BIO-2-HEART: Identification of Biomarkers in T2DM and Heart Failure

NCT03323216 | Recruiting

• 1 other identifier: 16-132
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

The primary aim of the current study is a better understanding of the role of Type 2 Diabetes Mellitus (T2DM) in heart failure and, in particular, changes in cardiac metabolism, which may contribute to heart failure. Various biomarkers in the coronary artery blood, as well as in the arterial and peripheral venous blood, are to be identified for this purpose. Included are patients with and without T2DM and with or without heart failure (HFpEF, HFmrEF, HFrEF), who have a clinically indicated and guidance-appropriate Cardiac Resynchronisation Therapy (CRT) implantation or pulmonary vein ablation/electrophysiological examination. Not all patients currently benefit from the implantation of a CRT system (so-called non-responder). Despite narrow inclusion criteria, these "non-responders" cannot be unmasked in advance of the implantation. A further aim of this study is to identify biomarkers, which can be determined in advance of implantation to differentiate between responders and non-responders.

Conditions

Heart Failure; Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (32)

• Oxygen partial pressure (pO2) [mmHg]

  Results of blood gas analysis: Oxygen partial pressure (pO2) \[mmHg\]

  Directly prior to the CRT-implantation

• Oxygen partial pressure (pO2) [mmHg]

  Results of blood gas analysis: Oxygen partial pressure (pO2) \[mmHg\]

  6 months after CRT-implantation

• Carbon dioxide partial pressure (pCO2) [mmHg]

  Results of blood gas analysis: Carbon dioxide partial pressure (pCO2) \[mmHg\]

  Directly prior to the CRT-implantation

• Carbon dioxide partial pressure (pCO2) [mmHg]

  Results of blood gas analysis: Carbon dioxide partial pressure (pCO2) \[mmHg\]

  6 months after CRT-implantation

• potential of hydrogen (pH) value [-]

  Results of blood gas analysis: pH value \[-\]

  Directly prior to the CRT-implantation

• potential of hydrogen (pH) value [-]

  Results of blood gas analysis: pH value \[-\]

  6 months after CRT-implantation

• Base excess [mmol]

  Results of blood gas analysis: Base excess \[mmol\]

  Directly prior to the CRT-implantation

• Base excess [mmol]

  Results of blood gas analysis: Base excess \[mmol\]

  6 months after CRT-implantation

• Lactate [mmol/l]

  Results of blood gas analysis: Lactate \[mmol/l\]

  Directly prior to the CRT-implantation

• Lactate [mmol/l]

  Results of blood gas analysis: Lactate \[mmol/l\]

  6 months after CRT-implantation

• Glucose [mg/dl]

  Results of blood gas analysis: Glucose \[mg/dl\]

  Directly prior to the CRT-implantation

• Glucose [mg/dl]

  Results of blood gas analysis: Glucose \[mg/dl\]

  6 months after CRT-implantation

• Electrolytes (K+, Na2+, Ca2+) [mmol/l]

  Results of blood gas analysis: Electrolytes (K+, Na2+, Ca2+) \[mmol/l\]

  Directly prior to the CRT-implantation

• Electrolytes (K+, Na2+, Ca2+) [mmol/l]

  Results of blood gas analysis: Electrolytes (K+, Na2+, Ca2+) \[mmol/l\]

  6 months after CRT-implantation

• High-sensitive troponin T [µg/L]

  Markers of myocardial ischemia and heart failure: High-sensitive troponin T \[µg/L\]

  Directly prior to the CRT-implantation

• High-sensitive troponin T [µg/L]

  Markers of myocardial ischemia and heart failure: High-sensitive troponin T \[µg/L\]

  6 months after CRT-implantation

• Total creatine kinase [µg/L]

  Markers of myocardial ischemia and heart failure: Total creatine kinase \[µg/L\]

  Directly prior to the CRT-implantation

• Total creatine kinase [µg/L]

  Markers of myocardial ischemia and heart failure: Total creatine kinase \[µg/L\]

  6 months after CRT-implantation

• Creatinine kinase-myocardial band (CK-MB) [µg/L]

  Markers of myocardial ischemia and heart failure: Creatinine kinase-myocardial band (CK-MB) \[µg/L\]

  Directly prior to the CRT-implantation

• Creatinine kinase-myocardial band (CK-MB) [µg/L]

  Markers of myocardial ischemia and heart failure: Creatinine kinase-myocardial band (CK-MB) \[µg/L\]

  6 months after CRT-implantation

• Aspartate aminotransferase [µg/L]

  Markers of myocardial ischemia and heart failure: Aspartate aminotransferase \[µg/L\]

  Directly prior to the CRT-implantation

• Aspartate aminotransferase [µg/L]

  Markers of myocardial ischemia and heart failure: Aspartate aminotransferase \[µg/L\]

