CUPID is dead. The Cannabis trial

 #MSResearch #MSblog. Cannabis trial bites the dust. Is CUPID dead?

Zajicek J, Ball S, Wright D, Vickery J, Nunn A, Miller D, Cano MG, McManus D, Mallik S, Hobart J; on behalf of the CUPID investigator group. Effect of dronabinol on progression in progressive multiple sclerosis (CUPID): a randomised, placebo-controlled trial. Lancet Neurol. 2013 Jul 12. doi:pii: S1474-4422(13)70159-5

BACKGROUND: Laboratory evidence has shown that cannabinoids might have a neuroprotective action. We investigated whether oral dronabinol (Δ9-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.

After the biggest trial on progressive MSers…after 7 years the drug in cannabis (Tetrahydrocannabinol) fails to show any effect….depressing. They suggest they will learn from the failure. People in the trial irrespective of whether they got the drug did better than expected… and maybe people with less diabability actually reponded to treatment…but will they ever repeat this.

Why would you do this well…….
Fifteen years ago our work in beasties indicates that cannabis may be some use for cannabis control.
Tens years ago the CAMS trial on oral cannabis and THC failed to show any effect,.
Ten years on…. the trial design is developed and the MUSEC trial cannabis now works for symptom control.
Sativex comes to market. Our observations in beasties translates.

Ten years ago or observations in beasties suggest that THC could be useful in the control of progressions and today CUPID is dead. 

A symptom control trial takes a year or two but who is going to spend 5-7 years repeating this?
So probably 10 years of science (my life) flushed down the toilet.

The history of immunosuppressive agents show that intial trials failed until the trial design and biomarkers were developed and now you can find drugs for RRMS within 6 months to 2 years.

 How many drugs will be thrown away in this process..Two down already

CoI: Prof G was part of the trial

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  • As so often, sometimes clinical research is too important to be left to the clinicians! If the cohort of patients had been better selected ie earlier in their progressive phase, I'm sure judging from our animal work this would have shown a positive effect. As it is it joins a lengthening list of promising therapies that disappear down the crapper and in this case further money to do a trial properly is unlikely to be forthcoming.
    Very, very frustrating.

  • Aaron Surin Thursday, July 18, 2013 11:33:00 am wrote

    Oh!! It is very bad but after all they try their best, Tens years ago the CAMS trial on oral cannabis and THC failed to show any effect,. Ten years on…. the trial design is developed and the MUSEC trial cannabis now works for symptom control.

    (Link to massage site removed)If you wish to post in future please remove the link beforehand. Thanks.

  • I'm sorry so much of your time and energy has been flushed down the throne. : ( Speaking only for myself, smoked Canabis relieves my spasms immediately, and lasts for many hours. But then, we are all different. I do await a symptom relief study…

  • There has been a symptom relief study on smoked cannabis…it apparently worked

    However you could get the added benefit of it slowing the processes that drive progression.

    If we look in one of the figures the people with EDSS less than 5.5 showed signficiant benefeit from this treatment

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