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Metformin and Longevity Genes in Prediabetes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Angelo Avogaro, University of Padova
ClinicalTrials.gov Identifier:
NCT01765946
First received: January 8, 2013
Last updated: March 12, 2013
Last verified: March 2013
History of Changes
  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.


Condition Intervention Phase
Insulin Resistance
Prediabetes
Aging
Inflammation
 Drug: Metformin
Drug: placebo
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Effects of Metformin on Longevity Gene Expression and Inflammation and Prediabetic Individuals. A Placebo-controlled Trial

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Padova:

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)


Secondary Outcome Measures:
  • Insulin sensitivity [ Time Frame: 2 months after treatment ] [ Designated as safety issue: No ]
    A dynamic measure of insulin sensitivity (Si) from the frequently sampled OGTT

  • Monocyte polarization status [ Time Frame: 2 months after treatment ] [ Designated as safety issue: No ]
    Polarization of circulating monocytes in M1 (CD68+CCR2+) and M2 (CX3CR1+CD163+/CD206+)


Enrollment: 38
Study Start Date: June 2010
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Metformin
Metformin tablets 500 mg tid for 2 months
 Drug: Metformin
Metformin tablets 500 mg tris in die (tid)
Other Name: Glucophage
Placebo Comparator: Placebo
Placebo tables tid for 2 months
 Drug: placebo

  Eligibility

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01765946

Locations
Italy
University Hospital Diabetes Outpatient Clinic
Padova, Italy, 35128
Sponsors and Collaborators
University of Padova
Investigators
Principal Investigator: Angelo Avogaro, M.D. Ph.D. University of Padova
  More Information

No publications provided

Responsible Party: Angelo Avogaro, Full professor of Endocrinology and Metabolism, University of Padova
ClinicalTrials.gov Identifier: NCT01765946     History of Changes
Other Study ID Numbers: MetAge
Study First Received: January 8, 2013
Last Updated: March 12, 2013
Health Authority: Italy: Ministry of Health

Keywords provided by University of Padova:
Insulin resistance
Prediabetes
Longevity genes
Inflammation
Metformin

Additional relevant MeSH terms:
Inflammation
Insulin Resistance
Glucose Intolerance
Prediabetic State
Pathologic Processes
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
 Hyperglycemia
Diabetes Mellitus
Endocrine System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 16, 2013