Towards personalized nicotinamide mononucleotide (NMN) supplementation: Nicotinamide adenine dinucleotide (NAD) concentration.

Nicotinamide mononucleotide (NMN) is a precursor of nicotinamide adenine dinucleotide (NAD), which declines with age. Supplementation of NMN has been shown to improve blood NAD concentration. However, the optimal NMN dose remains unclear. This is a post-hoc analysis of a double-blinded clinical trial involving 80 generally healthy adults aged 40-65 years. The participants received a placebo or daily 300 mg, 600 mg, or 900 mg NMN for 60 days. Blood NAD concentration, blood biological age, homeostatic model assessment for insulin resistance, 6-minute walk test, and 36-item short-form survey (SF-36) were measured at baseline and after supplement. A significant dose-dependent increase in NAD concentration change (NADΔ) was observed following NMN supplementation, with a large coefficient of variation (29.2-113.3%) within group. The increase in NADΔ was associated with an improvement in the walking distance of 6-minute walk test and the SF-36 score. The median effect dose of NADΔ for the 6-minute walk test and SF-36 score was 15.7 nmol/L (95% CI: 10.9-20.5 nmol/L) and 13.5 nmol/L (95% CI; 10.5-16.5 nmol/L), respectively. Because of the high interindividual variability of the NADΔ after NMN supplementation, monitoring NAD concentration can provide valuable insights for tailoring personalized dosage regimens and optimizing NMN utilization.

The efficacy and safety of ß-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial.

In animal studies, ß-nicotinamide mononucleotide (NMN) supplementation increases nicotinamide adenine dinucleotide (NAD) concentrations and improves healthspan and lifespan with great safety. However, it is unclear if these effects can be transferred to humans. This randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial included 80 middle-aged healthy adults being randomized for a 60-day clinical trial with once daily oral dosing of placebo, 300 mg, 600 mg, or 900 mg NMN. The primary objective was to evaluate blood NAD concentration with dose-dependent regimens. The secondary objectives were to assess the safety and tolerability of NMN supplementation, next to the evaluation of clinical efficacy by measuring physical performance (six-minute walking test), blood biological age (Aging.Ai 3.0 calculator), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and subjective general health assessment [36-Item Short Form Survey Instrument (SF-36)]. Statistical analysis was performed using the Per Protocol analysis with significant level set at p = 0.05. All 80 participants completed the trial without trial protocol violation. Blood NAD concentrations were statistically significantly increased among all NMN-treated groups at day 30 and day 60 when compared to both placebo and baseline (all p ≤ 0.001). Blood NAD concentrations were highest in the groups taking 600 mg and 900 mg NMN. No safety issues, based on monitoring adverse events (AEs), laboratory and clinical measures, were found, and NMN supplementation was well tolerated. Walking distance increase during the six-minute walking test was statistically significantly higher in the 300 mg, 600 mg, and 900 mg groups compared to placebo at both days 30 and 60 (all p < 0.01), with longest walking distances measured in the 600 mg and 900 mg groups. The blood biological age increased significantly in the placebo group and stayed unchanged in all NMN-treated groups at day 60, which resulted in a significant difference between the treated groups and placebo (all p < 0.05). The HOMA-IR showed no statistically significant differences for all NMN-treated groups as compared to placebo at day 60. The change of SF-36 scores at day 30 and day 60 indicated statistically significantly better health of all three treated groups when compared to the placebo group (p < 0.05), except for the SF-36 score change in the 300 mg group at day 30. NMN supplementation increases blood NAD concentrations and is safe and well tolerated with oral dosing up to 900 mg NMN daily. Clinical efficacy expressed by blood NAD concentration and physical performance reaches highest at a dose of 600 mg daily oral intake. This trial was registered with ClinicalTrials.gov, NCT04823260, and Clinical Trial Registry - India, CTRI/2021/03/032421.

Recruiting ENT and Audiology patients into pharmaceutical trials: evaluating the multi-centre experience in the UK and USA.

OBJECTIVE: Recruiting into clinical trials on time and on target is a major challenge and yet often goes unreported. This study evaluated the adjustment to procedures, recruitment and screening methods in two multi-centre pharmaceutical randomised controlled trials (RCTs) for hearing-related problems in adults. DESIGN: Recruitment monitoring and subsequent adjustment of various study procedures (e.g. eligibility criteria, increasing recruiting sites and recruitment methods) are reported. Participants were recruited through eight overarching methods: trial registration, posters/flyers, print publications, Internet, social media, radio, databases and referrals. The efficiency of the recruitment was measured by determining the number of people: (1) eligible for screening as a percentage of those who underwent telephone pre-screening and (2) randomised as a percentage of those screened. STUDY SAMPLE: A total of 584 participants completed the pre-screening steps, 491 screened and 169 participants were randomised. RESULTS: Both RCTs completed adjustments to the participant eligibility, added new study sites and additional recruitment methods. No single recruitment method was efficient enough to serve as the only route to enrolment. CONCLUSION: A diverse portfolio of methods, continuous monitoring, mitigation strategy and adequate resourcing were essential for achieving our recruitment goals.