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

NCT02960711 | Completed Phase 3

• 1 other identifier: INT 85-13
• Study Type: interventional
• Target: 1,600
• Locations: 1 country
• Sites: 1

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.

Conditions

Metabolic Syndrome

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Effect of the intervention on total mortality and on the incidence of specific chronic diseases.

  8-10 years

Study Arms (4)

METFORMIN (1700MG/DAY) + LIFESTYLE

EXPERIMENTAL

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+ LIFESTYLE

PLACEBO COMPARATOR

Placebo: (two identical tablets) according to the blind assignment + participation in the life-style intervention activities

Drug: Ludipress, mg stereate, micronized hydrated silica, talcum

METFORMIN (1700 mg/day) alone

EXPERIMENTAL

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 alone

PLACEBO COMPARATOR

Placebo: (two identical tablets) according to the blind assignment

Drug: Ludipress, mg stereate, micronized hydrated silica, talcum

Interventions

Metformin Hydrochloride 850 MG Oral Tablet [Glucophage] DRUG

METFORMIN (1700 mg/day) alone; METFORMIN (1700MG/DAY) + LIFESTYLE

Ludipress, mg stereate, micronized hydrated silica, talcum DRUG

Tablet

PLACEBO alone; PLACEBO+ LIFESTYLE

Eligibility Criteria

• Age: 55 Years - 74 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (1)

Fondazione IRCCS Istituto Nazionale Tumori

Milan, 20133, Italy

Location

Related Publications (4)

• 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.

  PMID: 35333878 DERIVED

• 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.

  PMID: 30794607 DERIVED

• 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.

  PMID: 28740367 DERIVED

• 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.

  PMID: 28106245 DERIVED

MeSH Terms

Conditions

Metabolic Syndrome

Interventions

Metformin; Tablets; Dimethyl Sulfoxide

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Dosage Forms; Pharmaceutical Preparations; Sulfoxides; Sulfur Compounds

Study Officials

• Franco Berrino, MD

  Fondazione IRCCS ISTITUTO NAZIONALE TUMORI

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2016
• First Posted: November 10, 2016
• Study Start: February 1, 2014
• Primary Completion: July 1, 2019
• Study Completion: July 1, 2019
• Last Updated: September 28, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)