Results from a Widely-Inclusive, Historically-Controlled, Virtual Pilot Trial of Theracurmin

Background: Curcumin is a polyphenol naturally found in turmericand curry powder. It could theoretically slow ALS progression viaeffects on neuroinflammation, oxidative stress, protein aggregationand the gut microbiome. In a cell model of ALS, curcumin treatmentreduced hyperexcitability, markers of oxidative stress & protein aggre-gation, and improved mitochondrial function. In two small flawedhuman trials, curcumin treatment was associated with improved ALSoutcomes. Nine "ALS Reversals" are associated with forms of curcu-min. When taken orally, curcumin is safe and well-tolerated.Hypothesis: A water-soluble form of curcumin called Theracurmin willbe safe, tolerable, slow ALS progression and change the gutmicrobiome. Methods: We conducted a single-center trial in which 50 people withALS were treated with Theracurmin from Integrative Therapeutics ata dose of 1 capsule twice daily for 6 months. Outcomes includedsafety, tolerability, monthly ALSFRS-R scores, patient-reported effi-cacy and burden scores, and 16s gut microbiome sequencing. Likeother ROAR Trials (https://alsreversals.com/r-o-a-r-program/), thisone was widely inclusive, entirely virtual, utilized historical rather thanplacebo controls and had results available in real time on the Patient-sLikeMe website. Results to date: We enrolled 50 patients in 12 months (enroll-ment rate 4.2 patients per site per month). Participants were pri-marily white (n=43) males (n=31), with a mean age of 61 years.Thirty-eight participants were on Riluzole, one was also on Edara-vone. Participants' disease duration was longer than most trials,including some with ALS for 10 years. There were no seriousadverse events related to Theracurmin. Twenty-one participantshad non-serious adverse events, most commonly gastrointestinalin nature (loose stools/diarrhea). Thirty-five patients (70%) com-pleted the 6-month study. The most common reason for early ter-mination was disease progression. Efficacy and microbiomeanalyses are underway. Discussion/Conclusions: Theracurmin treatment appeared safe andwell-tolerated. Efficacy and microbiome analyses are underway; thesewill be presented at the NEALS meeting. This unusual trial design wasagain able to enroll more quickly and include a more diverse popula-tion than most ALS trials; it retained participants equally well. It couldserve as a model for larger “de-centralized” trials or expanded accessprograms using products that appear reasonably safe.

Duke Scholars

Author Xiaoyan Li Neurology, Neuromuscular Disease