  6 months after CRT-implantation

• Lactate dehydrogenase [µg/L]

  Markers of myocardial ischemia and heart failure: Lactate dehydrogenase \[µg/L\]

  Directly prior to the CRT-implantation

• Lactate dehydrogenase [µg/L]

  Markers of myocardial ischemia and heart failure: Lactate dehydrogenase \[µg/L\]

  6 months after CRT-implantation

• N-terminal pro-B-type natriuretic peptide (NT-proBNP) [µg/L]

  Markers of myocardial ischemia and heart failure: N-terminal pro-B-type natriuretic peptide (NT-proBNP) \[µg/L\]

  Directly prior to the CRT-implantation

• N-terminal pro-B-type natriuretic peptide (NT-proBNP) [µg/L]

  Markers of myocardial ischemia and heart failure: N-terminal pro-B-type natriuretic peptide (NT-proBNP) \[µg/L\]

  6 months after CRT-implantation

• High-sensitive C-reactive protein (CRP) [µg/L]

  Cytokines and inflammation markers: High-sensitive C-reactive protein (CRP) \[µg/L\]

  Directly prior to the CRT-implantation

• High-sensitive C-reactive protein (CRP) [µg/L]

  Cytokines and inflammation markers: High-sensitive C-reactive protein (CRP) \[µg/L\]

  6 months after CRT-implantation

• Procalcitonin (PCT) [µg/L]

  Cytokines and inflammation markers: Procalcitonin (PCT) \[µg/L\]

  Directly prior to the CRT-implantation

• Procalcitonin (PCT) [µg/L]

  Cytokines and inflammation markers: Procalcitonin (PCT) \[µg/L\]

  6 months after CRT-implantation

• Interleukin 6 (IL-6) [µg/L]

  Cytokines and inflammation markers: Interleukin 6 (IL-6) \[µg/L\]

  Directly prior to the CRT-implantation

• Interleukin 6 (IL-6) [µg/L]

  Cytokines and inflammation markers: Interleukin 6 (IL-6) \[µg/L\]

  6 months after CRT-implantation

Study Arms (3)

No diabetes

Patients without diabetes

Diagnostic Test: 6-minute walk test; Diagnostic Test: Study specific questionnaire; Procedure: Blood collection

Type 2 diabetes

Patients with diagnosis of type 2 diabetes (new/established)

Diagnostic Test: 6-minute walk test; Diagnostic Test: Study specific questionnaire; Procedure: Blood collection

Prediabetes

Patients with an intermediate state of hyperglycemia with glycemic parameters above normal but below the diabetes threshold.

Diagnostic Test: 6-minute walk test; Diagnostic Test: Study specific questionnaire; Procedure: Blood collection

Interventions

6-minute walk test DIAGNOSTIC_TEST

The 6-minute walk test is a functional test established in the clinic to assess the performance of a patient. The patient walks continuously for 6 minutes without interruption as far as possible. Breaks, speed changes and running are allowed. Test is performed prior the intervention and 6 months after the intervention.

No diabetes; Prediabetes; Type 2 diabetes

Study specific questionnaire DIAGNOSTIC_TEST

Study specific questionnaire The questionnaire is performed prior and 6 months after the intervention.

No diabetes; Prediabetes; Type 2 diabetes

Blood collection PROCEDURE

Blood collection during surgery: * coronary sinus * arterial * peripheral venous Blood collection 6 months after surgery: \- peripheral venous

No diabetes; Prediabetes; Type 2 diabetes

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with and without heart failure (HFrEF, HFmrEF, HFpEF) plus known status of type 2 diabetes (yes/no)

You may qualify if:

• guideline-appropriate clinical indication for CRT implantation/electrophysiologial examination/pulmonary vein ablation
• age of majority
• written declaration of consent
• persons who are able to work and mentally able to follow the instructions of the study staff
• free access routes

You may not qualify if:

• anemia Hb \<8 mg / dl
• patients with acute infectious disease (e.g. pneumonia)
• non-intubatable coronary sinus
• patients who do not have access to the subclavian vein (e.g. thrombosis of the subclavian vein or superior vena cava)
• patients with idiopathic hypertrophic, restrictive or constrictive cardiomyopathy, or heart failure due to a known inflammatory or infiltrating disease (e.g. amyloidosis, sarcoidosis) or a constrictive disease
• patients with heart failure by sepsis
• persons with acute myocardial ischaemia, e.g. by angina pectoris or ECG changes under load
• patients with acute coronary syndrome are not implanted in the past 3 months
• patients who were hospitalized during the last month due to heart failure and who had to be treated intravenously with diuretics or inotropic substances
• patients with mechanical aortic valve or tricuspid valve
• patients with heart transplant.
• patients with acute liver or renal failure
• pregnant and lactating women
• patients placed under an official or judicial order in an institution
• patients who are in a dependency or employment relationship with the sponsor or auditor

Sponsors & Collaborators

• RWTH Aachen University: lead

Study Sites (1)

University Hospital RWTH Aachen

Aachen, North Rhine-Westphalia, 52074, Germany

RECRUITING

Related Publications (10)

• Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016 Jul 14;37(27):2129-2200. doi: 10.1093/eurheartj/ehw128. Epub 2016 May 20. No abstract available.

