Metformin and Longevity Genes in Prediabetes

NCT ID: NCT01765946

Last Updated: 2013-03-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2013-03-31

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.

Conditions

Insulin Resistance; Prediabetes; Aging; Inflammation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Metformin

Metformin tablets 500 mg tid for 2 months

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

Metformin tablets 500 mg tris in die (tid)

Placebo

Placebo tables tid for 2 months

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Interventions

Metformin

Metformin tablets 500 mg tris in die (tid)

Intervention Type: DRUG

placebo

Intervention Type: DRUG

Other Intervention Names

Glucophage

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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Padova

OTHER

Sponsor Role: lead

Responsible Party

Angelo Avogaro

Full professor of Endocrinology and Metabolism

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Angelo Avogaro, M.D. Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Padova

Locations

University Hospital Diabetes Outpatient Clinic

Padua, Italy, Italy

Countries

Italy

References

de Kreutzenberg SV, Ceolotto G, Cattelan A, Pagnin E, Mazzucato M, Garagnani P, Borelli V, Bacalini MG, Franceschi C, Fadini GP, Avogaro A. Metformin improves putative longevity effectors in peripheral mononuclear cells from subjects with prediabetes. A randomized controlled trial. Nutr Metab Cardiovasc Dis. 2015 Jul;25(7):686-93. doi: 10.1016/j.numecd.2015.03.007. Epub 2015 Mar 24.

Reference Type: DERIVED

PMID: 25921843 (View on PubMed)

Other Identifiers

MetAge

Identifier Type: -

Identifier Source: org_study_id