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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT01898572
Other study ID # PI11-DIABIMCAP
Secondary ID PI11/01723
Status Active, not recruiting
Phase N/A
First received July 10, 2013
Last updated June 24, 2014
Start date January 2012
Est. completion date June 2015

Study information

Verified date June 2014
Source Hospital Clinic of Barcelona
Contact n/a
Is FDA regulated No
Health authority Spain: Ethics Committee
Study type Observational

Clinical Trial Summary

It has been hypothesized, based on recent trials, that only early intervention can reduce cardiovascular morbidity and mortality in individuals with type 2 diabetes (T2DM). This finding may imply that atherosclerosis at diabetes diagnosed, is either negligible, or at early, or non-advanced, still modifiable disease stage. However, sparse information is available regarding atherosclerosis prevalence and its characteristics at diabetes presentation. Furthermore, although cardiovascular disease (CVD) prevention is the major goal of treatment in T2DM, risk assessment tools, mostly based on traditional CV risk factors, lack of adequate specificity to identify individuals at higher risk. Therefore, non-invasive tests, such as carotid ultrasound, have been recommended to better define CV risk in several groups of individuals, including those with intermediate risk or with T2DM.

This clinical study aims to improve the investigators knowledge on cardiovascular disease (CVD) in subjects with newly diagnosed T2DM (NEWDM). The investigators hypothesis is that carotid ultrasound (carotid intimae media thickness [CIMT] and carotid plaque [CP]) will show a worse subclinical/preclinical CVD stage in NEWDM compared with non-diabetic (CONTROL) individuals. Moreover, carotid ultrasound will also identify T2DM individuals at a higher risk in whom intervention should be more intensive.

Because individuals with T2DM have a higher prevalence of several CV risk factors, NEWDM will be matched with CONTROL individuals, not only for age and sex (the main determinants of atherosclerosis), but also for known, treated hypertension and dyslipidemia, and smoking habit.

The investigators will study NEWDM and CONTROL individuals without clinical CVD. This is a cross-sectional and longitudinal (18 months of follow-up) case-control study. The main study variables will be carotid ultrasound derived variables. The main aims of the study are: 1) to investigate CIMT and CP prevalence differences between NEWDM and CONTROL subjects; 2) to characterize the subset of NEWDM subjects with a higher CIMT (≥ mean+1SD o ≥ P75th) or CP presence; and 3) to early characterize individuals in whom subclinical CVD worsens (CIMT progression ≥ mean + 1SD o ≥ P75th) even after standard (according to clinical guidelines) diabetes treatment.


Description:

Hypothesis:

In a Mediterranean population, the investigators hypothesized that the CIMT and the presence of carotid plaque (CP):

1. Are higher in patients with newly diagnosed T2DM than in a control population before and after adjusting for cardiovascular risk factors,

2. Can identify subjects with T2DM with increased cardiovascular risk at the beginning of the disease, and,

3. Can identify subjects in whom subclinical cardiovascular disease progresses despite treatment of T2DM according to clinical practice.

Aims:

Primary objectives:

1. To investigate differences in CIMT and the presence of CP in subjects with NEWDM and a control population. Cross-sectional study.

2. To identify and characterize the subset of NEWDM subjects presenting an increased CIMT (greater than the mean + 1SD or ≥ P75th) or carotid plaque presence. Cross-sectional study

3. To early characterize individuals in whom subclinical CVD worsens (CIMT progression ≥ mean + 1SD o ≥ P75th) even after multifactorial treatment of diabetes according to guidelines. Longitudinal study design with repeated measures.

Secondary objectives:

1. To study the main determinants of CIMT and the CP presence in NEWDM subjects and a control population. In addition to the cardiovascular risk factors will be studied:

1. association with Mediterranean diet biomarkers (serum and urine) and diet adherence (semiquantitative food frequency questionnaire)

2. genetic determinants of CVD

2. To investigate the main determinants of progression of CIMT in subjects treated according to clinical practice guidelines

3. To investigate the association of baseline CIMT, its progression, and the presence of CP with clinical scores used to estimate cardiovascular risk. These scores are: REGICOR (Registre Gironí del Cor: the Gerona Heart Register), a calibrated Framingham Score for a Mediterranean population, low risk SCORE (Systematic Coronary Risk Evaluation), and the UKPDS (United Kingdom Prospective Diabetes Study) score (specific for T2DM).

4. To identify carotid plaque biomarkers by a metabolomic approach


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 200
Est. completion date June 2015
Est. primary completion date April 2015
Accepts healthy volunteers No
Gender Both
Age group 40 Years to 74 Years
Eligibility Inclusion Criteria:

- Adult men and women older than 40 years and less than 75 years.

- Newly Diagnosed T2DM (NEWDM). NEWDM is a subject without previous history of diabetes who has laboratory evidence consistent with diabetes (American Diabetes Association) within the last year.

Exclusion criteria:

- Previous cardiovascular events such as, but not limited to, myocardial infarction, acute coronary syndrome or chronic stroke, peripheral arterial disease, or revascularization surgery in any territory.

- Congestive heart failure (class III-IV).

- Cancer of any kind (except basal cell or for cervical carcinoma insitu) unless disease free is documented in the past five years.

- Anemia or known coagulopathy.

- Serum creatinine greater than 1.5 mg / dl or MDRD (Modification of Diet in Renal Disease) equation <50.

- Any organ transplant (except cornea)

- Known HIV-positive, active tuberculosis, malaria, chronic viral hepatitis B or C, cirrhosis of any aetiology.

- Pregnant or gestational idea in the next 2-3 years to inclusion.

