The Efficacy of Creatine Supplementation in Improving Cognitive Performance in Adolescents: A Phase-II, Triple-Blind, Randomized Study Protocol
Authors:   Precision Medicine Research, Sidra Medicine, Doha, Ahmed Salma , Bose Gauruv ,   Brigham Multiple Sclerosis Center & Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s Hospital, Boston, MA, USA, 02115, Adenuga Adedire ,   Cedarcrest Hospitals, Abuja, Nigeria, Insfrán Carlos E. ,   Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Ashihara Carolina ,   Hospital Israelita Albert Einstein, São Paulo, Sacoto Daniel ,   Mayo Clinic, Department of Gastroenterology and Hepatology, Rochester, Orbaugh Delaney ,   Universidad Francisco Marroquín, Guatemala City, Ahmed Isra ,   Hamad Medical Corporation, Doha, Vargas Javiera ,   Servicio de Anestesiología, Clínica Alemana de Santiago, Chile, Luiz Gross Jefferson ,   A.C. Camargo Cancer Center. Sao Paulo - Brazil, Alves July ,   Universidade Federal de São Paulo, São Paulo, Moreno Maria ,   Beth Israel Deaconess Medical Center, Boston, Turza Mariana ,   Hospital Provincial Neuquén Dr. Eduardo Castro Rendón. Neuquén, Argentina, Lôbo Matheus ,   A.C. Camargo Cancer Center. Sao Paulo - Brazil, Forian Clerc Olivier ,   Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Cardiac Amyloidosis Program, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, Morejon-Jaramillo Pablo ,   Universidad San Francisco de Quito, Quito, Lora Patricia ,   Pontificia Universidad Católica Madre y Maestra. Santiago, Dominican Republic, Cordeiro Rafael A. ,   Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Niño Rodrigo ,   Clínica Alemana de Santiago, Departamento de Farmacia, Santiago, Gashey Samah N ,   University of almaarefa-KSA-Riyadh, Hayder Ahmed Sara ,   Pharmacy Department, Hamad Medical Corporation (HMC), Doha, Qatar, Salameh Sarah ,   Weill Cornell Medicine-Qatar, Cornell University, Doha., Chemale Yuri ,   Harvard T.H. Chan School of Public Health, Boston, USA, Moreira Thais G. ,   Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115 USA
Published: July 2023

Background/Aims: Creatine supplementation has demonstrated cognitive benefits in neurodegenerative conditions, having a protective effect in the brain's function in stressful situations, with excellent safety (Watanabe et al., 2002). However, any beneficial effects on the cognitive performance of healthy adolescents underperforming in school is unknown. Our objective is to assess whether creatine supplementation improves cognitive performance in 15- to 17-year-old students with an average school grade below the 50th percentile. Methods: This will be a phase-II, triple-blinded, randomized, parallel-group, superiority, single-center trial. Students with grades below the 50th percentile in the prior semester will be enrolled and randomized to receive juice packages containing either creatine monohydrate supplementation (0.1 mg/kg/day), or placebo, for 12 weeks. The primary outcome will be the mean difference in change of Raven’s Standard Progressive Matrices (RSPM) scores from baseline to week 12 between groups. To achieve a 90% power for detecting a 3-point difference in change in the RSPM score, and accounting for drop-out, 116 participants will be included. Secondary outcomes will include the difference in processing speed (SpaceCode), working memory (SpaceMatrix), non-visual memory (backward digit span), percentage change in lean mass, and any safety events. Conclusion: To our knowledge, this will be the most comprehensive study assessing creatine supple-mentation in adolescents. This is a low-risk intervention that has been shown to improve cognitive function in other populations. This study will potentially support the widespread use of creatine supplementation in adolescents with low school performance, while having a positive impact on this population.