NCT01765946

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
38

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started Jun 2010

Typical duration for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2010

Completed
2.6 years until next milestone

First Submitted

Initial submission to the registry

January 8, 2013

Completed
3 days until next milestone

First Posted

Study publicly available on registry

January 11, 2013

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2013

Completed
Last Updated

March 13, 2013

Status Verified

March 1, 2013

Enrollment Period

2.8 years

First QC Date

January 8, 2013

Last Update Submit

March 12, 2013

Conditions

Insulin ResistancePrediabetesAgingInflammation

Keywords

Insulin resistancePrediabetesLongevity genesInflammationMetformin

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (2)

  • Insulin sensitivity

    2 months after treatment

  • Monocyte polarization status

    2 months after treatment

Study Arms (2)

Metformin

EXPERIMENTAL

Metformin tablets 500 mg tid for 2 months

Drug: Metformin

Placebo

PLACEBO COMPARATOR

Placebo tables tid for 2 months

Drug: placebo

Interventions

MetforminDRUG

Metformin tablets 500 mg tris in die (tid)

Also known as: Glucophage
Metformin
placeboDRUG
Placebo

Eligibility Criteria

Age40 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hospital Diabetes Outpatient Clinic

Padua, Italy, 35128, Italy

Location

Related Publications (1)

  • 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.

    PMID: 25921843DERIVED

MeSH Terms

Conditions

Insulin ResistancePrediabetic StateInflammation

Interventions

Metformin

Condition Hierarchy (Ancestors)

HyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesDiabetes MellitusEndocrine System DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

BiguanidesGuanidinesAmidinesOrganic Chemicals

Study Officials

  • Angelo Avogaro, M.D. Ph.D.

    University of Padova

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Full professor of Endocrinology and Metabolism

Study Record Dates

First Submitted

January 8, 2013

First Posted

January 11, 2013

Study Start

June 1, 2010

Primary Completion

March 1, 2013

Study Completion

March 1, 2013

Last Updated

March 13, 2013

Record last verified: 2013-03

Locations

IT(1)