- History of alcohol dependence (or abusive consumption) or other drugs in the past five years.

- Psychiatric illness that would entail adherence problems.

- Participation in a clinical trial protocol or investigational drugs.

- Debilitating chronic illness or short life expectancy to prevent adherence or therapeutic intensification is not the goal of managing your diabetes.

- ECG signs of ischemic heart disease.

- Diabetes type 1 or anti-GAD antibody positive.

Control population will be excluded based on the same criteria.

Study Design

Observational Model: Case Control, Time Perspective: Prospective


Related Conditions & MeSH terms


Intervention

Other:
Standard care
Newly T2DM and control individuals will be controlled by their family care physician following standard (clinical guidelines) care.

Locations

Country Name City State
Spain Hospital Clinic of Barcelona Barcelona Cataluña

Sponsors (2)

Lead Sponsor Collaborator
Hospital Clinic of Barcelona Consorci d'Atenció Primària de Salut de l'Eixample

Country where clinical trial is conducted

Spain, 

References & Publications (10)

Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008 Jun 12;358(24):2545-59. doi: 10.1056/NEJMoa0802743. Epub 2008 Jun 6. — View Citation

ADVANCE Collaborative Group, Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Hamet P, Harrap S, Heller S, Liu L, Mancia G, Mogensen CE, Pan C, Poulter N, Rodgers A, Williams B, Bompoint S, de Galan BE, Joshi R, Travert F. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008 Jun 12;358(24):2560-72. doi: 10.1056/NEJMoa0802987. Epub 2008 Jun 6. — View Citation

Emerging Risk Factors Collaboration, Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA, Selvin E, Stampfer M, Stehouwer CD, Lewington S, Pennells L, Thompson A, Sattar N, White IR, Ray KK, Danesh J. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010 Jun 26;375(9733):2215-22. doi: 10.1016/S0140-6736(10)60484-9. Erratum in: Lancet. 2010 Sep 18;376(9745):958. Hillage, H L [corrected to Hillege, H L]. — View Citation

Greenland P, Alpert JS, Beller GA, Benjamin EJ, Budoff MJ, Fayad ZA, Foster E, Hlatky MA, Hodgson JM, Kushner FG, Lauer MS, Shaw LJ, Smith SC Jr, Taylor AJ, Weintraub WS, Wenger NK, Jacobs AK, Smith SC Jr, Anderson JL, Albert N, Buller CE, Creager MA, Ettinger SM, Guyton RA, Halperin JL, Hochman JS, Kushner FG, Nishimura R, Ohman EM, Page RL, Stevenson WG, Tarkington LG, Yancy CW; American College of Cardiology Foundation; American Heart Association. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2010 Dec 14;56(25):e50-103. doi: 10.1016/j.jacc.2010.09.001. — View Citation

Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008 Oct 9;359(15):1577-89. doi: 10.1056/NEJMoa0806470. Epub 2008 Sep 10. — View Citation

Nambi V, Chambless L, Folsom AR, He M, Hu Y, Mosley T, Volcik K, Boerwinkle E, Ballantyne CM. Carotid intima-media thickness and presence or absence of plaque improves prediction of coronary heart disease risk: the ARIC (Atherosclerosis Risk In Communities) study. J Am Coll Cardiol. 2010 Apr 13;55(15):1600-7. doi: 10.1016/j.jacc.2009.11.075. — View Citation

Pencina MJ, D'Agostino RB Sr, Larson MG, Massaro JM, Vasan RS. Predicting the 30-year risk of cardiovascular disease: the framingham heart study. Circulation. 2009 Jun 23;119(24):3078-84. doi: 10.1161/CIRCULATIONAHA.108.816694. Epub 2009 Jun 8. — View Citation

Ray KK, Seshasai SR, Wijesuriya S, Sivakumaran R, Nethercott S, Preiss D, Erqou S, Sattar N. Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials. Lancet. 2009 May 23;373(9677):1765-72. doi: 10.1016/S0140-6736(09)60697-8. — View Citation

Störk S, van den Beld AW, von Schacky C, Angermann CE, Lamberts SW, Grobbee DE, Bots ML. Carotid artery plaque burden, stiffness, and mortality risk in elderly men: a prospective, population-based cohort study. Circulation. 2004 Jul 20;110(3):344-8. Epub 2004 Jul 6. — View Citation

Wagenknecht LE, Zaccaro D, Espeland MA, Karter AJ, O'Leary DH, Haffner SM. Diabetes and progression of carotid atherosclerosis: the insulin resistance atherosclerosis study. Arterioscler Thromb Vasc Biol. 2003 Jun 1;23(6):1035-41. Epub 2003 Apr 17. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Other Changes in fat intake Blood cell membrane fatty acid composition was measured by gas chromatography Baseline to 18 months No
Other Diet intake Food frequency questionnaire Serum and urine biomarkers Blood cell membrane fatty acid composition Baseline No
Primary Carotid Plaque presence(CP) To investigate CP prevalence differences between NEWDM and CONTROL subjects Baseline No
Primary Carotid Intima Media Thickness (CIMT) Compound CIMT (common carotid, bulb and internal carotid) differences between NEWDM and CONTROL. Baseline No
Secondary Changes in plaque height Baseline to 18 months No
Secondary Changes in CIMT at different territories Baseline to 18 months No
Secondary Changes in lifestyle Mediterranean Diet adherence and physical activity (validated questionnaires) Baseline to 18 months No
Secondary CIMT CIMT differences in different territories (common carotid, bulb and internal carotid) between NEWDM and CONTROL. Baseline No