SIRT6 Clinical Trials: Human Evidence, Forvisirvat & Fucoidan Studies

SIRT6 has crossed from preclinical biology into human research, but the human programs are easy to mix together. Synthetic forvisirvat/SP-624 directly targets SIRT6 and has completed multiple psychiatric drug trials. Fucoidan-based SIRT6Activator is being studied in healthy-aging protocols. Other fucoidan trials measure fatigue, inflammation or metabolic outcomes without proving SIRT6 target engagement.

Those are three different evidence layers. This page tracks them separately and reports registry status as of September 21, 2026.

Study	Intervention	Population	Current status	What it can tell us
SP-624 Phase 1	SP-624 / forvisirvat	Healthy adults	Published	Short-term safety, tolerability and pharmacokinetics of a direct SIRT6 activator
NCT04510298	SP-624	27 adults with acute schizophrenia	Completed	Safety/PK and exploratory psychiatric effects
NCT04479852	Forvisirvat 20 mg/day	319 randomized adults with MDD	Published	Direct randomized efficacy test; primary endpoint negative overall
NCT06570369	SP-624 vs placebo	26 healthy adults/adults with MDD	Completed May 2026	EEG brain-network, safety and exploratory cognitive effects
NCT06254612	SP-624 20 mg/day vs placebo	497 adults with MDD	Completed July 2026; no results posted	Larger confirmatory psychiatric efficacy/safety dataset when reported
PROMETHEUS — NCT07451496	SIRT6Activator® 2.4 g/day inside a multimodal program	20 middle-aged/older adults	Registry still says Recruiting; no results posted	Feasibility/safety of a combined geroscience protocol, not isolated SIRT6Activator efficacy
Project SIRT6 Activator — NCT07500649	Fucoidan/SIRT6 activator 2.4 g/day vs placebo	60 prefrail men aged 50–80	Recruiting	Most direct randomized test of fucoidan for a biological-aging endpoint
NCT06295588	F. vesiculosus fucoidan 4 g/day	Cancer survivors with fatigue	Recruiting	Human fucoidan fatigue/inflammation/frailty evidence; not a SIRT6-target-engagement trial

First distinction: direct SIRT6 trials vs fucoidan trials

A trial can involve a compound associated with SIRT6 without proving that SIRT6 caused the outcome.

Forvisirvat/SP-624 is a designed small molecule developed specifically as a SIRT6 activator. Its human program therefore gives the cleanest evidence about direct pharmacological SIRT6 targeting.

Fucoidan is a heterogeneous marine polysaccharide with many biological actions. Specific preparations activate SIRT6 in biochemical and preclinical studies, but a human fucoidan trial only becomes strong SIRT6 evidence if it also demonstrates target engagement or SIRT6-dependent biology.

Published Phase 1: SP-624 in healthy adults

The published Phase 1 program combined randomized, double-blind, placebo-controlled single- and multiple-ascending-dose studies in healthy adults [1].

Single oral doses of 3, 10 and 30 mg and repeated dosing up to 20 mg/day were evaluated. Plasma exposure increased approximately with dose, and predicted target concentrations were reached. No serious adverse events were reported in these short studies.

A high-fat meal lowered peak concentration and delayed the time to peak while overall exposure was broadly comparable. The trials therefore established oral exposure and short-term tolerability—not anti-aging efficacy, long-term safety or human lifespan benefit.

The paper's conflict-of-interest context matters: authors included consultants to the developing company with minority equity interests.

NCT04510298: Phase 1B in acute schizophrenia

This four-week randomized, double-blind, placebo-controlled inpatient study enrolled 27 adults with acute schizophrenia. It evaluated safety, population pharmacokinetics and exploratory efficacy of SP-624.

The trial is completed. It is useful evidence that SP-624 was administered in a psychiatric patient population, but it was not an aging study and does not establish geroscience benefit.

View NCT04510298.

NCT04479852: published Phase 2 major-depression trial

The published Phase 2 study randomized 319 adults with moderate-to-severe major depressive disorder to forvisirvat 20 mg/day or placebo for four weeks; 317 received treatment [2].

Primary result

Forvisirvat did not significantly outperform placebo on the prespecified primary endpoint, change in Montgomery–Åsberg Depression Rating Scale score at Week 4.

Post-hoc sex signal

Post-hoc analyses suggested greater benefit in women and no comparable signal in men. That finding is interesting but hypothesis-generating. It cannot be promoted as established sex-specific efficacy until prospectively confirmed.

Safety

No serious adverse events were reported among forvisirvat-treated participants in the published trial. The treatment period was only four weeks, so this is not long-term safety evidence.

