They did a screen of many drugs and pulled out one of the best called clemastine. This was shown to stimulate myelin formation and in animal models it helped to speed up the remyelination process.
Clemastine is old type of anti-histamine (anti-itch) that has fallen out of favour, because it induces fatigue and drowsiness. It is used for drying you up when you have a streaming eyes or nose.
So the trial worked.
Green et al. Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD): a randomised, controlled, double-blind, crossover trial.Lancet. 2017. pii: S0140-6736(17)32346-2.
BACKGROUND: Myelin in the CNS is a specialised extension of the oligodendrocyte plasma membrane and clemastine fumarate can stimulate differentiation of oligodendrocyte precursor cells in vitro, in animal models, and in human cells. We aimed to analyse the efficacy and safety of clemastine fumarate as a treatment for patients with multiple sclerosis.
METHODS: We did this single-centre, 150-day, double-blind, randomised, placebo-controlled, crossover trial (ReBUILD) in patients with relapsing multiple sclerosis with chronic demyelinating optic neuropathy on stable immunomodulatory therapy. Patients were randomly to receive either clemastine fumarate (5·36 mg orally twice daily) for 90 days followed by placebo for 60 days (group 1), or placebo for 90 days followed by clemastine fumarate (5·36 mg orally twice daily) for 60 days (group 2). The primary outcome was shortening of P100 latency delay on full-field, pattern-reversal, visual-evoked potentials. The trial is registered with ClinicalTrials.gov, number NCT02040298.
FINDINGS: Between Jan 1, 2014, and April 11, 2015, we randomly assigned 50 patients to group 1 (n=25) or group 2 (n=25). All patients completed the study. The primary efficacy endpoint was met with clemastine fumarate treatment, which reduced the latency delay by 1·7 ms/eye (95% CI 0·5-2·9; p=0·0048) Clemastine fumarate treatment was associated with fatigue, but no serious adverse events were reported.
INTERPRETATION: To our knowledge, this is the first randomised controlled trial to document efficacy of a remyelinating drug for the treatment of chronic demyelinating injury in multiple sclerosis. Our findings suggest that myelin repair can be achieved even following prolonged damage.
It is licensed for use in humans. It costs a few pence, so NICE isn’t going to waste any sleep over this one.
Another trial? Then What?
Because the dose used is massive, compared to what’s usually prescribed. So will a repeat study be needed before it can it be prescribed off-label as the 5.36mg dose used in the trial, is twice that normally used (2.68mg). No wonder the participants got fatigue.
7. (Importantly) are the results clinically meaningful?
Questions, questions questions.
More from the Neuros will be forthcoming…