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

Phase 3

Completed

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

• Registration Number: NCT02960711
• Lead Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Brief Summary

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.

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 Timeline

• Study Start: 2014-02
• Study First Submitted: 2016-10-21
• Study First Submitted QC: 2016-11-07
• Study First Posted: 2016-11-10
• Primary Completion: 2019-07
• Study Completion: 2019-07
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-27
• Last Update Posted: 2021-09-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1600

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Total incidence of age related chronic diseases	5 years	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

Secondary Outcome Measures

Name	Time	Method
Effect of the intervention on total mortality and on the incidence of specific chronic diseases.	8-10 years	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

Trial Locations

Locations (1)

Fondazione IRCCS Istituto Nazionale Tumori; 🇮🇹 Milan, Italy