The Sapienza University Mortality and Morbidity Events Rate (SUMMER) Study in Diabetes

Type 2 Diabetes Mellitus Clinical Trial

— SUMMER  

Official title:

The Sapienza University Mortality and Morbidity Events Rate (SUMMER) Study in Diabetes: Identification of New Molecular Promoters of Mortality and Morbidity in Patients With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02311244
• Other study ID #: URomLS-01-2014
• Status: Completed
• Start date: January 2014
• Est. completion date: December 2022

Study information

• Verified date: May 2023
• Source: University of Roma La Sapienza
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This observational study is aimed at identifying new molecular promoters of mortality (and morbidity) in patients with type 2 diabetes mellitus (T2DM).

Description:

Background Mortality rate of diabetic patients is about twice as much that of non-diabetic individuals of similar age; this makes diabetes a leading risk factor for mortality, especially of cardiovascular origin, which accounts for 2.9 million global events yearly. Such scenario is expected to further deteriorate, given that the prevalence of type 2 diabetes mellitus (T2DM), by far the most common form of diabetes comprising more than 90% of all diabetic individuals, is increasing worldwide. Predicting such devastating event is, therefore, urgently needed in order to target aggressive prevention strategies in high risk T2DM patients.

Aims This observational study is aimed at identifying new molecular promoters of all-cause mortality in patients with T2DM.

Secondary endpoints are to identify in these individuals molecular markers of

• cardiovascular mortality;

• myocardial infarction;

• stroke;

• dialysis.

Other pre-specified endpoints are to assess in these subjects:

• LADA;

• severe hypoglycemic episodes;

• revascularization procedures;

• hospitalization for heart failure;

• other co-morbidities (cancer - at follow-up only, liver disease, chronic obstructive pulmonary disease, autoimmune and endocrine disorders, other - non-diabetic - renal diseases, fractures, cognitive impairment).

Patients A total of 5,000 patients with T2DM of both sexes will be recruited. Measures The following parameters will be recorded as exposure variables at baseline.

• Age, BMI, waist circumference, systolic and diastolic pressure;

• Lifestyle habits, including diet, physical activity (both by validated questionnaires) and smoking.

• Menopausal state (for women).

• Family history of diabetes (3 consecutive generations).

• Family history of cardiovascular disease (first degree relatives).

• Diabetes duration.

• Severe (requiring assistance) hypoglycemic episodes (per year).

• Myocardial infarction, stroke, ulcer/gangrene/amputation, coronary and peripheral revascularization, hospitalization for heart failure, dialysis (at follow-up only).

• Glucose, HbA1c, creatinine, uric acid, total and HDL cholesterol, triglycerides, high sensitive C reactive protein, testosterone, Vitamin D, uric acid levels, white blood cells counting, urinary albumin creatinine ratio (ACR)

• Current glucose-, lipid-, blood pressure-lowering and anti-platelet or anti-coagulant treatment.

• Other relevant treatments (steroids, NSAIDs, immunomodulators, androgens, estrogens, anti-fracturative therapy).

• Main co-morbidities (cancer, chronic liver disease, chronic obstructive pulmonary disease, autoimmune and endocrine disorders, other - non-diabetic - renal diseases, fractures, cognitive impairment).

The following parameters will be assessed at baseline only:

• GADAs (by a radiobinding assay using in vitro translated [35S] methionine-labelled GAD65) and IA-2 antibodies (by radioimmunoprecipitation assays) to identify subjects with LADA.

• Genomic (common and rare variants in genes of interest according to a pathway-centric approach by means of Affymetrix platforms), transcriptomic (differential levels of mRNA by GeneChip Human Gene 1.0 ST Array from Affymetrix) and metabolomic by a combination of ultra-pressure liquid chromatography and gas chromatography coupled to mass spectrometry) analysis.

Measurements of testosterone, Vitamin D, GADAs and IA-2 antibodies as well as gnomic, transcriptomic and metabolomic analysis will be centralized.

