Abstract Details

Title Orally-administered TRPV1 and TRPA1 activators reduce Night Leg Cramps in a randomized, blinded, placebo-controlled, crossover human trial

Topic Sleep

Presentation(s) (-)

Poster/Presentation
Number 013

Background Nocturnal leg cramps (NLC) affect millions of Americans, and there are no FDA-approved drug therapies. Recent experimental evidence argues that hyperexcitability of alpha-motor neurons is central to generating muscle cramps. Initial observations in athletes led to the hypothesis that activation of TRPV1/TRPA1 ion channels in mucous membranes of the oropharynx/upper GI tract increase inhibitory tone in the spinal cord, dampening motor neuron hyperexcitability. Recent evidence in electrically- and voluntarily-induced cramps in athletes supports this hypothesis.

Objective

Design/Methods After an initial placebo run-in period, 50 evaluable subjects (50-77 years) were randomized to either control or study product for two weeks, then crossed over for two weeks.

Results Statistically significant effects were demonstrated on key endpoints: cramp frequency (p<0.05); cramp-free days (p<0.01), the physician-rated Clinical Global Impression of Change (p<0.01); specific sleep disturbance (p<0.05) and pain measures (p<0.05). The product appeared to be safe, well-tolerated with no serious adverse events. The magnitude of cramp reduction appears to be similar to published “Class 1 level” quinine efficacy studies (quinine was banned by the FDA for leg cramps due to safety issues). Finally, a subset of subjects had a pronounced clinical benefit.

Conclusions These results demonstrate that TRP activation can reduce NLC. This supports the novel concept of Chemical Neuro Stimulation, a process whereby small molecules activate TRP ion channels topically, leading to sensory stimulation that in turn reduces hyperexcitability in motor neurons at multiple levels in the spinal cord. The human efficacy signals generated in this study hold promise for a new approach in NLC and cramps in neurological disorders. Based upon these results, we plan to initiate studies with a single molecule TRP activator in NLC, MS and ALS.

Authors/Disclosures
Jennifer M. Cermak, PhD (Flex Pharma)	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file

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