Interventional Study to Evaluate the Clinical Effects and Safety of the Nutraceutical Compound BrainUp-10® in a Cohort of Patients with Alzheimer’s Disease: A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Trial

Article type: Research Article

Authors: Guzman-Martinez, Leonardo^a | Farías, Gonzalo A.^{b; c} | Tapia, José P.^a | Sánchez, María P.^d | Fuentes, Patricio^{b; c} | Gloger, Sergio^e | Maccioni, Ricardo B.^{a; b; c; *}

Affiliations: [a] Laboratory of Neuroscience and Functional Medicine, Faculty of Sciences, International Center for Biomedicine (ICC), University of Chile, Santiago, Chile | [b] Department of Neurology, Faculty of Medicine, University of Chile, Santiago, Chile | [c] Center for Advanced Clinical Investigation (CICA), Faculty of Medicine, University of Chile, Santiago, Chile | [d] Faculty of Chemistry and Biology, University of Santiago of Chile, Santiago, Chile | [e] Biomedica Research Group, Santiago, Chile

Correspondence: [*] Correspondence to: Ricardo B. Maccioni, MD, PhD, International Center for Biomedicine, Avda. Vitacura 3568, D511-512, Vitacura, Santiago, Chile. E-mail: [email protected].

Abstract: Background:Clinically-evaluated nutraceuticals are candidates for Alzheimer’s disease (AD) prevention and treatment. Phase I studies showed biological safety of the nutraceutical BrainUp-10®, while a pilot trial demonstrated efficacy for treatment. Cell studies demonstrated neuroprotection. BrainUp-10® blocks tau self-assembly. Apathy is the most common of behavioral alterations. Objective:The aim was to explore efficacy of BrainUp-10® in mitigating cognitive and behavioral symptoms and in providing life quality, in a cohort of Chilean patients with mild to moderate AD. Methods:The was a multicenter, randomized, double blind, placebo-controlled phase II clinical study in mild to moderate AD patients treated with BrainUp-10® daily, while controls received a placebo. Primary endpoint was Apathy (AES scale), while secondary endpoints included Mini-Mental State Examination (MMSE), Trail Making Test (TMT A and TMT B), and Neuropsychiatry Index (NPI). AD blood biomarkers were analyzed. Laboratory tests were applied to all subjects. Results:82 patients were enrolled. The MMSE score improved significantly at week 24 compared to baseline with tendency to increase, which met the pre-defined superiority criteria. NPI scores improved, the same for caregiver distress at 12th week (p = 0.0557), and the alimentary response (p = 0.0333). Apathy tests showed a statistically significant decrease in group treated with BrainUp-10®, with p = 0.0321 at week 4 and p = 0.0480 at week 12 treatment. A marked decrease in homocysteine was shown with BrainUp-10® (p = 0.0222). Conclusion:Data show that BrainUp-10® produces a statistically significant improvement in apathy, ameliorating neuropsychiatric distress of patients. There were no compound-related adverse events. BrainUp-10® technology may enable patients to receive the benefits for their cognitive and behavioral problems.

Keywords: Alzheimer’s disease, blood biomarkers, BrainUp-10®, clinical trial, nutraceutical compound

DOI: 10.3233/JAD-201501

Journal: Journal of Alzheimer's Disease, vol. 81, no. 3, pp. 1231-1241, 2021