The NADage Study
NADage is a phase II randomized controlled trial of nicotinamide riboside (NR) in aging-related frailty. Here, the aim is to determine whether treatment with NR can increase intrinsic capacity in a community-dwelling older population living with frailty, including assessment of cognitive function and overall quality of life. This is a study headed by Neuro-SysMed, and financed by the G.C. Rieber Foundation, the University of Bergen, the Research Council of Norway (Neuro-SysMed), Haukeland University Hospital, NutriBrain, and the DAM Foundation.
Main content
There are currently no treatments that can prevent pathological brain aging and cognitive decline in the elderly. Achieving this requires neuroprotective interventions during prodromal stages of the disease, i.e., while it is still possible to avert irreversible neurodegeneration and prevent clinical progression to dementia. We propose that this can be achieved by augmenting brain nicotinamide adenine dinucleotide (NAD)-metabolism in the non-demented, elderly, frail population.
Frailty is defined as a geriatric syndrome of multi-system physiological deterioration, which is closely associated with pathological brain aging and a significantly increased risk of dementia, including mild cognitive impairment (MCI), Alzheimer’s disease (AD) and vascular dementia. Frailty may therefore be considered a precursor state to cognitive disorders, offering a therapeutic window for disease prevention. The ideal preventive strategy during this window would involve agents that not only enhance general neuronal resilience but also bolster resistance to disease-specific stressors, while being safe and suitable for long-term use in individuals at risk of cognitive disorders. We propose that this can be achieved through NAD-replenishment therapy, employing oral precursors such as nicotinamide riboside (NR). To test this hypothesis, we are conducting NADage study.
The primary objective of the NADage study is to determine whether treatment with NR, 2000 mg daily, can increase intrinsic capacity in a community-dwelling older population living with frailty, as measured by the change from baseline to week 52 in the 6-minute walk test (6MWT). Secondary objectives include assessment of cognitive function and overall quality of life.
NADage will recruit a total of 100 participants from all over Norway. The study duration will be one year. 2000 mg NR will be administered orally per day, versus placebo, in older individuals with mild to moderate frailty.
Team
NADage involves a comprehensive team across Neuro-SysMed, Centre for Elderly and Nursing Home Medicine (SEFAS) and Haraldsplass Deaconess Hospital. Co-Director at Neuro-SysMed, Professor Charalampos Tzoulis, is the study director, with PhD candidate Katarina Lundervold as coordinator. Professor Bettina S. Husebø is scientific advisor for the project, as is Senior Researcher Christian Dölle. PhD Candidate Haakon Berven is onboard as investigator, as is Associate Professor and Geriatrician Ragnhild Skogseth Eide and Consultant Neurologist Kristoffer Haugarvoll. Study nurses are Mona Søgnen and Erika Veslemøy Sheard. Bård Erik Bogen, Astri J. Lundervold, and Jörg Assmus have contributed as scientific advisors in the project planning.
Societal impact
The NADage study has the potential to significantly impact society by offering a promising intervention for age-related frailty, a condition closely linked to cognitive decline and dementia. If successful, the research could lead to an accessible, preventive treatment for older adults, enhancing their quality of life, cognitive function, and overall well-being, while also potentially reducing the societal burden of dementia and long-term care.
Current status
The study protocol is completed, and necessary approvals are obtained. Recruitment of participants has started. We expect to reach inclusion of half of the participants during 2025.