Table 2 Summary of published clinical trials on Sirtuin activators
Trial [ref] | Year | Phase | Participant | Intervention/ Comparison | Sample size of intervention/ comparison | Outcome | Main Findings |
|---|---|---|---|---|---|---|---|
NCT022459321056 | 2020 | N/A | COPD | • Resveratrol (150 mg/day) • Placebo (for 4 weeks) | 11/10 | Mitochondrial function | Muscle mitochondrial biogenesis regulators SIRT1 was not improved by resveratrol. An unexpected decline was shown in lean mass with resveratrol supplementation in patients with COPD |
IRCT20181029041490N1978 | 2019 | N/A | Patients with T2D and CHD | • Resveratrol (500 mg/day) • Placebo (for 4 weeks) | 28/28 | IR | Resveratrol upregulated PPAR-γ and SIRT1 in PBMC of T2DM patients with CHD |
IRCT201511233664N161058 | 2018 | N/A | NAFLD patients | • The CR diet (prescribed low-calorie diet) • Resveratrol (600 mg/day) • Placebo capsules (600 mg/day starch, for 12 weeks) | 30/30/30 | Anthropometric indices, metabolic parameters, and serum SIRT1 levels | No significant changes were seen in SIRT1 levels in any group |
NCT016688361052 | 2018 | N/A | Healthy subjects | • Resveratrol (500 mg/day) • CR (1000 cal/day, for 30 days) | 24/24 | Gene expression of SIRT1 and endogenous secretory receptor | Both resveratrol supplementation and CR stimulated SIRT1 serum concentrations |
NCT022448791054 | 2018 | N/A | T2D patients | • Resveratrol (500 mg/day) • Resveratrol (40 mg/day) • Placebo (inert microcellulose) for 6 months | 43/43/42 | Association between changes in SIRT1 level and variation in H3K56ac value | Increased SIRT1 expression was associated with significant H3K56ac content reduction and increased serum antioxidant activity in T2D patients. SIRT1-mediated changes in the epigenome and in the antioxidant, response might impact on diabetes-associated risk factors |
NCT015048547 | 2017 | II | Mild-moderate AD patients | • Resveratrol (500 mg orally once daily and a dose escalation by 500-mg increments every 13 weeks, ending with 1000 mg twice daily) • Placebo (matching placebo, for 52 weeks) | 19/19 | Safety and tolerability as well as effects on AD biomarkers and volumetric MRI | Resveratrol decreases CSF MMP9, modulates neuro-inflammation, and induces adaptive immunity. SIRT1 activation may be a viable target for treatment or prevention of neurodegenerative disorders |
NCT01031108990 | 2017 | I | T2D patients | • Oral SRT2104 (2.0 g/day) • Placebo (Sirtris Pharmaceuticals 2.0 g/day, for 28 days) | 15/14 | Pharmacokinetics of SRT2014; Cardiovascular effects of SRT2104; Endogenous fibrinolysis and monocyte and platelet activation; Metabolic effects | Short-term SIRT1 activation in humans is well tolerated and has predominantly neutral effects on markers of endothelial function and platelet-monocyte function |
NCT014534911061 | 2016 | N/A | Patients with mild to moderate UC | • SRT2104 (500 mg/day) • SRT2104 (50 mg/day, for 8 weeks) | 13/13 | Colonic exposure, safety, and clinical activity of SRT2104 | SRT2104 did not demonstrate significant clinical activity in mild to moderately active UC |
NCT01031108991 | 2016 | I | Healthy cigarette smokers and T2D patients | • Oral SRT2104 (2.0 g/day) • Placebo (2.0 g/day, for 28 days) | 11/13 (healthy cigarette smokers);7/8 (T2D patients) | Pulse wave analysis and velocity; blood pressure | Compared to placebo, treatment with SRT2104 was associated with a significant reduction in augmentation pressure. SRT2104 may improve arterial compliance in otherwise healthy cigarette smokers and in people with T2D, without affecting resting measures of blood pressure |
