Striking a Nerve: Allergy Drug Tested for MS

Published: Feb 6, 2014

By John Gever, Deputy Managing Editor, MedPage Today

Last fall, I wrote in this space about a planned trial of an over-the-counter drug that potentially "could stave off disability in multiple sclerosis patients." The post drew a lot of heat from readers because I didn't name the drug or the researcher leading the effort, at his request.

Now he and his colleagues have gone public, at least a little. Details of the trial have beenpublished at Clinicaltrials.gov, so the cat is officially out of the bag.

Here's the skinny: the drug is clemastine, the active ingredient in the OTC allergy drug Tavist.Ari Green, MD, of the University of California San Francisco is the principal investigator (although he is not the researcher who spilled the beans at last fall's American Neurological Association meeting; that was his UCSF colleague, Jonah Chan, PhD).

As I wrote earlier, the drug was found in a novel high-throughput screening program aimed at identifying compounds that would promote oligodendrocyte-driven myelinating activity. It is the deficiency in this activity in MS that is thought to leave nerve fibers stripped of their myelin sheaths, leading to axonal damage, loss of nerve function, and ultimately clinical disability.

Patients with relapsing-remitting MS and with minimal to moderate disability (EDSS scores of 0 to 6) are now being recruited for the study, with an enrollment target of 50. The randomized trial has a cross-over design, with patients receiving either placebo or clemastine pills for 3 months and then the other for 2 months.

The primary outcome measures include fatigue, myelin water volume and magnetization transfer ratios, and EDSS score progression. Safety biomarkers dominate the secondary outcomes.

Results are expected by September of this year.

The design raised some questions for me. With two of the three primary endpoints being clinical -- fatigue and physical disability -- the 5-month trial duration and the inclusion of patients with minimal baseline disability seems, at least superficially, likely to make it hard to detect an effect if there is one.

It's noteworthy that fatigue is a safety endpoint as well as potentially an efficacy outcome -- in patients with allergies, the drug causes fatigue.

Also, focusing on patients with relapsing-remitting MS rather than those with primary or secondary progressive MS seems unnecessarily restrictive. I would have thought a remyelinating agent's effects would be at least as easily detected in the latter, if not more.

When I spoke to Chan following his ANA presentation in October, one of his reasons for asking me to withhold details was that this trial could be the only shot at testing whether clemastine does have remyelinating effects in live humans. A negative result would almost certainly mean no funding for a second attempt. So these trial design choices that seem to weigh against finding an effect are a little perplexing.

But I'm no expert in this area, just a semi-educated layperson. I hope to get answers from Green and Chan, which I will relay in this space.

By the way, if you're an MS patient, or a clinician thinking about suggesting clemastine to patients, know this: other than the high-throughput screen result in a cell culture assay, there is not one iota of evidence that the drug has any benefit in MS. No epidemiological studies, no case reports, no animal research, nada.

And if clemastine doesn't promote remyelination, it will likely worsen fatigue, perhaps the most common clinical complaint in MS. On the basis of current evidence, the benefit-risk balance clearly tips toward risk.

Striking a Nerve is a blog by John Gever for readers interested in neurology and psychiatry.