multiple Sclerosis Trust.

Close

Details

Original languageEnglish
Pages (from-to)857-65
Number of pages9
JournalLancet Neurology
Volume12
Issue number9
DOIs
Publication statusPublished - Sep 2013

    Research areas

  • Adult, Cannabinoid Receptor Agonists, Disease Progression, Double-Blind Method, Dronabinol, Female, Humans, Male, Middle Aged, Multiple Sclerosis, Chronic Progressive, Treatment Outcome

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Assessment of a home-based standing frame programme in people with progressive multiple sclerosis (SUMS): a pragmatic, multi-centre, randomised, controlled trial and cost-effectiveness analysis

    Freeman, J. A., Hendrie, W., Jarrett, L., Hawton, A., Barton, A., Dennett, R., Jones, B., Zajicek, J. P. & Creanor, S., 1 Aug 2019, In : Lancet Neurology. 18, 8, p. 736-747

    Research output: Contribution to journalArticle

  2. Machine-learning based identification of undiagnosed dementia in primary care: a feasibility study

    Jammeh, E. A., Carroll, C. B., Pearson, S. W., Escudero, J., Anastasiou, A., Zhao, P., Chenore, T., Zajicek, J. & Ifeachor, E., 12 Jun 2018, In : BJGP Open. 2, 2, 13 p., bjgpopen18X101589.

    Research output: Contribution to journalArticle

  3. Improving the quality of cognitive screening assessments: ACEmobile, an iPad-based version of the Addenbrooke's Cognitive Examination-III

    Newman, C. G. J., Bevins, A. D., Zajicek, J. P., Hodges, J. R., Vuillermoz, E., Dickenson, J. M., Kelly, D. S., Brown, S. & Noad, R. F., 2018, In : Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. 10, p. 182-187 6 p.

    Research output: Contribution to journalArticle

  4. Balance Right in Multiple Sclerosis (BRiMS): a guided self-management programme to reduce falls and improve quality of life, balance and mobility in people with secondary progressive multiple sclerosis: a protocol for a feasibility randomised controlled trial

    Gunn, H., Andrade, J., Paul, L., Miller, L., Creanor, S., Green, C., Marsden, J., Ewings, P., Berrow, M., Vickery, J., Barton, A., Marshall, B., Zajicek, J. & Freeman, J. A., 27 Jul 2017, In : Pilot and Feasibility Studies. 4, 12 p., 26.

    Research output: Contribution to journalArticle

  5. Time-and region-specific season of birth effects in multiple sclerosis in the United Kingdom

    Cruz, P. M. R., Matthews, L., Boggild, M., Cavey, A., Constantinescu, C. S., Evangelou, N., Giovannoni, G., Gray, O., Hawkins, S., Nicholas, R., Oppenheimer, M., Robertson, N., Zajicek, J., Rothwell, P. M. & Palace, J., 1 Aug 2016, In : JAMA Neurology. 73, 8, p. 954-960 7 p.

    Research output: Contribution to journalArticle

Related by journal

  1. Assessment of a home-based standing frame programme in people with progressive multiple sclerosis (SUMS): a pragmatic, multi-centre, randomised, controlled trial and cost-effectiveness analysis

    Freeman, J. A., Hendrie, W., Jarrett, L., Hawton, A., Barton, A., Dennett, R., Jones, B., Zajicek, J. P. & Creanor, S., 1 Aug 2019, In : Lancet Neurology. 18, 8, p. 736-747

    Research output: Contribution to journalArticle

  2. Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECTION): A multicentre, randomised, double-blind extension trial

    Giovannoni, G., Gold, R., Selmaj, K., Havrdova, E., Montalban, X., Radue, E. W., Stefoski, D., McNeill, M., Amaravadi, L., Sweetser, M., Elkins, J. & O'Neill, G., 2014, In : Lancet Neurology. 13, 5, p. 472-481 10 p.

    Research output: Contribution to journalArticle

  3. Lithium in patients with amyotrophic lateral sclerosis (LiCALS): a phase 3 multicentre, randomised, double-blind, placebo-controlled trial

    Group, UKMND-LALS. S., Apr 2013, In : Lancet Neurology. 12, 4, p. 339-345 7 p.

    Research output: Contribution to journalArticle

  4. Rating scales as outcome measures for clinical trials in neurology: problems, solutions, and recommendations

    Hobart, J. C., Cano, S. J., Zajicek, J. P. & Thompson, A. J., Dec 2007, In : Lancet Neurology. 6, 12, p. 1094-105 12 p.

    Research output: Contribution to journalArticle

ID: 242547407

Top