Metformin and Dietary Restriction to Prevent Age-related Morbid Events in People With Metabolic Syndrome (MeMeMe)

Randomized Controlled Trial of Metformin and Dietary Restriction to Prevent Age-related Morbid Events in People With Metabolic Syndrome

Phase III randomized controlled trial on men and women with Metabolic syndrome (MetS) to test the hypothesis that comprehensive life-style changes and/or metformin treatment prevent age-related chronic non-communicable diseases (ArCD).

The aim of the present study is to evaluate the effect of a comprehensive life-style intervention (including moderate physical activity and Mediterranean/macrobiotic diet with moderate calorie and protein restriction), and of treatment with Metformin (a calorie restriction mimetic drug) for the prevention of ArCD.

Study Overview

• Status: Completed
• Conditions: Metabolic Syndrome
• Intervention / Treatment: Drug: Metformin Hydrochloride 850 MG Oral Tablet [Glucophage]; Drug: Ludipress, mg stereate, micronized hydrated silica, talcum

Detailed Description

Phase III randomized controlled trial on men and women with MetS to test the hypothesis that comprehensive life-style changes and/or metformin treatment prevent ArCD.

Design:

2x2 factorial: 2,000 volunteers will be randomized in four equal groups of 500 each, and allocated to the following treatments: METFORMIN (1700MG/DAY) + ACTIVE LIFESTYLE INTERVENTION PLACEBO + ACTIVE LIFESTYLE INTERVENTION METFORMIN (1700 mg/day) alone PLACEBO alone The metformin /placebo component of the study will be double blind.

• Study Type: Interventional
• Enrollment (Actual): 1600
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale Tumori

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 55-74, waist circumference equal or greater than 85 cm for women and 100 cm for men, plus at least two other factors among those defining the MetS

Exclusion Criteria:

• Diagnosed diabetes (or baseline fasting glycemia above 7mmol/L at baseline examination)
• Cancer (except skin carcinoma) diagnosed in the last 5 years, or under treatment
• Excessive frailty: in absence of agreed-upon measurements parameters and cutoff points, the investigator will exclude subjects under the lower 5th percentile of the muscular mass distribution estimated by impedance in previous studies

• Conditions that contraindicate the use of MET because might favour lactic acidosis:

  • Renal, cardiac, hepatic, or respiratory insufficiency
  • Serum creatinine <124μmol/L, or proteinuria at baseline examination
  • Current treatment with K-sparing diuretics, or with proton pump inhibitors
  • Excessive alcohol consumption
• Distressing side effects of MET treatment. Nausea and diarrhoea typically occur in about one third of patients receiving MET for the first time at full dose. To avoid dropouts for gastrointestinal discomfort we will treat all volunteers with half the planned dose for one month in order to exclude intolerant subjects before randomization. Participants randomized in the intervention group will continue to take half a dose for one month and then shift to the full dose.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: METFORMIN (1700MG/DAY) + LIFESTYLE; METFORMIN: 2 tablets per day, one at breakfast (or lunch) and one at dinner, of either metformin (two 850 mg tablets/day) + participation in the life-style intervention activities	Drug: Metformin Hydrochloride 850 MG Oral Tablet [Glucophage]
Placebo Comparator: PLACEBO+ LIFESTYLE; Placebo: (two identical tablets) according to the blind assignment + participation in the life-style intervention activities	Drug: Ludipress, mg stereate, micronized hydrated silica, talcum; Tablet
Experimental: METFORMIN (1700 mg/day) alone; METFORMIN: 2 tablets per day, one at breakfast (or lunch) and one at dinner, of either metformin (two 850 mg tablets/day)	Drug: Metformin Hydrochloride 850 MG Oral Tablet [Glucophage]
Placebo Comparator: PLACEBO alone; Placebo: (two identical tablets) according to the blind assignment	Drug: Ludipress, mg stereate, micronized hydrated silica, talcum; Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total incidence of age related chronic diseases	We will retrieve records for all Age related chronic diseases but we will first concentrate the analysis on cancer, coronary heart disease, stroke, and diabetes	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of the intervention on total mortality and on the incidence of specific chronic diseases.	The measure is a composite outcome measure consisting of multiple measures (results to be reported as a single value for each Arm/Group). The outcome measure describes multiple assessments with potentially different Units of Measure as indicated: Waist circumference: cm Glycemia: mg/dL Blood pressure: mmHg Total cholesterol, HDL cholesterol: mg/dL Triglycerides: mg/dL	8-10 years

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Investigators: Principal Investigator: Franco Berrino, MD, Fondazione IRCCS Istituto Nazionale Tumori

Publications and helpful links

General Publications

• Baldassari I, Oliverio A, Krogh V, Bruno E, Gargano G, Cortellini M, Casagrande A, Di Mauro MG, Venturelli E, Del Sette Cerulli D, Manuela B, Berrino F, Pasanisi P. Recruitment in randomized clinical trials: The MeMeMe experience. PLoS One. 2022 Mar 25;17(3):e0265495. doi: 10.1371/journal.pone.0265495. eCollection 2022.
• Cortellini M, Casagrande A, Fornaciari G, Del Sette D, Gargano G, Di Mauro MG, Saibene G, Bruno E, Villarini A, Venturelli E, Berrino F, Baldassari I, Oliverio A, Pasanisi P. A management system for randomized clinical trials: A novel way to supply medication. PLoS One. 2019 Feb 22;14(2):e0212475. doi: 10.1371/journal.pone.0212475. eCollection 2019.
• Cortellini M, Berrino F, Pasanisi P. "Open mesh" or "strictly selected population" recruitment? The experience of the randomized controlled MeMeMe trial. Patient Prefer Adherence. 2017 Jul 6;11:1127-1132. doi: 10.2147/PPA.S135412. eCollection 2017.
• Pasanisi P, Gargano G, Gaetana Di Mauro M, Cortellini M, Casagrande A, Villarini A, Bruno E, Roveda E, Saibene G, Venturelli E, Berrino F. A randomized controlled trial of Mediterranean diet and metformin to prevent age-related diseases in people with metabolic syndrome. Tumori. 2018 Mar-Apr;104(2):137-142. doi: 10.5301/tj.5000599. Epub 2018 May 8.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): July 1, 2019
• Study Completion (Actual): July 1, 2019

Study Registration Dates

• First Submitted: October 21, 2016
• First Submitted That Met QC Criteria: November 7, 2016
• First Posted (Estimate): November 10, 2016

Study Record Updates

• Last Update Posted (Actual): September 28, 2021
• Last Update Submitted That Met QC Criteria: September 27, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Insulin Resistance; Hyperinsulinism; Syndrome; Metabolic Syndrome; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: INT 85-13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO