Phase IV Low Intervention Clinical Trial to Study Biomarkers of "inflammageing" and Senescence in Pre-diabetic Patients Treated with Metformin: A Study nested within the project “NLRP3 Inflammasome at the Crossroad of Vascular Inflammageing: A Novel Target for Senomorphic Drugs”.

Conditions

Pre-diabetic Patients

Brief summary

Circulating levels of NLRP3 inflammasome end-products (IL-1β, IL-18) at 0, 6, 12, and 18 months.

Detailed description

Circulating levels of other biomarkers for inflammation (IL6, MCP-1, TNFα, IL10), endothelial activation (sICAM, sVCAM, sE-selectin), coagulation (vWF, ADAMTS-13, D-dimer), senescence (miR-106a), oxidative stress (SOD activity, sklotho), and other parameters of endothelial dysfunction (CRP) at 0, 6, 12, and 18 months., Levels of small extracellular vesicles and large extracellular vesicles, as well as their cargo, including NLRP3 inflammasome components (pp65, NLRP3, ASC, caspase-1), IL-1β, senescence markers (p16, p21, p53, γH2AX) and senescence-related miRNAs (miR-106a) at 0, 6, 12 and 18 months., Levels of NLRP3 inflammasome components (pp65, NLRP3, ASC, caspase-1), IL-1β, senescence markers (p16, p21, p53, γH2AX), klotho, Nrf2-heme oxygenase 1 (HO-1) axis, levels of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT)) and mitochondrial function measured by metabolic flux analyzer (Seahorse) in PBMNCs at 0, 6, 12 and 18 months., Changes in BMI, glycemia, HbA1c and lipid profile (Total cholesterol, LDL, HDL and triglycerides) at 0, 6, 12 and 18 months., Changes in levels of NLRP3 inflammasome components (pp65, NLRP3, ASC, caspase-1), IL-1β, senescence markers (p16, p21, p53, γH2AX), klotho, COX-2, Nrf2-heme oxygenase 1 (HO-1) axis), levels of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT)), mitochondrial function measured by metabolic flux analyzer (Seahorse) and other cytokines (TNF-α, IL-6, MCP-1, IL10) in PBMNCs after IL-1β stimulation. Changes in levels, size and complexity and cargo components of extracellular vesicles rel, Changes in levels, size, complexity and cargo components of extracellular vesicles released by PBMNCs after IL-1β stimulation.

Related papers

No related papers found yet.

Interventions

DRUGDianben 850 mg comprimidos recubiertos con película

Eligibility

Sex/Gender

All

Age

18 Years to 64 Years

Design outcomes

Primary

Measure	Time frame
Circulating levels of NLRP3 inflammasome end-products (IL-1β, IL-18) at 0, 6, 12, and 18 months.	—

Secondary

Measure	Time frame
Circulating levels of other biomarkers for inflammation (IL6, MCP-1, TNFα, IL10), endothelial activation (sICAM, sVCAM, sE-selectin), coagulation (vWF, ADAMTS-13, D-dimer), senescence (miR-106a), oxidative stress (SOD activity, sklotho), and other parameters of endothelial dysfunction (CRP) at 0, 6, 12, and 18 months., Levels of small extracellular vesicles and large extracellular vesicles, as well as their cargo, including NLRP3 inflammasome components (pp65, NLRP3, ASC, caspase-1), IL-1β, senescence markers (p16, p21, p53, γH2AX) and senescence-related miRNAs (miR-106a) at 0, 6, 12 and 18 months., Levels of NLRP3 inflammasome components (pp65, NLRP3, ASC, caspase-1), IL-1β, senescence markers (p16, p21, p53, γH2AX), klotho, Nrf2-heme oxygenase 1 (HO-1) axis, levels of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT)) and mitochondrial function measured by metabolic flux analyzer (Seahorse) in PBMNCs at 0, 6, 12 and 18 months., Changes in BMI, glycemia, HbA1c and lipid	—

Measure

Time frame

Circulating levels of other biomarkers for inflammation (IL6, MCP-1, TNFα, IL10), endothelial activation (sICAM, sVCAM, sE-selectin), coagulation (vWF, ADAMTS-13, D-dimer), senescence (miR-106a), oxidative stress (SOD activity, sklotho), and other parameters of endothelial dysfunction (CRP) at 0, 6, 12, and 18 months., Levels of small extracellular vesicles and large extracellular vesicles, as well as their cargo, including NLRP3 inflammasome components (pp65, NLRP3, ASC, caspase-1), IL-1β, senescence markers (p16, p21, p53, γH2AX) and senescence-related miRNAs (miR-106a) at 0, 6, 12 and 18 months., Levels of NLRP3 inflammasome components (pp65, NLRP3, ASC, caspase-1), IL-1β, senescence markers (p16, p21, p53, γH2AX), klotho, Nrf2-heme oxygenase 1 (HO-1) axis, levels of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT)) and mitochondrial function measured by metabolic flux analyzer (Seahorse) in PBMNCs at 0, 6, 12 and 18 months., Changes in BMI, glycemia, HbA1c and lipid

—

Outcome results

None listed