Nicotinamide Supplementation Improves Physical Performance in Older Adults at Risk of Falls
NCT Number: NCT06465602
Acronym: NICE-FIT
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Frailty|Fall|Frailty Syndrome|Falls
Interventions: DRUG: Nicotinamide|DRUG: Placebo
Sponsor: University of Chile
Collaborators: Centro FONDAP de Gerociencia, Salud mental y Metabolismo (GERO)|Center for Advanced Clinical Research (CICA ) - University of Chile
Sex: ALL
Age: OLDER_ADULT
Enrollment: 60
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: TRIPLE (PARTICIPANT, CARE_PROVIDER, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-05-21
Completion Date: 2025-02-28
Locations: Hospital Clínico Universidad de Chile, Santiago, Chile

Summary:
Falls are unplanned events resulting in contact with a lower surface. They are common in older adults, affecting one in three individuals over 65 years old. They have serious consequences, ranging from physical injuries (fractures, traumatic brain injury) to psychological repercussions. Physical training focused on muscle strength, balance, and gait has consistently been shown to prevent falls. However, there are significant challenges in its implementation, such as the need for trained personnel and long intervention times, which are associated with high costs. Therefore, developing strategies to improve the efficiency of physical training programs in older adults is mandatory. The reduced response to physical training in older adults compared to younger individuals is a well-documented phenomenon, reflecting physiological changes associated with aging.

Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme for cells, mediating energy metabolism and participating in crucial processes such as DNA repair, mitochondrial function, and cell death. As we age, NAD+ levels decrease in various tissues (including the brain and muscle), contributing to the development of aging phenotypes and associated pathologies. Preclinical evidence suggests that increasing NAD+ levels reduces the appearance of aging phenotypes. During physical activity, cellular metabolic pathways that increase the demand for NAD+ to support energy production in mitochondria are activated. This increase in demand is associated with the upregulation of key enzymes involved in NAD+ degradation promoted by exercise. Considering the decrease in cellular levels of this coenzyme associated with aging, it can be hypothesized that NAD+ deficiency may play a significant role in the reduced response of older adults to training programs. Nicotinamide, a water-soluble form of vitamin B3 currently considered a nutritional supplement, is a fundamental precursor for NAD+ synthesis, capable of raising cellular levels of it. It has already been used in clinical practice in the treatment of certain endocrinological and dermatological conditions. This study aims to determine through a randomized clinical trial whether nicotinamide supplementation improves physical performance in older adults at risk of falls undergoing a physical training program.

Primary Outcome Measures: Improvement in physical performance, Assess the change in total Short Physical Performance Battery (SPPB) performance from baseline to post-4 weeks, Four weeks
Secondary Outcome Measures: Posturography, Change Center of pressure (COP) between baseline and post-training in posturography, Four weeks|Dynamometry, Change in dynamometry performance between baseline and post-training, Four weeks|Quadriceps saturation, Change in quadriceps saturation after a 5-squat test, Four weeks|Adherence to medication, Nicotinamide/placebo usage via self-report survey, Four weeks|Adverse effects, Assessment of adverse effects using a standardized evaluation guideline., Four weeks|Plasma sample analysis, Nicotinamide leves, Interleukin-13 (IL-13), Interleukin-1(IL-1), Interleukin-6 (IL-6), mixed lineage kinase domain-like (MLKL), receptor interacting protein kinase 3 (RIPK3) and chemokine C-C ligand 2 (CCL-2), Four weeks