NCT06254612: larger Phase 2B study completed in 2026

This is now one of the most important unpublished datasets in the SIRT6 field. The updated registry-derived record lists the study as Completed, with 497 participants and completion on July 8, 2026. Participants received SP-624 20 mg/day or matching placebo in a randomized, fully blinded parallel design.

No efficacy results have been publicly posted as of September 21, 2026. Older trial mirrors still show earlier recruiting/enrollment estimates, so they should not be used to overwrite the newer August 2026 registry update.

Until results are released, the correct statement is simply that the study completed—not that it confirmed, failed to confirm or replicated the earlier female subgroup finding.

View NCT06254612.

NCT06570369: completed Phase 1 brain-network study

This 26-participant randomized study tested SP-624 or placebo once daily for two weeks in healthy adults and adults with major depressive disorder. The primary outcome used EEG-based Brain Network Analytics, with exploratory learning and memory measures in participants with depression.

The record was updated in May 2026 as Completed. Results have not established a neuroprotective or anti-aging effect.

View NCT06570369.

PROMETHEUS: important, but not a standalone SIRT6Activator trial

The 2026 peer-reviewed PROMETHEUS protocol includes DoNotAge.org SIRT6Activator® at 2.4 g/day within an eight-week personalized multimodal geroscience program [3].

The intervention also includes sleep and dietary counseling, supervised exercise/exergaming, motivational interviewing, whey protein and creatine. Depending on gerotype and interim response, augmented interventions can include NMN, urolithin A, a multivitamin/mineral and ergothioneine.

This means PROMETHEUS can assess the feasibility, adherence, safety and exploratory effect of the combined program. It cannot isolate the effect of SIRT6Activator.

A registry-status nuance that matters

The ClinicalTrials.gov record still lists PROMETHEUS as Recruiting and was last updated March 5, 2026. At the same time, it lists an actual primary completion date of February 23, 2026 and an estimated study completion date of June 30, 2026, which has passed. No results are posted.

The defensible interpretation is that the public record appears administratively stale. We should report the registry exactly rather than silently upgrading the trial to “completed” or implying positive results.

View PROMETHEUS.

Project SIRT6 Activator: the cleanest current fucoidan aging RCT

NCT07500649 is the most directly relevant human study for the supplement/healthy-aging question.

• Sponsor: National University of Singapore.
• Collaborators: University of Rochester, L'Oréal and DoNotAge.org.
• Population: 60 prefrail men aged 50–80.
• Intervention: 2.4 g/day fucoidan described by the registry as SIRT6 activator.
• Comparator: placebo.
• Design: randomized, parallel, quadruple-masked.
• Duration: six months.
• Primary outcome: change in blood DNA-methylation biological age/GrimAge.
• Status: Recruiting as of September 2026.

The planned primary completion is March 31, 2027 and full completion December 31, 2027.

Even a positive epigenetic-clock result would need careful interpretation. A clock change is not the same as fewer age-related diseases, preserved function or longer lifespan.

NCT06295588: useful fucoidan human evidence, not direct SIRT6 proof

The University of Rochester is also running a randomized Phase 2 supportive-care trial in cancer survivors with fatigue. Participants initially receive either usual care or 4 g/day of Fucus vesiculosus fucoidan for eight weeks; outcomes include fatigue, inflammatory markers and frailty. The trial remains recruiting, with completion listed for December 2026.

This is relevant to oral fucoidan exposure and human tolerability. It is not a SIRT6 target-engagement trial, so a future effect on CRP or fatigue should not automatically be attributed to SIRT6.

View NCT06295588.

What human evidence is still missing?

• Direct demonstration that an oral natural activator increases SIRT6 catalytic activity in relevant human tissue.
• A completed randomized SIRT6-targeted aging trial with a clinically meaningful outcome.
• Long-term safety data for chronic systemic activation.
• Replication of any biological-age effect across independent clocks and cohorts.
• Evidence that biomarker changes translate into better function, less disease or longer survival.
• A clear human dose-response relationship for fucoidan-mediated SIRT6 activation.

Bottom line

The human SIRT6 field is real but should not be overstated. Forvisirvat proves that a direct SIRT6 activator can reach human clinical development; it does not prove aging efficacy. The first published Phase 2 trial was negative on its primary endpoint overall, a larger 497-person study has completed without public results, and additional CNS studies are complete.

On the natural-product side, human aging translation is underway. PROMETHEUS includes SIRT6Activator but cannot isolate it; Project SIRT6 Activator is the more informative randomized trial and is still recruiting.

See SIRT6 activators for pharmacology, dosage for studied amounts and fucoidan/SIRT6 evidence for the exact ingredient chain.