Study On the Role of Mitochondrial Dysfunction in the Pathogenesis of Metformin-associated Lactic Acidosis

On the Role of Mitochondrial Dysfunction in the Pathogenesis of Metformin-associated Lactic Acidosis

Metformin is the first line drug of choice for the treatment of type II diabetes. Lactic acidosis can develop as a side effect, especially when renal failure leads to drug accumulation. Lactic acidosis is usually attributed to an abnormal inhibition of hepatic lactate clearance.

Growing evidence suggest that metformin can dose-dependently inhibit hepatocyte mitochondrial function. Whether a similar effect occurs in extra-hepatic human tissues remains unknown.

The investigators hypothesize that mitochondrial dysfunction occurs during metformin intoxication even in tissues other than the liver, thus contributing to the development of lactic acidosis. The aim of this study is to investigate mitochondrial integrity in circulating platelets of patients with lactic acidosis due to metformin intoxication.

Study Overview

• Status: Completed
• Conditions: Lactic Acidosis; Metformin

• Study Type: Observational
• Enrollment (Actual): 10

Contacts and Locations

Study Locations

• Italy
  • MI
    • Milano, MI, Italy, 20122
      • Ospedale Maggiore Policlinico

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with lactic acidosis and metformin intoxication (as documented by drug serum measurement)

Description

Inclusion Criteria:

1. Lactic acidosis (pH < 7.35 or base deficit > 5 mmol/L and lactate > 5 mmol/L)
2. Metformin intoxication (serum drug level > 4 mcg/mL)
3. Absence of evidence of any other condition that could primarily explain the lactic acidosis

Exclusion Criteria:

1. Less than 18 years of age
2. Hemoglobin < 8 g/dL (10 g/dL if ischemic cardiac disease)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Platelet mitochondrial respiratory chain enzyme activity	Within 48 hours from admission to ICU

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Publications and helpful links

General Publications

• Protti A, Lecchi A, Fortunato F, Artoni A, Greppi N, Vecchio S, Fagiolari G, Moggio M, Comi GP, Mistraletti G, Lanticina B, Faraldi L, Gattinoni L. Metformin overdose causes platelet mitochondrial dysfunction in humans. Crit Care. 2012 Oct 3;16(5):R180. doi: 10.1186/cc11663.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: July 16, 2009
• First Submitted That Met QC Criteria: July 17, 2009
• First Posted (Estimate): July 20, 2009

Study Record Updates

• Last Update Posted (Estimate): September 27, 2013
• Last Update Submitted That Met QC Criteria: September 26, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Acid-Base Imbalance; Acidosis; Acidosis, Lactic
• Other Study ID Numbers: 2551