Metformin and Longevity Genes in Prediabetes

Aging Clinical Trial

Official title:

Effects of Metformin on Longevity Gene Expression and Inflammation and Prediabetic Individuals. A Placebo-controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01765946
• Other study ID #: MetAge
• Status: Completed
• Phase: Phase 4
• First received: January 8, 2013
• Last updated: March 12, 2013
• Start date: June 2010
• Est. completion date: March 2013

Study information

• Verified date: March 2013
• Source: University of Padova
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Aging
• Glucose Intolerance
• Inflammation
• Insulin Resistance
• Prediabetes
• Prediabetic State

Intervention

Drug:
• Metformin
Metformin tablets 500 mg tris in die (tid)
• placebo

Locations

Country	Name	City	State
Italy	University Hospital Diabetes Outpatient Clinic	Padova

Sponsors (1)

Lead Sponsor	Collaborator
University of Padova

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Longevity gene expression	Change in the expression of longevity genes Sirtuin-1, p66Shc, mTor, p53 in peripheral blood mononuclear cells (PBMC)	2 month after treatment	No
Secondary	Insulin sensitivity	A dynamic measure of insulin sensitivity (Si) from the frequently sampled OGTT	2 months after treatment	No
Secondary	Monocyte polarization status	Polarization of circulating monocytes in M1 (CD68+CCR2+) and M2 (CX3CR1+CD163+/CD206+)	2 months after treatment	No