Clinical trial NCT02960711: Metformin and Dietary Restriction to Prevent Age-related Morbid Events in People With Metabolic Syndrome
Official title: Randomized Controlled Trial of Metformin and Dietary Restriction to Prevent Age-related Morbid Events in People With Metabolic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metabolic Syndrome
Lead sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Sponsor class: OTHER
First posted: 2016-11-10
Enrollment: 1600
Sex: ALL
Minimum age (years): 55
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Total incidence of age related chronic diseases
timeFrame: 5 years
Secondary outcomes:
measure: Effect of the intervention on total mortality and on the incidence of specific chronic diseases.
timeFrame: 8-10 years
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale Tumori
Study officials:
affiliation: Fondazione IRCCS ISTITUTO NAZIONALE TUMORI
name: Franco Berrino, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.