{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T02:32:19Z","timestamp":1784255539646,"version":"3.55.0"},"reference-count":47,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>Muscle cramps are a common symptom in amyotrophic lateral sclerosis (ALS). Ameliorating muscle cramps may improve quality of life in devastating diseases like ALS. A traditional Japanese medicine (Kampo, TJ\u201068) is widely prescribed in Japan for muscle cramps. However, it is not available in the USA. This study evaluated the safety, tolerability, and efficacy of TJ\u201068 in ALS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study was a double\u2010blind, randomized, placebo\u2010controlled crossover trial, consisting of four periods, conducted at three centers in the USA. Safety was evaluated using multiple measures. The primary efficacy outcome was the Visual Analog Scale for Muscle Cramps Affecting Overall Daily Activity (item #5 of the Muscle Cramp Scale (MCS)). The secondary outcomes included the remaining items of the MCS and the Clinical Global Impression of Changes (CGIC), among others. The study was planned to enroll 22 participants with ALS within 2\u2009years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The enrollment was slow and was completed with 11 participants. There were no serious safety issues and TJ\u201068 was well tolerated. Although the primary outcome measure did not reach statistical significance (<jats:italic>p<\/jats:italic>\u2009=\u20090.35), several secondary measures showed significant results: MCS #1 triggering of cramps (<jats:italic>p<\/jats:italic>\u2009=\u20090.01), MCS #2 cramp frequency (<jats:italic>p<\/jats:italic>\u2009=\u20090.03), MCS Additional 1 change of motor behaviors (<jats:italic>p<\/jats:italic>\u2009=\u20090.02), and CGIC assessed by the evaluator (<jats:italic>p<\/jats:italic>\u2009=\u20090.009). Other outcome measures did not reach statistical significance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The study revealed that N\u2010of\u20101 trial design can detect changes in a small sample size, and TJ\u201068 appeared to be safe. Larger studies are needed to confirm the efficacy of TJ\u201068.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.28459","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T03:29:40Z","timestamp":1750649380000},"page":"485-492","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Placebo\u2010Controlled, Randomized Double\u2010Blind N\u2010Of\u20101 Trial to Study Safety and Potential Efficacy of <scp>TJ<\/scp>\u201068 for Improving Muscle Cramps in Patients With Amyotrophic Lateral Sclerosis: A Pilot Study"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6259-8923","authenticated-orcid":false,"given":"Hiroshi","family":"Mitsumoto","sequence":"first","affiliation":[{"name":"Department of Neurology Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Mailman School of Public Health, Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1725-9866","authenticated-orcid":false,"given":"Bj\u00f6rn","family":"Oskarsson","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Jacksonville  Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace E.","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Neurology Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard F.","family":"Andrews","sequence":"additional","affiliation":[{"name":"Data Coordinating Center (DCC), Department of Biostatistics Mailman School of Public 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Neurology Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"McElhiney","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Columbia University Irving Medical Center and New York State Psychiatric Institute  New York New York 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