What clinical trials are planned or underway to test P7C3‑A20 or NAD+‑modulating therapies in humans?
Executive summary
P7C3‑A20 has compelling and recent preclinical data showing restoration of NAD+ homeostasis and reversal of severe pathology in multiple animal models, but no human clinical trials of P7C3‑A20 were reported in the provided sources and the literature calls for careful translational work before first‑in‑human testing [1] [2] [3]. By contrast, a growing and active clinical landscape exists for NAD+‑modulating therapies (NR, NMN and other precursors, and investigational delivery routes), with multiple small randomized trials completed and numerous ongoing studies testing safety, target engagement and early efficacy in aging, neurodegeneration, long COVID and metabolic conditions [4] [5] [6].
1. P7C3‑A20: promising animal science but no human trials yet
The December 2025 Cell Reports Medicine paper and related preclinical studies document robust reversal of advanced Alzheimer’s‑like pathology and cognitive recovery in multiple mouse and nonhuman primate experiments treated with P7C3‑A20, and the authors explicitly call for “carefully designed human clinical trials” to test translation to patients [1] [2] [7]. However, none of the supplied sources report an active or planned Phase 1 or first‑in‑human study of P7C3‑A20; the journalism and university press releases reiterate the need to move into human trials but do not announce a trial registry entry or sponsor [8] [2]. Importantly, mechanistic and safety signals—such as concentration‑dependent neurotoxicity seen in some in vitro preparations—are flagged as reasons to proceed cautiously before human dosing [3].
2. NAD+ precursors: an established human trial portfolio
Clinical testing of NAD+‑modulating compounds—principally nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), plus formulations and IV approaches—has already reached human randomized trials and expanded into condition‑specific pilot studies; systematic reviews summarize dozens of trials and ongoing studies seeking to define safety, bioavailability and biomarker changes [4] [6] [9]. Examples in the provided material include randomized trials showing that NR increases the NAD+ metabolome and alters inflammatory signatures and transcriptomes in muscle and blood [10], NMN trials reporting improved insulin sensitivity in older prediabetic women [11], and a double‑blind crossover showing that a systems‑designed supplement raised whole‑blood NAD+ [12].
3. Ongoing and recent human trials of NAD+ strategies: areas and modalities
The current clinical pipeline spans neurodegeneration (Parkinson’s and Alzheimer’s), long‑COVID, cardiometabolic health and aging itself; recent and ongoing trials include NR in long‑COVID (reported randomized RCT with exploratory cognitive/symptom signals), NR safety/dosing studies in Parkinson’s (NR‑SAFE), IV NAD+/NR pilot studies to test delivery and tolerability, and multiple NMN oral studies with metabolic endpoints—while reviews note “numerous trials currently underway” to extend duration, target populations and biomarkers [13] [14] [10] [6] [5]. These trials are predominantly early‑phase, focused on target engagement (raising NAD+), pharmacodynamics and short‑term biomarkers rather than large, long‑term disease‑modifying outcomes [5] [15].
4. What's known about safety, efficacy signals and limits of evidence
Human trials reliably show that oral NR and NMN increase blood NAD+ and can modulate inflammatory markers, but functional clinical benefits in aging, cognition or hard disease endpoints remain limited and heterogeneous across studies, prompting calls for larger, longer, better‑powered trials with tissue‑specific biomarkers and isotope tracer studies to understand NAD+ flux [10] [16] [6]. Reviews caution that supplement marketing often outpaces evidence and that supraphysiologic NAD+ elevation (reported with some over‑the‑counter boosters in animals) entails theoretical cancer risks—an argument used by P7C3 researchers to emphasize their compound’s homeostasis‑preserving mechanism versus indiscriminate boosting [1] [17] [16].
5. Bottom line and the translational gap
The translational pathway for NAD+ biology is active in humans: multiple precursors and delivery methods are already in early clinical testing with many trials ongoing [6] [5], but P7C3‑A20 itself remains a preclinical success story without an announced human Phase 1 in the sources provided and with specific mechanistic and toxicity questions that researchers say must be resolved before human dosing [1] [3]. Stakeholders should watch for formal trial registrations and Phase 1 protocols from academic sponsors or biotech spinouts tied to the Pieper lab work, while interpreting current NAD+ human data as encouraging for target engagement but not yet definitive for disease reversal in people [2] [5].