Potential beneficial effect of nicotinamide mononucleotide in older adults with COVID-19 infection.
Summary
Joint Investigators: Jeanne Wei (PI, Geriatrics), Manish Joshi (Pulmonary and Critical Care), Ruofei Du (COPH), Elizabeth Eoff (Trainee, Geriatrics)
Background
An exaggerated inflammatory response to the SARS-CoV-2 virus is a major contributor to increased morbidity, prolonged recovery (up to 6-9 months), and high fatality in elderly patients.
Several potential interventions to dampen the inflammatory response and the associated “cytokine excess” have been proposed; they include hydroxychloroquine, glucocorticoids, and selective cytokine blockers such as tocilizumab and remdesivir. Another potential factor, nicotinamide mononucleotide (NMN) is attractive because it increases nicotinamide adenine dinucleotide (NAD ), which modulates the NOD-like receptor family and dampens the release of inflammatory cytokines during infection. Nicotinamide adenine dinucleotide is critical for normal immune system function during infections because it is used as fuel for enzyme families that regulate the immune responses [e.g., poly (ADP-ribose) polymerases (PARPs), sirtuins, CD38]. Older adults have reduced basal NAD levels, due partly to reduced synthesis and increased degradation by a NAD degrading enzyme, CD38. In addition, NAD levels in the lung, cardiovascular system, muscles and other tissues are further depleted by the SARS-CoV-2 infection. This results in prolonged weakness, fatigue and functional decline in older adults.
NMN administration has been shown to safely increase NAD levels in older adults. We hypothesize that activation of the sirtuin-NAD pathway by administration of NMN may reduce the inflammatory response in tissues post-COVID19 infection and enhance a more rapid recovery in older adults.
Primary Aim
To test whether it may be feasible to administer NMN to post-COVID patients and assess the functional effects.
Secondary aims
To determine whether NMN vs placebo therapy will be associated with:
- Reduced pro-inflammatory factors (IL6, IL1β, TNFα, CRP, ESR, procalcitonin);
- Greater improvement in endothelial function with better forearm blood flow compared to placebo.
Study Participants n=60
All COVID-19 infected patients, who did not require intubation or dialysis during hospitalization will be eligible post-discharge. The patients who received anti-viral or other drugs during hospitalization will be allowed to participate. Age: 55-89 years; both males and females, all races and ethnicities.
Participant Allocation: The subjects will be allocated to the NMN or placebo arms by a stratified randomization.
Intervention: nicotinamide mononucleotide (NMN) vs placebo for 90 days.
Study Procedures Informed consent will be obtained from Covid-19 treated subjects before discharge. Subjects will undergo baseline blood tests and functional assessment within 10-14 days of hospital discharge or for those not , within 10-14 days after receiving treatment at home. Subjects will be stratified at age 70 (55-70, 71-89) and then randomly assigned to either placebo or NMN arm (1:1 ratio) and will take 500 mg NMN or placebo tablets once daily for 90 days. At the end of 90 days, blood tests and functional assessment will be repeated. Functional assessments will include handgrip strength and 6 min walking distance . Forearm blood flow will be evaluated by impedance plethysmography for endothelial function. Blood measurements will include blood tests for pro-inflammatory cytokines and factors.
Keywords:
- adverse events
- Health Care
- lung injury
- Translational Research
- patient safety
- molecular profiling
- Medication
- Mitochondria
- Muscle adaptation
- Community
Researchers:
- Jeanne Wei (Author)
- Manish Joshi
- Ruofei Du
- Elizabeth Eoff