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 |
AD Alzheimer’s disease, AMPK adenosine monophosphate-activated protein kinase, CHD coronary heart disease, CISH cytokine-inducible SH, COPD chronic obstructive pulmonary disease, CR caloric restriction, CSF cerebrospinal fluid, GH growth hormone, H3K56ac histone 3 acetylation at the 56 lysine residue, IL interleukin, IR insulin resistance, LDL-C low-density lipoprotein cholesterol, LPS lipopolysaccharide, NAFLD nonalcoholic fatty liver disease, PBMC peripheral blood mononuclear cell, SIRT sirtuin, SOCS2 suppressor of cytokine signaling 2, STAT5b signal transducer and activator of transcription 5b, T2D type 2 diabetes, TC total cholesterol, TG triglyceride, UC ulcerative colitis