Table 2.
A Summary of Clinical Trials with NAD+ Precursors: Focusing on Cognitive Function and Neurodegenerative Diseases
| Disease | NAD+ Precursor | Dose and Treatment Duration | Main Endpoints | Status and Results | References/NCT |
|---|---|---|---|---|---|
| AD and MCI | NAM | 1,500 mg twice daily, orally for 48 weeks | effect on P-tau231 and total tau in CSF | recruiting, no results | |
| 1,500 mg twice daily for 6 months | Alzheimer’s Disease Assessment Scale-Cognitive Subscale (cognitive function) | completed, no effect reported | ; Phelan et al., 2017 | ||
| NR | dose escalation, 250–1,000 mg for 10 weeks | change in cognitive accessments, cerebral blood flow, plasma NAD levels, and physical performances in MCI patients | recruiting, no results | ||
| 500 mg twice daily for 12 weeks | memory, brian blood flow, and cognitive function | recruiting, no results | |||
| NADH | 10 mg/day for 8–12 weeks (i.v.) | cognitive score (MMSE) | completed, no effect on cognitive score | Rainer et al., 2000 | |
| cognitive score (MMSE) | completed, improved cognitive score | Birkmayer, 1996 | |||
| PD | NR | 1,000 mg/day for 52 weeks | MDS-UPDRS, levels of NAD metabolites in blood | not yet recruiting, no results | |
| 500 mg/day for 30 days | changes in PD related pattern, neurometabolic profile, and motor function | recruiting, no results | |||
| NA or NAM | 100 mg twice daily for 18 months | unified PD rating scale changes, cognitive function (MMSE), sleep, niacin changes, and inflammatory markers in CSF | not yet recruiting, no results | ||
| NADH | 25–50 mg/day, i.v. or i.m. | changes in PD-related disabilities, including movements | completed, benefits on PD-related disabilities like movement | Birkmayer et al., 1989, 1993 | |
| 25 mg/day/4 days i.v., after 2–4 weeks 25 mg/day/4 days i.m. | unified PD rating scale changes including disabilities and movements | completed, no effects of treatment | Dizdar et al., 1994 | ||
| ALS | EH301 | not published | ALS-FRSr Functional Rating Scale, MRC grading scale index, FVC, muscle activity, fat, and muscle weights | completed, improvements of at least 1 out of 3 clinical measures in all patients compared to placebo | ; de la Rubia etal., 2019 |
| A-T | NR | 25 mg/kg/day for 4 months | ataxia, dysarthria, quality of life, laboratory parameters, intelligibility, and fatigue status | enrolling by invitation, no results | |
| F-A | NAM | 4 g/day or highest tolerated dose (min. 2 g/day) for 1 year | ataxia, quality of life, progression of cerebellar severity, and safety issues | not yet recruiting, no results | |
| dose-escalation, 2–8 g for 9–12 months | level of frataxin, ataxia, and other clinical characteristics; identification of novel biomarkers; and determine safety and tolerability | unknown, no results | |||
| Axon denervation in healthy individuals | NR | 900 mg twice daily for 3 months, orally | denervation of skin and reinnervation of skin after experimental denervation with capsaicin | not yet recruiting, no results | |
| Cognitive function, mood, and sleep in healthy elderly | NR | 300 mg/day or 1,000 mg/day for 8 weeks | differences between low-dose treatment and placebo/baseline in executive function (CNS vital signs tests) | active, no results |
AD, Alzheimer’s disease; ALS, amytrophic lateral sclerosis; ALS-FRSr, ALS functional rating scale; A-T, ataxia telangiectasia; CNS, central nervous system; CSF, cerebrospinal fluid; EH301, drug consisting of a combination of 1-(b-D-Ribofuranosyl) nicotinamide chloride and 3,5-dimethoxy-40-hydroxy-transstilbene; F-A, Friedreich ataxia; FVC, functional respiratory capacity; i.m., intramuscularly; i.v., intravenously; MCI, mild cognitive impairment; MMSE, minimental state examination; MDS-UPDRS, Movement Disorder Society Unified Parkinson disease rating scale; MRC, Medical Research Council; NAM, nicotinamide; NMN, nicotinamide mononucleotide; NR, nicotinamide riboside; PD, Parkinson’s disease; P-Tau, phosphorylated Tau.