1. In comparison to placebo, ENT-01 increased rates of complete spontaneous bowel movements per week for patients with Parkinson’s disease (PD).
2. No serious adverse events occurred with the use of ENT-01 and the most commonly reported adverse effect was nausea.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Non-motor symptoms of PD can significantly impair a patient’s quality of life and increase the overall symptom burden of PD. Constipation is a common symptom challenge of PD which can be distressing, difficult to manage, and refractory to standard therapy. A proposed mechanism of how PD causes constipation is the build-up of aggregates of alpha-synuclein in the gastrointestinal tract. ENT-01 is a novel compound that acts to target alpha-synuclein to prevent aggregation which leads to constipation. This study was a randomized controlled trial comparing the safety and efficacy of ENT-01 in reducing constipation and neuropsychiatric symptoms associated with PD against a placebo. Results found that ENT-01 did cause a significant reduction in constipation rates when compared to the placebo control. It was not associated with significant adverse events, and it is unclear whether it caused a significant reduction in neuropsychiatric symptoms. Although this study demonstrated the superiority of ENT-01 over a placebo in constipation symptoms, future investigations comparing ENT-01 with standard therapies for constipation in PD are required to elicit its therapeutic potential.
In-Depth [randomized controlled trial]: This study was a double-blind, randomized controlled trial evaluating the safety and efficacy of ENT-01 in managing neuropsychiatric symptoms and constipation for patients with PD against a placebo control. Adults with diagnosed PD and constipation without an alternate identifiable cause between the ages of 18 to 90 were included. A total of 150 patients were randomly assigned to receive oral ENT-01 or placebo pills in a 3:1 ratio. The primary outcomes of interest were safety and efficacy. Safety was measured in terms of absolute reporting of adverse effects, such as vomiting, diarrhea, and abdominal pain. Efficacy was measured in terms of the number of complete spontaneous bowel movements (CSBMs), as well as the effect on neuropsychiatric symptoms as measured on standardized testing tools. Results of the primary safety analysis found that ENT-01 was not associated with any drug-related serious adverse events. ENT-01 caused more nausea (p<0.001) and diarrhea (p=0.016) than placebo. Both effects reversed spontaneously or with dose reduction. In terms of the primary efficacy endpoint, ENT-01 increased CSBM rates during the initial fixed-dose period (rate ratio 2.78; 95% Confidence Interval, 1.61-4.81; p<0.001). Once dosing was discontinued, there was no difference in CSBM rates between ENT-01 and placebo (p=0.084). It’s unclear whether ENT-01 had a significant effect on reducing positive symptoms associated with PD, and whether this was significantly different from placebo. However, participants in ENT-01 group had a significantly different MMSE score than the placebo six weeks after the end of treatment (p=0.03), and no worsening of motor function. Overall, this study provided evidence that ENT-01 may be helpful in reducing symptoms of constipation amongst patients with PD in comparison to the placebo.
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