  PMID: 27206819 BACKGROUND

• Askoxylakis V, Thieke C, Pleger ST, Most P, Tanner J, Lindel K, Katus HA, Debus J, Bischof M. Long-term survival of cancer patients compared to heart failure and stroke: a systematic review. BMC Cancer. 2010 Mar 22;10:105. doi: 10.1186/1471-2407-10-105.

  PMID: 20307299 BACKGROUND

• Bahtiyar G, Gutterman D, Lebovitz H. Heart Failure: a Major Cardiovascular Complication of Diabetes Mellitus. Curr Diab Rep. 2016 Nov;16(11):116. doi: 10.1007/s11892-016-0809-4.

  PMID: 27730517 BACKGROUND

• Kappel BA, Marx N, Federici M. Oral hypoglycemic agents and the heart failure conundrum: Lessons from and for outcome trials. Nutr Metab Cardiovasc Dis. 2015 Aug;25(8):697-705. doi: 10.1016/j.numecd.2015.06.006. Epub 2015 Jun 18.

  PMID: 26164634 BACKGROUND

• Sun H, Guan Y, Wang L, Zhao Y, Lv H, Bi X, Wang H, Zhang X, Liu L, Wei M, Song H, Su G. Influence of diabetes on cardiac resynchronization therapy in heart failure patients: a meta-analysis. BMC Cardiovasc Disord. 2015 Mar 21;15:25. doi: 10.1186/s12872-015-0018-0.

  PMID: 25880202 BACKGROUND

• Watson CJ, Ledwidge MT, Phelan D, Collier P, Byrne JC, Dunn MJ, McDonald KM, Baugh JA. Proteomic analysis of coronary sinus serum reveals leucine-rich alpha2-glycoprotein as a novel biomarker of ventricular dysfunction and heart failure. Circ Heart Fail. 2011 Mar;4(2):188-97. doi: 10.1161/CIRCHEARTFAILURE.110.952200. Epub 2011 Jan 31.

  PMID: 21282491 BACKGROUND

• Truong QA, Januzzi JL, Szymonifka J, Thai WE, Wai B, Lavender Z, Sharma U, Sandoval RM, Grunau ZS, Basnet S, Babatunde A, Ajijola OA, Min JK, Singh JP. Coronary sinus biomarker sampling compared to peripheral venous blood for predicting outcomes in patients with severe heart failure undergoing cardiac resynchronization therapy: the BIOCRT study. Heart Rhythm. 2014 Dec;11(12):2167-75. doi: 10.1016/j.hrthm.2014.07.007. Epub 2014 Jul 8.

  PMID: 25014756 BACKGROUND

• Costello-Boerrigter LC, Lapp H, Boerrigter G, Lerman A, Bufe A, Macheret F, Heublein DM, Larue C, Burnett JC Jr. Secretion of prohormone of B-type natriuretic peptide, proBNP1-108, is increased in heart failure. JACC Heart Fail. 2013 Jun;1(3):207-12. doi: 10.1016/j.jchf.2013.03.001. Epub 2013 Jun 3.

  PMID: 24621871 BACKGROUND

• Marques FZ, Vizi D, Khammy O, Mariani JA, Kaye DM. The transcardiac gradient of cardio-microRNAs in the failing heart. Eur J Heart Fail. 2016 Aug;18(8):1000-8. doi: 10.1002/ejhf.517. Epub 2016 Apr 12.

  PMID: 27072074 BACKGROUND

• Bergman BC, Tsvetkova T, Lowes B, Wolfel EE. Myocardial glucose and lactate metabolism during rest and atrial pacing in humans. J Physiol. 2009 May 1;587(Pt 9):2087-99. doi: 10.1113/jphysiol.2008.168286. Epub 2009 Mar 16.

  PMID: 19289551 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood

MeSH Terms

Conditions

Heart Failure; Diabetes Mellitus, Type 2

Interventions

Walk Test; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Exercise Test; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Clinical Laboratory Techniques; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Ben Kappel, MD PhD

  Uniklinik RWTH Aachen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ben Kappel, MD PhD

CONTACT

0241 800; bakppel@ukaachen.de

Christina Kalvelage, M. Sc.

CONTACT

0241 80 36485; ckalvelage@ukaachen.de

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 26, 2017
• First Posted: October 26, 2017
• Study Start: April 1, 2018
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 9, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)