NCT016688361053 | 2016 | N/A | Healthy participants | • Resveratrol (500 mg/day) • Low-calorie diet (1000 cal/day, for 30 days) | 24/24 | Serum lipid parameter, glucose, insulin, oxidative stress, C-reactive protein, and SIRT1 | CR and resveratrol significantly increased plasma concentrations of SIRT1 |
NCT011541011097 | 2015 | IIa | Stable plaque-psoriasis | • SRT2104 (250 mg/day) • SRT2104 (500 mg/day) • SRT2104 (1000 mg/day) • Placebo, for 84 consecutive days | 9/12/11/7 | The change in histological assessments of skin biopsies of psoriatic lesions; the assessment of effect of SRT2104 on Psoriasis Area Severity Index and Physician Global Assessment scores in patients with moderate to severe plaque psoriasis | Substantial improvement was found in 9 subjects following 84 days of treatment with SRT2104. Although absorption was relatively linear with dose, we did not observe a dose-response in the histology endpoint |
NCT010141171055 | 2015 | N/A | Healthy, nonsmoking, male volunteers | • SRT2104 (2.0 g/day) • Placebo on days 1–6 and SRT2104 (2.0 g) on day 7 • Placebo, for seven consecutive days | 8/8/8 | LPS-induced IL-6 and IL-8 release; LPS-induced coagulation; LPS-induced leukocyte transcriptional responses | SRT2104 attenuated LPS-induced release of the cytokines IL-6 and IL-8. SRT2104 also reduced the LPS-induced acute phase protein response (C-reactive protein). SRT2104 inhibited activation of coagulation, as reflected by lower plasma levels of the prothrombin fragment F1 + 2. Activation of the vascular endothelium and the fibrinolytic system was not influenced by SRT2104 |
EudraCT number 2009-010720-261098 | 2014 | II | T2D patients | • SRT2104 (0.25 g/day) • SRT2104 (0.5 g/day) • SRT2104 (1.0 g/day) • SRT2104 (2.0 g/day) • Placebo (once daily, for 28 days) | 45/46/45/45/46 | Changes in fasting and post-prandial glucose and insulin | Treatment with SRT2104 for 28 days did not result in improved glucose or insulin control. Treatment with SRT2104 was associated with improvement in lipid profiles |
NCT011509551059 | 2014 | N/A | Obese males | • Trans-resveratrol (500 mg three times per day) • Placebo (three times per day, for 5 weeks) | 12/12 | Effect of body composition and age on GH-stimulated STAT5b phosphorylation and IGF-1, SOCS2, and CISH mRNA in muscle and fat; The impact of resveratrol treatment on GH activity; Impact of inhibiting or knocking down SIRT1 on effects of GH in vitro. | Resveratrol administration had no impact on body composition, serum IGF-1, or GH signaling in vivo, and SIRT1 knock down or inhibition did not affect GH signaling in vitro |
NCT011509551060 | 2013 | N/A | Obese but otherwise healthy men | • Trans-resveratrol (500 mg thrice daily) • Placebo (thrice daily, for 4 weeks) | 12/12 | Insulin sensitivity | Short-term supplementation with high-dose resveratrol is not associated with detectable physiological effects in obese subjects with modest IR |
NCT010311088 | 2013 | I | Healthy volunteers | • SRT2104 (2.0 g/day) • Placebo (Sirtris Pharmaceuticals Inc, for 28 days) | 24 (cross-over) | Lipid profile and vascular, endothelial, and platelet function | Compared with placebo, serum lipid profile improved during SRT2104 administration, with reductions in serum TC, LDL-C, and TG concentrations. SIRT1 activation may have a beneficial role in patients at risk of developing or with established cardiovascular disease |
NCT008233811057 | 2012 | N/A | Non-obese, postmenopausal women | • Resveratrol supplementation (75 mg/day) • CR targeted to achieve a 5% weight loss within 12 weeks • Placebo, for 12 weeks | 15/15/14 | Metabolic function | Resveratrol did not affect its putative molecular targets, including AMPK and SIRT1, in either skeletal muscle or adipose tissue |
