Probiotic Supplements For Depression In Parkinson’s Disease (Pro-Park): A Randomized, Triple-Blind, Placebo-Controlled, Phase IIb Trial Protocol
Authors:   PPCR Program, Executive and Continuing Education, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Schulte Farina Giovani , Nirta Lauren ,   PPCR Program, Executive and Continuing Education, Harvard T.H. Chan School of Public Health, Boston, MA, USA,   MediSpeak Communications, Busan, South Korea, Lima de Oliveira Lilia Maria ,   PPCR Program, Executive and Continuing Education, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Chamba Rospiglioni Jose Luis ,   PPCR Program, Executive and Continuing Education, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Pimentel Vespasiano Celso Francisco ,   PPCR Program, Executive and Continuing Education, Harvard T.H. Chan School of Public Health, Boston, MA, USA,   Adium SA, São Paulo, SP, Brazil, Link Woite Naira ,   PPCR Program, Executive and Continuing Education, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Radi Zahran Ibrahim Antonio ,   PPCR Program, Executive and Continuing Education, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Checo Mariana ,   PPCR Program, Executive and Continuing Education, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Parron Fernandes Kevin Baros ,   PPCR Program, Executive and Continuing Education, Harvard T.H. Chan School of Public Health, Boston, MA, USA,   School of Medicine, Pontifical Catholic University of Paraná (PUCPR), Londrina, PR, Brazil,   Département des Sciences de la Santé, Centre Intersectoriel en Santé Durable, Laboratoire de recherche BioNR, Université du Québec à Chicoutimi (UQAC), Saguenay, Québec, Canada, Blinov Dmitrii ,   PPCR Program, Executive and Continuing Education, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Caruso Rosario ,   PPCR Program, Executive and Continuing Education, Harvard T.H. Chan School of Public Health, Boston, MA, USA,   Clinical Research Service, IRCCS Policlinico San Donato, San Donato Milanese, Italy,   Department of Biomedical Sciences for Health, University of Milan, Milan, Italy, Mercado Dominguez Aimee Michelle ,   PPCR Program, Executive and Continuing Education, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Zamalloa Masias Natalia Lorena ,   PPCR Program, Executive and Continuing Education, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Meza-Venegas Joyce ,   PPCR Program, Executive and Continuing Education, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Saeed Ibrahim Mohamed Ibrahim ,   PPCR Program, Executive and Continuing Education, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Nishizawa Takuro ,   PPCR Program, Executive and Continuing Education, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Jaldin Pinto Angelica Valeria ,   PPCR Program, Executive and Continuing Education, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Urja Prakrity ,   PPCR Program, Executive and Continuing Education, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Areán-Sanz Rodrigo ,   PPCR Program, Executive and Continuing Education, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Saretta Schwartz Denise ,   PPCR Program, Executive and Continuing Education, Harvard T.H. Chan School of Public Health, Boston, MA, USA,   Professor Doctor at the School of Veterinary Medicine and Animal Science (FMVZ), University of São Paulo (USP), São Paulo, Brazil, Tamayo Arturo ,   PPCR Program, Executive and Continuing Education, Harvard T.H. Chan School of Public Health, Boston, MA, USA,   Assistant Professor of Neurology and Cerebrovascular Diseases, The Max Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada
Published: August 2024

Introduction: Parkinson’s disease (PD) is the second most prevalent degenerative neurological disorder globally. Comorbid major depressive disorder (MDD) is a common occurrence which adds considerably to disease burden. This protocol presents a study designed to investigate the effect of add-on probiotic supplementation on MDD in patients with PD. Methods: We designed a phase IIb, randomized, triple-blind, placebo-controlled study to evaluate the efficacy and safety of probiotics as an adjuvant treatment to selective serotonin reuptake inhibitors (SSRI) for patients with mild to moderate PD and MDD. Participants will be randomized to probiotics (n=62) or placebo (n=62) arms using a permuted block randomization approach. Co-primary outcomes include changes in Montgomery-Åsberg Depression Rating Scale (MADRS)scores and SSRI equivalent doses, which will be compared between groups using a bivariate joint model. Secondary outcomes will include changes in both Beck Depression Inventory-II (BDI-II) score and levodopa dose, which will be analyzed using t-tests or Mann-Whitney tests as appropriate. Concurrent validity between MADRS and BDI-II will be assessed using Pearson’s or Spearman’s correlation tests. Safety will be evaluated by comparing discontinuation rates and adverse events between groups using chi-square. Data will be analyzed using intention-to-treat and per-protocol analyses, and missing data will be addressed using multiple imputation methods. Discussion: Probiotics represent a potential new approach to managing depression in patients with PD by targeting the gut-brain axis. The results will offer crucial information about the safety and efficacy of a low-cost and readily available supplement that may alleviate depression in this vulnerable population.