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

NCT ID: NCT03323216

Last Updated: 2024-05-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

400 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-04-01

Study Completion Date

2026-12-31

Brief Summary

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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.

Detailed Description

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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, who have a clinically indicated and guidance-appropriate Cardiac Resynchronisation Therapy (CRT) implantation due to their cardiac insufficiency and patients who have a clinically indicated electrophysiological examination (EPU) or pulmonary vein ablation (PVI).

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. Thus, 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.

Patient selection is based on the previously defined inclusion and exclusion criteria. The patient is informed by the physician and gives written consent to participate in the study. Prior to the implantation of the CRT system/the electrophysiological examination(EPU)/pulmonary vein ablation(PVI), the patient first responds to a study-related questionnaire and performs a 6-minute walk test.

Afterwards the clinically indicated, elective CRT implantation/EPU/PVI is performed by experienced physicians of the Medical Clinic I. Routinely, an arterial pressure catheter for invasive blood pressure monitoring (usually arteria radialis) is inserted. In addition, 2 peripheral venous accesses are established. The system of the CRT system is carried out via a small pectoral section. The cardiac probes are inserted into the heart via the subclavian vein. First, the probe is implanted in the right ventricle and, if necessary, a probe is placed in the right atrium. For EPU/PVI a femoral vein acsess is established.

To establish the coronary sinus (CS) probe, the intubation of the coronary sinus is performed by means of a guide catheter, which can be used to take blood samples. After intubation of the coronary sinus, the coronary artery blood is taken from the guide catheter for the study as well as arterially via the underlying pressure catheter as well as peripheral venous over a horizontal venous catheter. During EPU/PVI the coronary sinus has also to be intubated due to the ablation protocol. The blood sampling does not take more than 1-2 minutes.

The surgery is then terminated as planned and postoperative care is performed according to the standard operation procedure (SOP) of the Medical Clinic I. Within the framework of a control visit routinely performed in the Medical Clinic I , an echocardiographic follow-up of heart failure, a history assessment and a laboratory-based blood analysis are performed 6 months after CRT implantation. In the context of this visit peripheral venous blood is collected again for the study. In addition, the 6-minute walk test is performed once more and the patient receives the same questionnaire again.

Laboratory routine blood analysis is performed in the central laboratory of the University Hospital of Aachen and is independent of the study. The analysis measures standard parameters such as electrolytes, blood count, retention parameters, glucose, HbA1c, liver values, N-terminal Brain Natriuretic Peptide (NT-pro-BNP) etc. .

A blood gas analysis of the study blood is performed out first. The remaining blood is processed and stored at -80 ° C, so-called "biobank", for further biomarker analysis, e.g. metabolite analysis, peptides/proteins and RNA.

Conditions

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Heart Failure Diabetes Mellitus, Type 2

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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No diabetes

Patients without diabetes

6-minute walk test

Intervention Type 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.

Study specific questionnaire

Intervention Type DIAGNOSTIC_TEST

Study specific questionnaire

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

Blood collection

Intervention Type PROCEDURE

Blood collection during surgery:

* coronary sinus
* arterial
* peripheral venous

Blood collection 6 months after surgery:

\- peripheral venous

Type 2 diabetes

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

6-minute walk test

Intervention Type 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.

Study specific questionnaire

Intervention Type DIAGNOSTIC_TEST

Study specific questionnaire

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

Blood collection

Intervention Type PROCEDURE

Blood collection during surgery:

* coronary sinus
* arterial
* peripheral venous

Blood collection 6 months after surgery:

\- peripheral venous

Prediabetes

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

6-minute walk test

Intervention Type 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.

Study specific questionnaire

Intervention Type DIAGNOSTIC_TEST

Study specific questionnaire

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

Blood collection

Intervention Type PROCEDURE

Blood collection during surgery:

* coronary sinus
* arterial
* peripheral venous

Blood collection 6 months after surgery:

\- peripheral venous

Interventions

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6-minute walk 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.

Intervention Type DIAGNOSTIC_TEST

Study specific questionnaire

Study specific questionnaire

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

Intervention Type DIAGNOSTIC_TEST

Blood collection

Blood collection during surgery:

* coronary sinus
* arterial
* peripheral venous

Blood collection 6 months after surgery:

\- peripheral venous

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

1. anemia Hb \<8 mg / dl
2. patients with acute infectious disease (e.g. pneumonia)
3. non-intubatable coronary sinus
4. patients who do not have access to the subclavian vein (e.g. thrombosis of the subclavian vein or superior vena cava)
5. 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
6. patients with heart failure by sepsis
7. persons with acute myocardial ischaemia, e.g. by angina pectoris or ECG changes under load
8. patients with acute coronary syndrome are not implanted in the past 3 months
9. patients who were hospitalized during the last month due to heart failure and who had to be treated intravenously with diuretics or inotropic substances
10. patients with mechanical aortic valve or tricuspid valve
11. patients with heart transplant.
12. patients with acute liver or renal failure
13. pregnant and lactating women
14. patients placed under an official or judicial order in an institution
15. patients who are in a dependency or employment relationship with the sponsor or auditor
16. taking an investigational medicinal product 30 days before the start of the study
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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RWTH Aachen University

OTHER

Sponsor Role lead

Responsible Party

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Ben Kappel

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ben Kappel, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Uniklinik RWTH Aachen

Locations

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University Hospital RWTH Aachen

Aachen, North Rhine-Westphalia, Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Ben Kappel, MD PhD

Role: CONTACT

Christina Kalvelage, M. Sc.

Role: CONTACT

0241 80 36485

Facility Contacts

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Ben A Kappel, MD PhD

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 27206819 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20307299 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27730517 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26164634 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25880202 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21282491 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25014756 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24621871 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27072074 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19289551 (View on PubMed)

Other Identifiers

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16-132

Identifier Type: -

Identifier Source: org_study_id

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