Disease: Dementia/Aging
Type of study: Interventional trial
Coordinating investigator: Katarina Lundervold
Study directors: Charalampos Tzoulis & Bettina Husebø
Background: 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 multisystem 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 diseasespecific 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, a phase II double-blinded randomised clinical trial of oral NR in ageing-related frailty.
The primary objective of the NADage study is to determine whether treatment with NR, 2000 mg daily, can increase intrinsic capacity in a communitydwelling 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.
Design: NADage, a phase II double-blinded randomised clinical trial of oral NR, 2000 mg per day, in older individuals with mild to moderate frailty. NADage will recruit a total of 100 participants from all over Norway. Study duration will be one year.
Primary endpoint: The between-group difference in the change in gait speed from baseline to week 52 as assessed by the 6-minute walk test (and concurrent sensor-based gait speed assessment) in a community dwelling frail older population.
Status: The study protocol is completed, and necessary approvals obtained. Recruitment will start in 2025.
Participating centre
- Haukeland University Hospital, Bergen
Funding
- The Rieber Foundation
- The University of Bergen
- The Research Council of Norway, Neuro-SysMed
- Haukeland University Hospital