Time schedule Recruitment of patients will last approximately 3 years. The enrolled patients will be followed for at least 5 years with yearly visits and telephone calls or consultation of death records in case of drop-out for unknown reasons.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5139
• Est. completion date: December 2022
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

Type 2 diabetes mellitus

Exclusion Criteria:

• Severe psychiatric illnesses

• End-stage renal disease and dialysis

• Cirrhosis

• Any active cancer

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Locations

Country	Name	City	State
Italy	University of Roma La Sapienza	Rome	RM

Sponsors (6)

Lead Sponsor	Collaborator
University of Roma La Sapienza	Azienda Ospedaliera San Camillo Forlanini, Campus Bio-Medico University, Casa Sollievo della Sofferenza IRCCS, Ospedale Sandro Pertini, Roma, University of Cagliari

Country where clinical trial is conducted

Italy, 

References & Publications (6)

De Cosmo S, Copetti M, Lamacchia O, Fontana A, Massa M, Morini E, Pacilli A, Fariello S, Palena A, Rauseo A, Viti R, Di Paola R, Menzaghi C, Cignarelli M, Pellegrini F, Trischitta V. Development and validation of a predicting model of all-cause mortality in patients with type 2 diabetes. Diabetes Care. 2013 Sep;36(9):2830-5. doi: 10.2337/dc12-1906. Epub 2013 May 1. — View Citation

Hong Kong Diabetes Registry; Yang X, So WY, Tong PC, Ma RC, Kong AP, Lam CW, Ho CS, Cockram CS, Ko GT, Chow CC, Wong VC, Chan JC. Development and validation of an all-cause mortality risk score in type 2 diabetes. Arch Intern Med. 2008 Mar 10;168(5):451-7. doi: 10.1001/archinte.168.5.451. — View Citation

McEwen LN, Karter AJ, Waitzfelder BE, Crosson JC, Marrero DG, Mangione CM, Herman WH. Predictors of mortality over 8 years in type 2 diabetic patients: Translating Research Into Action for Diabetes (TRIAD). Diabetes Care. 2012 Jun;35(6):1301-9. doi: 10.2337/dc11-2281. Epub 2012 Mar 19. — View Citation

Rao Kondapally Seshasai S, Kaptoge S, Thompson A, Di Angelantonio E, Gao P, Sarwar N, Whincup PH, Mukamal KJ, Gillum RF, Holme I, Njolstad I, Fletcher A, Nilsson P, Lewington S, Collins R, Gudnason V, Thompson SG, Sattar N, Selvin E, Hu FB, Danesh J; Emerging Risk Factors Collaboration. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med. 2011 Mar 3;364(9):829-841. doi: 10.1056/NEJMoa1008862. Erratum In: N Engl J Med. 2011 Mar 31;364(13):1281. — View Citation

Roglic G, Unwin N, Bennett PH, Mathers C, Tuomilehto J, Nag S, Connolly V, King H. The burden of mortality attributable to diabetes: realistic estimates for the year 2000. Diabetes Care. 2005 Sep;28(9):2130-5. doi: 10.2337/diacare.28.9.2130. — View Citation

Wells BJ, Jain A, Arrigain S, Yu C, Rosenkrans WA Jr, Kattan MW. Predicting 6-year mortality risk in patients with type 2 diabetes. Diabetes Care. 2008 Dec;31(12):2301-6. doi: 10.2337/dc08-1047. Epub 2008 Sep 22. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of all-cause deaths	Number of participants who die for all causes and time of occurrence of such events	5 years
Secondary	Number of cardiovascular deaths	Number of participants who die for cardiovascular causes and time of occurrence of such events	5 years
Secondary	Number of subjects with myocardial infarction	Number of participants who develop myocardial infarction and time of occurrence of such events	5 years
Secondary	Number of subjects with stroke	Number of participants who develop stroke and time of occurrence of such events	5 years
Secondary	Number of subjects entering dialysis	Number of participants who enter dialysis and time of occurrence of such events	5 years

External Links

•   Study webpage