Clinical trial NCT01240070: Multifactorial Intervention in Type 2 Diabetes - Italy
Official title: Multicenter, Randomized Trial Designed to Evaluate the Applicability of the Guidelines of the Italian Society of Diabetology for the Prevention of Cardiovascular Diseases in Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Type 2 Diabetes
Keywords: diabetes,
cardiovascular
risk factor
cardiovascular event
intervention
Lead sponsor: University of Parma
Sponsor class: OTHER
Collaborators: name: Italian Society of Diabetology
name: AstraZeneca
name: Daiichi Sankyo
First posted: 2010-11-15
Enrollment: 1461
Sex: ALL
Minimum age (years): 50
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Despite several clinical trials have clearly demonstrated that the correction of a single cardiovascular risk factor in patients with type 2 diabetes decreases the incidence of myocardial infarction and other cardiovascular disease (CVD) events, only the Steno study has been evaluating the effect of a multifactorial intervention strategy on macrovascular complications of diabetes. For this reason, the disease management approach currently endorsed by international guidelines (i.e correction of all major CVD risk factors to target levels usually lower than lower risk populations) has not been extensively investigated in terms of prevalence of application in current clinical practice and in terms of real efficacy.

The Multifactorial INtervention in type 2 Diabetes - ITaly (MIND.IT) is a multicentric two-phase study involving 9 Diabetes Care Units throughout Italy with the overall aims of: (1) investigating the degree of application of the international guidelines for CVD prevention in type 2 diabetic patients and (2) verifying whether the application of an intensive multi-factorial intervention inspired by these guidelines is feasible and effective in decreasing the incidence of new CVD events.

Detailed description: The study is multi-centric, randomized, open label, active treatment controlled, two parallel-group, pragmatical intervention trial with 5 years of follow-up, to assess superiority of an intensive treat-to-target strategy (including lifestyle and pharmacological interventions) for correction of major cardiovascular risk factors compared to usual care in decreasing incidence of first cardiovascular events in non complicated type 2 diabetic patients at high risk, as defined by presence of 2 or more cardiovascular risk factors. All high-risk patients identified during phase 1 who accepted to participated were allocated to usual or intensive treatment based on the recruiting center. Centers were randomly assigned to treatment arm before phase 2 beginning. Investigators from Intensive Care centers received centralized training to ensure the application of the intensive care program on their patients.

HbA1c values and lipid profile are assessed in peripheral laboratories (one per each study site) with an external, centralized, quality control program and the adjustment for systematic differences among study labs.

Participating investigators are left free to decide upon patient's treatments. In intensive-care centers, investigators are provided with a multi-factorial step-wise protocol to support the application of a treat-to-target approach. Intensive care strategy includes intervention on lifestyle.

Dietary intervention goals: BMI\<25 or 5% reduction of body weight; dietary assumption of saturated fat \<10% of total caloric intake; fibers= 15-20 g/1000 Kcal. Methods defined to reach the dietary goal: A) Patients with BMI 25-30 kg/m2: reduction of caloric intake = 300-500 Cal/d; B) Patients with BMI \>30: reduction of caloric intake 500-800 Cal/d.

Physical activity intervention goal: 200-300 calories per day. Example: brisk walking for 30 min every day or biking (18-25Km/h 45-60 min). Alternatives: swimming 1h , dancing 1h, gym exercise 1h;-avoiding isometric exercise and exercise with intensity \>50-60 % of maximal oxygen consumption. Frequency: everyday or at least 3 times a week; Pharmacological intervention: Blood glucose control, multi-step intervention. In obese patients: 1) Metformin (M, 500-2500mg); 2) M+Sulphonylureas (S) or S-like drugs, increasing progressively the dose; 3) M+S+Acarbose; 4) M+S+insulin bed-time; 5) insulin basal-bolus. In normal weight patients: 1) S; 2) S+acarbose; 3) S+ bed-time insulin; 4) insulin basal bolus; Blood pressure control --\> 1) Ace-inhibitors or AT-II receptor antagonists; 2) add long acting calcium-channel blockers or beta-blockers or low dose diuretics; 3) add a third drug; lipid control: 1) diet + physical activity; 2) if LDL \> 130 mg/dL statins (with a stepwise increase of dose if necessary); if triglycerides \> 200 mg/dL fibrates; anti-platelet treatment: aspirin 100 mg/d in all patients (alternative drugs for aspirin-intolerants).

The scheduled visits were defined as follows:

* Intensive-care group: mandatory visit every three months with annual visit for MIND.IT data collection.
* Usual-care group: at least one MIND.IT visit every year + the usual organization of the center.

