Metformin and Longevity Genes in Prediabetes
Overview[ - collapse ][ - ]
Purpose | Pre-diabetes, a condition characterized by hyperglycaemia, is associated with increased cardiovascular risk and reduced life expectancy, as compared to the general population. AMP-activated protein kinase (AMPK) is an enzyme that plays a key role in cellular energy homeostasis and metabolism, and recently it has been demonstrated that AMPK regulates aging pathways, as well. AMPK is susceptible to modulation through pharmacologic (e.g. metformin) and non-pharmacologic (e.g. physical exercise) interventions. This clinical trial aims to describe the effects of the AMPK pathway on longevity genes and inflammation in the setting of pre-diabetes in vivo and in vitro. To this end, the investigators will compare treatment with metformin (500 mg t.i.d) for 2 months, versus placebo in pre-diabetic subjects. The investigators will assess expression of longevity genes SIRT1, p66Shc, p53 and mTOR in peripheral blood mononuclear cells (PBMCs) ex vivo. The investigators will evaluate monocyte polarization by flow cytometry, according to the expression of surface antigens (CD68, CCR2, CD163, CD206, CX3CR1) to determine the prevalence of pro- or anti-inflammatory cells. Inflammatory cytokines (TNF-alpha, MCP-1, IL-1, IL-6, IL-10, CCL12) will also be determined. In the in vitro study the investigators will evaluate the effects of AMPK activation or inhibition on longevity gene and protein expression. |
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Condition | Insulin Resistance Prediabetes Aging Inflammation |
Intervention | Drug: Metformin Drug: placebo |
Phase | Phase 4 |
Sponsor | University of Padova |
Responsible Party | University of Padova |
ClinicalTrials.gov Identifier | NCT01765946 |
First Received | January 8, 2013 |
Last Updated | March 12, 2013 |
Last verified | March 2013 |
Tracking Information[ + expand ][ + ]
First Received Date | January 8, 2013 |
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Last Updated Date | March 12, 2013 |
Start Date | June 2010 |
Estimated Primary Completion Date | March 2013 |
Current Primary Outcome Measures | Longevity gene expression [Time Frame: 2 month after treatment] [Designated as safety issue: No]Change in the expression of longevity genes Sirtuin-1, p66Shc, mTor, p53 in peripheral blood mononuclear cells (PBMC) |
Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
Brief Title | Metformin and Longevity Genes in Prediabetes |
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Official Title | Effects of Metformin on Longevity Gene Expression and Inflammation and Prediabetic Individuals. A Placebo-controlled Trial |
Brief Summary | Pre-diabetes, a condition characterized by hyperglycaemia, is associated with increased cardiovascular risk and reduced life expectancy, as compared to the general population. AMP-activated protein kinase (AMPK) is an enzyme that plays a key role in cellular energy homeostasis and metabolism, and recently it has been demonstrated that AMPK regulates aging pathways, as well. AMPK is susceptible to modulation through pharmacologic (e.g. metformin) and non-pharmacologic (e.g. physical exercise) interventions. This clinical trial aims to describe the effects of the AMPK pathway on longevity genes and inflammation in the setting of pre-diabetes in vivo and in vitro. To this end, the investigators will compare treatment with metformin (500 mg t.i.d) for 2 months, versus placebo in pre-diabetic subjects. The investigators will assess expression of longevity genes SIRT1, p66Shc, p53 and mTOR in peripheral blood mononuclear cells (PBMCs) ex vivo. The investigators will evaluate monocyte polarization by flow cytometry, according to the expression of surface antigens (CD68, CCR2, CD163, CD206, CX3CR1) to determine the prevalence of pro- or anti-inflammatory cells. Inflammatory cytokines (TNF-alpha, MCP-1, IL-1, IL-6, IL-10, CCL12) will also be determined. In the in vitro study the investigators will evaluate the effects of AMPK activation or inhibition on longevity gene and protein expression. |
Detailed Description | Not Provided |
Study Type | Interventional |
Study Phase | Phase 4 |
Study Design | Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment |
Condition |
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Intervention | Drug: Metformin Metformin tablets 500 mg tris in die (tid) Other Names: GlucophageDrug: placebo |
Study Arm (s) |
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Recruitment Information[ + expand ][ + ]
Recruitment Status | Completed |
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Estimated Enrollment | 38 |
Estimated Completion Date | March 2013 |
Estimated Primary Completion Date | March 2013 |
Eligibility Criteria | Inclusion Criteria: - Pre-diabetes, defined as IFG (fasting glucose between 100 and 125 mg/dl) or IGT (2h post-oral glucose load (75g) between 140 and 199 mg/dl); - Age 40-75 years; - Both genders. Exclusion Criteria: - Type 1 or 2 diabetes mellitus; - Pregnancy, lactation; - Acute, chronic or inflammatory diseases; - Neoplasms; - Immunological diseases, organ transplantation, steroid therapy; - Uncontrolled arterial hypertension (systolic pressure > 180 mmHg or diastolic > 120 mmHg); - Recent(within 3 months) surgical intervention or cardiovascular accidents; - Known allergy to metformin. |
Gender | Both |
Ages | 40 Years |
Accepts Healthy Volunteers | No |
Contacts | Not Provided |
Location Countries | Italy |
Administrative Information[ + expand ][ + ]
NCT Number | NCT01765946 |
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Other Study ID Numbers | MetAge |
Has Data Monitoring Committee | No |
Information Provided By | University of Padova |
Study Sponsor | University of Padova |
Collaborators | Not Provided |
Investigators | Principal Investigator: Angelo Avogaro, M.D. Ph.D. University of Padova |
Verification Date | March 2013 |
Locations[ + expand ][ + ]
University Hospital Diabetes Outpatient Clinic | Padova, Italy, 35128 |
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