Nicotinamide Supplementation Improves Physical Performance in Older Adults at Risk of Falls

Frailty Clinical Trial

— NICE-FIT  

Official title:

Nicotinamide Supplementation Improves Physical Performance in Older Adults at Risk of Falls: a Pilot Randomized Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06465602
• Other study ID #: FONDAP 15150012 GERO
• Status: Recruiting
• Phase: Phase 2
• Start date: May 21, 2024
• Est. completion date: February 28, 2025

Study information

• Verified date: April 2024
• Source: University of Chile
• Contact: Felipe H Salech Morales, MD PhD
• Phone: 229788546
• Email: fhsalech[@]uchile.cl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

To test the hypothesis, a randomized pilot clinical trial will be conducted using block allocation, double-blind (patient and evaluator), designed according to the SPIRIT guidelines for drafting a trial protocol. This study involves the implementation of guided home-based physical training by a physiotherapist (2 sessions per week for 4 weeks) combined with supplementation with nicotinamide (1.5 g/day) or placebo depending on the assigned group. Improvement in physical performance will be evaluated using the Short Physical Performance Battery (SPPB), handgrip strength test, quadriceps dynamometry, posturography, and near-infrared spectroscopy (NIRS) of the quadriceps. The RedCap software will be used for randomization and data analysis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: February 28, 2025
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• Aged 65 years or older
• Living in the community
• Increased risk of falls, defined as:
• More than two falls in the last 12 months or
• Altered balance test (unable to maintain unipedal stance > 5 seconds) or
• SPPB score less than 10 points

Exclusion Criteria:

• Known Muscle Disease (dystrophy, myopathy, or similar)
• Motor sequelae of stroke
• Joint pathology with severe pain preventing strength exercises
• Cognitive impairment that renders the informed consent process impossible.

Related Conditions & MeSH terms

• Fall
• Falls
• Frailty
• Frailty Syndrome

Intervention

Drug:
• Nicotinamide
The subjects will receive 1.5 grams per day of Nicotinamide, orally, for 30 days.
• Placebo
The subjects will receive 1.5 grams per day of placebo, orally, for 30 days.

Locations

Country	Name	City	State
Chile	Hospital Clínico Universidad de Chile	Santiago

Sponsors (3)

Lead Sponsor	Collaborator
University of Chile	Center for Advanced Clinical Research (CICA ) - University of Chile, Centro FONDAP de Gerociencia, Salud mental y Metabolismo (GERO)

Country where clinical trial is conducted

Chile, 

References & Publications (19)

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Alvarez C, Ramirez-Campillo R, Ramirez-Velez R, Izquierdo M. Effects and prevalence of nonresponders after 12 weeks of high-intensity interval or resistance training in women with insulin resistance: a randomized trial. J Appl Physiol (1985). 2017 Apr 1;122(4):985-996. doi: 10.1152/japplphysiol.01037.2016. Epub 2017 Feb 2. — View Citation

Ambrose AF, Paul G, Hausdorff JM. Risk factors for falls among older adults: a review of the literature. Maturitas. 2013 May;75(1):51-61. doi: 10.1016/j.maturitas.2013.02.009. Epub 2013 Mar 22. — View Citation

Angulo J, El Assar M, Alvarez-Bustos A, Rodriguez-Manas L. Physical activity and exercise: Strategies to manage frailty. Redox Biol. 2020 Aug;35:101513. doi: 10.1016/j.redox.2020.101513. Epub 2020 Mar 20. — View Citation

Chen Y, Zhang Y, Guo Z, Bao D, Zhou J. Comparison between the effects of exergame intervention and traditional physical training on improving balance and fall prevention in healthy older adults: a systematic review and meta-analysis. J Neuroeng Rehabil. 2021 Nov 24;18(1):164. doi: 10.1186/s12984-021-00917-0. — View Citation

Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021 Feb;22(2):119-141. doi: 10.1038/s41580-020-00313-x. Epub 2020 Dec 22. — View Citation

