NADPARK Phase 1

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Brage Brakedal, Charalampos Tzoulis and colleagues, Haukeland University Hospital and University of Bergen. Cell Metabolism 34(3):396–407, 2022.

What happened

Brain energy failure (landmark 11) includes low NAD, a molecule cells need to make energy. NADPARK was a double-blind, randomised Phase 1 trial of nicotinamide riboside (a vitamin B3 form), 1,000 mg daily for 30 days versus placebo, in 30 newly diagnosed, treatment-naive people (registry dates March 2019 to February 2020). It was well tolerated and raised brain NAD (measured by 31P magnetic resonance spectroscopy) significantly but variably, and raised NAD-related metabolites in spinal fluid. In those whose brain NAD rose, FDG-PET showed altered brain metabolism, which was associated with mild clinical improvement. NR also lowered inflammatory cytokines in blood and spinal fluid.

Why it moved us toward a cure

It showed a supplement could reach the brain and change its chemistry, justifying the 410-person Phase 3 landmark 172 and the higher-dose safety study landmark 247. NOPARK then found no benefit, so raising brain NAD alone was not the answer.

Outcome

Advanced to Phase 3, which failed. The study was not designed to test slowing.

Sources

• Brakedal et al., Cell Metab 2022, DOI 10.1016/j.cmet.2022.02.001, PMID 35235774
• ClinicalTrials.gov NCT03816020 (NADPARK; API, 19 Oct 2026: completed, 30 enrolled, phase listed "not applicable", no results posted). The earlier NCT05589766 cited here is N-DOSE, a different trial (landmark 210).
• Not yet verified: effect sizes and P values (abstract only read); the full paper.