Eligibility criteria: Inclusion Criteria:

* Both genders
* age 50-70 years
* Type two diabetes with at least two-year history of disease and without insulin treatment in the first two years after diagnosis
* Negative medical history for documented previous cardiovascular events or macrovascular complications
* Written consent to participate
* Presence of at least 2 of the following risk factors:

  * LDL cholesterol \> 130 mg/dL (regardless of treatment)
  * Triglycerides \> 200 mg/dL
  * HDL cholesterol \< 35 (males) or 45 (females) mg/dL
  * Blood pressure \> 140/90 mmHg
  * Cigarette smoking

Exclusion Criteria:

* Age below 50 or above 70 years
* Type 1 diabetes, diagnosis before 40 years of age, known presence of auto-antibodies or insulin requirement in the first 2 years of disease.
* Chronic kidney failure (plasma creatinine \> 2 mg/dL)
* Significant liver damage (AST and/or ALT \> 2 times the upper limits of normality)
* History of previous cardiovascular events
* Active neoplasms or any concomitant disease limiting life expectancy

Primary outcomes:
measure: Cardiovascular events
timeFrame: 5 years of follow up
Secondary outcomes:
measure: cardiovascular risk factors changes
timeFrame: 2 years and 5 years of follow up
Other outcomes:
Locations:
city: Bari
country: Italy
facility: Francesco Giorgino
city: Carrara
country: Italy
facility: Maria Dolci
city: La Spezia
country: Italy
facility: Lamberto De Giorgio
city: Pavia
country: Italy
facility: Giuseppe Derosa
city: Perugia
country: Italy
facility: PierPaolo DeFeo
city: Piacenza
country: Italy
facility: Donatella Zavaroni
city: Pisa
country: Italy
facility: Roberto Miccoli
city: Roma
country: Italy
facility: Giovanni Ghirlanda
city: Torino
country: Italy
facility: Mariela Trovati
Study officials:
affiliation: University of Parma
name: Ivana Zavaroni, MD
role: STUDY_CHAIR
affiliation: Federico II University of Naples
name: Angela A Rivellese, MD
role: STUDY_DIRECTOR
affiliation: Federico II University of Naples
name: Olga Vaccaro, MD
role: STUDY_DIRECTOR
affiliation: University of Pisa
name: Roberto Miccoli, MD
role: STUDY_DIRECTOR
affiliation: University of Turin, Italy
name: Mariella Trovati, MD
role: STUDY_DIRECTOR
affiliation: University of Turin, Italy
name: Franco Cavalot, MD
role: STUDY_DIRECTOR
affiliation: INRCA of Ancona
name: Massimo Boemi, MD
role: STUDY_DIRECTOR
affiliation: University Of Perugia
name: PierPaolo DeFeo, MD
role: STUDY_DIRECTOR
References:
citation: Rivellese AA, Boemi M, Cavalot F, Costagliola L, De Feo P, Miccoli R, Patti L, Trovati M, Vaccaro O, Zavaroni I; Mind.it Study Group. Dietary habits in type II diabetes mellitus: how is adherence to dietary recommendations? Eur J Clin Nutr. 2008 May;62(5):660-4. doi: 10.1038/sj.ejcn.1602755. Epub 2007 Apr 11.
citation: Vaccaro O, Boemi M, Cavalot F, De Feo P, Miccoli R, Patti L, Rivellese AA, Trovati M, Ardigo D, Zavaroni I; MIND-IT Study Group. The clinical reality of guidelines for primary prevention of cardiovascular disease in type 2 diabetes in Italy. Atherosclerosis. 2008 Jun;198(2):396-402. doi: 10.1016/j.atherosclerosis.2007.10.026. Epub 2008 Feb 21.
citation: Vaccaro O, Franzini L, Miccoli R, Cavalot F, Ardigo D, Boemi M, De Feo P, Reboldi G, Rivellese AA, Trovati M, Zavaroni I; MIND.IT Study Group. Feasibility and effectiveness in clinical practice of a multifactorial intervention for the reduction of cardiovascular risk in patients with type 2 diabetes: the 2-year interim analysis of the MIND.IT study: a cluster randomized trial. Diabetes Care. 2013 Sep;36(9):2566-72. doi: 10.2337/dc12-1781. Epub 2013 Jul 17.
citation: Ardigo D, Vaccaro O, Cavalot F, Rivellese AA, Franzini L, Miccoli R, Patti L, Boemi M, Trovati M, Zavaroni I; MIND.IT study group. Effectiveness of treat-to-target strategy for LDL-cholesterol control in type 2 diabetes: post-hoc analysis of data from the MIND.IT study. Eur J Prev Cardiol. 2014 Apr;21(4):456-63. doi: 10.1177/2047487312467746. Epub 2012 Nov 12.