Cruz-Jentoft AJ, Sayer AA. Sarcopenia. Lancet. 2019 Jun 29;393(10191):2636-2646. doi: 10.1016/S0140-6736(19)31138-9. Epub 2019 Jun 3. Erratum In: Lancet. 2019 Jun 29;393(10191):2590. — View Citation

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Hwang ES, Song SB. Possible Adverse Effects of High-Dose Nicotinamide: Mechanisms and Safety Assessment. Biomolecules. 2020 Apr 29;10(5):687. doi: 10.3390/biom10050687. — View Citation

Ji LL, Yeo D. Maintenance of NAD+ Homeostasis in Skeletal Muscle during Aging and Exercise. Cells. 2022 Feb 17;11(4):710. doi: 10.3390/cells11040710. — View Citation

Knip M, Douek IF, Moore WP, Gillmor HA, McLean AE, Bingley PJ, Gale EA; European Nicotinamide Diabetes Intervention Trial Group. Safety of high-dose nicotinamide: a review. Diabetologia. 2000 Nov;43(11):1337-45. doi: 10.1007/s001250051536. — View Citation

Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe. Cell. 2023 Jan 19;186(2):243-278. doi: 10.1016/j.cell.2022.11.001. Epub 2023 Jan 3. — View Citation

Loureiro V, Gomes M, Loureiro N, Aibar-Almazan A, Hita-Contreras F. Multifactorial Programs for Healthy Older Adults to Reduce Falls and Improve Physical Performance: Systematic Review. Int J Environ Res Public Health. 2021 Oct 15;18(20):10842. doi: 10.3390/ijerph182010842. — View Citation

Preyat N, Rossi M, Kers J, Chen L, Bertin J, Gough PJ, Le Moine A, Rongvaux A, Van Gool F, Leo O. Intracellular nicotinamide adenine dinucleotide promotes TNF-induced necroptosis in a sirtuin-dependent manner. Cell Death Differ. 2016 Jan;23(1):29-40. doi: 10.1038/cdd.2015.60. Epub 2015 May 22. — View Citation

Rodrigues F, Domingos C, Monteiro D, Morouco P. A Review on Aging, Sarcopenia, Falls, and Resistance Training in Community-Dwelling Older Adults. Int J Environ Res Public Health. 2022 Jan 13;19(2):874. doi: 10.3390/ijerph19020874. — View Citation

Sherrington C, Fairhall NJ, Wallbank GK, Tiedemann A, Michaleff ZA, Howard K, Clemson L, Hopewell S, Lamb SE. Exercise for preventing falls in older people living in the community. Cochrane Database Syst Rev. 2019 Jan 31;1(1):CD012424. doi: 10.1002/14651858.CD012424.pub2. — View Citation

Sun M, Min L, Xu N, Huang L, Li X. The Effect of Exercise Intervention on Reducing the Fall Risk in Older Adults: A Meta-Analysis of Randomized Controlled Trials. Int J Environ Res Public Health. 2021 Nov 29;18(23):12562. doi: 10.3390/ijerph182312562. — View Citation

Tsao YL, Hsu CC, Chen KT. Blunt Traumatic Retropharyngeal Hematoma with Respiratory Symptoms: A Systematic Review of Reported Cases. Emerg Med Int. 2021 Oct 7;2021:5158403. doi: 10.1155/2021/5158403. eCollection 2021. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in physical performance	Assess the change in total Short Physical Performance Battery (SPPB) performance from baseline to post-4 weeks	Four weeks
Secondary	Posturography	Change Center of pressure (COP) between baseline and post-training in posturography	Four weeks
Secondary	Dynamometry	Change in dynamometry performance between baseline and post-training	Four weeks
Secondary	Quadriceps saturation	Change in quadriceps saturation after a 5-squat test	Four weeks
Secondary	Adherence to medication	Nicotinamide/placebo usage via self-report survey	Four weeks
Secondary	Adverse effects	Assessment of adverse effects using a standardized evaluation guideline.	Four weeks
Secondary	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