Randomized, double-blind, placebo-controlled trial of ISC 17536, an oral inhibitor of transient receptor potential ankyrin 1, in patients with painful diabetic peripheral neuropathy: impact of preserved small nerve fiber function
| Autor: | Robert Holland, Yacine Salhi, Neelufar Mozaffarian, Sunil M. Jain, Ralf Baron, Ramanathan Balamurugan, Monika Tandon, Roy Freeman, Girish Gudi |
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| Rok vydání: | 2021 |
| Předmět: |
Ankyrins
medicine.medical_specialty Placebo-controlled study Pain Nerve Fibers Diabetic Neuropathies Double-Blind Method Internal medicine Diabetes mellitus Diabetes Mellitus medicine Clinical endpoint Humans business.industry Chronic pain Peripheral Nervous System Diseases medicine.disease Treatment Outcome Anesthesiology and Pain Medicine Peripheral neuropathy Nociception Neurology Neuropathic pain Quality of Life Nociceptor Neuralgia Neurology (clinical) Chronic Pain business |
| Zdroj: | Pain. 163:e738-e747 |
| ISSN: | 1872-6623 0304-3959 |
| DOI: | 10.1097/j.pain.0000000000002470 |
| Popis: | Patients with chronic pain syndromes, such as those with painful peripheral neuropathy due to diabetes mellitus, have limited treatment options and suffer ongoing attrition of their quality of life. Safer and more effective treatment options are needed. One therapeutic approach encompasses phenotypic characterization of the neuropathic pain subtype, combined with the selection of agents that act on relevant mechanisms. ISC 17536 is a novel, orally available inhibitor of the widely expressed pain receptor, transient receptor potential ankyrin 1, which mediates nociceptive signaling in peripheral small nerve fibers. In this randomized, placebo-controlled, proof-of-concept trial, we assessed the safety and efficacy of 28-day administration of ISC 17536 in 138 patients with chronic, painful diabetic peripheral neuropathy and used quantitative sensory testing to characterize the baseline phenotype of patients. The primary end point was the change from baseline to end of treatment in the mean 24-hour average pain intensity score based on an 11-point pain intensity numeric rating scale. The study did not meet the primary end point in the overall patient population. However, statistically significant and clinically meaningful improvement in pain were seen with ISC 17536 in an exploratory hypothesis-generating subpopulation of patients with preserved small nerve fiber function defined by quantitative sensory testing. These results may provide a mechanistic basis for targeted therapy in specific pain phenotypes in line with current approaches of "precision medicine" or personalized pain therapeutics. The hypothesis is planned to be tested in a larger phase 2 study. |
| Databáze: | OpenAIRE |
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