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Metformin and Longevity Genes in Prediabetes

Primary Purpose

Insulin Resistance, Prediabetes, Aging

Status

Completed

Phase

Phase 4

Locations

Italy

Study Type

Interventional

Intervention

Metformin

placebo

About this trial

This is an interventional treatment trial for Insulin Resistance focused on measuring Insulin resistance, Prediabetes, Longevity genes, Inflammation, Metformin

Eligibility Criteria

40 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University Hospital Diabetes Outpatient Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Metformin

Placebo

Arm Description

Metformin tablets 500 mg tid for 2 months

Placebo tables tid for 2 months

Outcomes

Primary Outcome Measures

Longevity gene expression

Change in the expression of longevity genes Sirtuin-1, p66Shc, mTor, p53 in peripheral blood mononuclear cells (PBMC)

Secondary Outcome Measures

Insulin sensitivity

A dynamic measure of insulin sensitivity (Si) from the frequently sampled OGTT

Monocyte polarization status

Polarization of circulating monocytes in M1 (CD68+CCR2+) and M2 (CX3CR1+CD163+/CD206+)

Full Information

NCT ID

NCT01765946

First Posted

January 8, 2013

Last Updated

March 12, 2013

Sponsor

University of Padova

1. Study Identification

Unique Protocol Identification Number

NCT01765946

Brief Title

Metformin and Longevity Genes in Prediabetes

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2013

Overall Recruitment Status

Completed

Study Start Date

June 2010 (undefined)

Primary Completion Date

March 2013 (Actual)

Study Completion Date

March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Padova

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Insulin Resistance, Prediabetes, Aging, Inflammation

Keywords

Insulin resistance, Prediabetes, Longevity genes, Inflammation, Metformin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

38 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Metformin

Arm Type

Experimental

Arm Description

Metformin tablets 500 mg tid for 2 months

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo tables tid for 2 months

Intervention Type

Drug

Intervention Name(s)

Metformin

Other Intervention Name(s)

Glucophage

Intervention Description

Metformin tablets 500 mg tris in die (tid)

Intervention Type

Drug

Intervention Name(s)

placebo

Primary Outcome Measure Information:

Title

Longevity gene expression

Description

Change in the expression of longevity genes Sirtuin-1, p66Shc, mTor, p53 in peripheral blood mononuclear cells (PBMC)

Time Frame

2 month after treatment

Secondary Outcome Measure Information:

Title

Insulin sensitivity

Description

A dynamic measure of insulin sensitivity (Si) from the frequently sampled OGTT

Time Frame

2 months after treatment

Title

Monocyte polarization status

Description

Polarization of circulating monocytes in M1 (CD68+CCR2+) and M2 (CX3CR1+CD163+/CD206+)

Time Frame

2 months after treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Angelo Avogaro, M.D. Ph.D.

Organizational Affiliation

University of Padova

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospital Diabetes Outpatient Clinic

City

Padova

ZIP/Postal Code

35128

Country

Italy

12. IPD Sharing Statement

Citations:

PubMed Identifier

25921843

Citation

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.

Results Reference

derived

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Metformin and Longevity Genes in Prediabetes

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