Paracrine Mechanisms of Bone Marrow Stem Cell Signalling in Chronic Heart Failure

• Conditions: Heart Failure
• Interventions: Other: Surgery

• Registration Number: NCT01086787
• Lead Sponsor: University Medical Center Groningen

Brief Summary

The investigators hypothesize that chronic heart failure is associated with a general stem cell dysfunction, which translates into reduced paracrine function of adult stem cells from patients with chronic heart failure as compared to patients with preserved systolic function.

Detailed Description

Not available

Study Timeline

• Status Verified: 2010-03
• Study First Submitted: 2010-03-12
• Study First Submitted QC: 2010-03-12
• Study First Posted: 2010-03-15
• Last Update Submitted: 2010-06-10
• Last Update Posted: 2010-06-11
• Study Start: 2010-08
• Primary Completion: 2011-08
• Study Completion: 2011-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 125

Inclusion Criteria

For all participants:

1. Before any study-specific procedures, the appropriate written informed consent must be obtained.

2. Male and female older than 18 years of age.

   For the cardiac patients:

3. Being accepted for cardiothoracic surgery with the use of open chest surgery

4. A known left ventricular ejection fraction, either assessed by echocardiography, MUGA or MRI. If LVEF <40% a subject will be assigned to the chronic heart failure group, if LVEF >40% a subject will be assigned to the control group.

   For the non-cardiac patients:

5. Accepted for orthopedic surgery (e.g. total hip replacement) at the department of orthopedic surgery.

Exclusion Criteria

1. An unstable medical condition, defined as having been hospitalized for a non-cardiac condition within 4 weeks of screening, or otherwise unstable in the judgment of the investigator (e.g. at risk of complications or adverse events unrelated to study participation).

2. Younger than 18 years of age.

3. Clinical history of chronic kidney disease (at any point prior to registration).

4. Any known hepatic disease.

5. Recent (within 3 months) history of alcohol or illicit drug abuse disorder, based on self-report.

6. Clinically significant abnormality in chemistry, hematology, or urinalysis parameters performed within the screening period.

7. Participation in any investigational device or drug trial(s) or receiving investigational agent(s) within 30 days.

8. Any condition (e.g. psychiatric illness, etc.) or situation that, in the investigator's opinion, could put the subject at significant risk, confound the study results, or interfere significantly with the subject's participation in the study.

9. Legally incompetent adults, for which reason what so ever.

   For the non-cardiac patients:

10. A known history of cardiovascular disease.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Non heart failure patients	Surgery	Patients without heart failure undergoing open chest surgery
Heart failure patients	Surgery	Patients with heart failure undergoing open chest surgery.
Orthopedic patients	Surgery	Patients without heart failure undergoing orthopedic surgery

Primary Outcome Measures

Name	Time	Method
Paracrine properties of bone marrow cells from patients with heart failure	1 day	To compare the paracrine properties of bone marrow-derived stem cells harvested from patients suffering chronic heart failure vs healthy subjects. In particular, we aim to determine if the cytoprotective, pro-angiogenic and anti-fibrotic effects mediated by bone marrow stem cells of heart failure patients are similar to those from healthy patients.

Secondary Outcome Measures

Name	Time	Method
To study preconditioning of different bone marrow stem cells with different cytokines	1 day
To study in detail the temporal and spatial expression of paracrine factors in bone marrow stem cells in vitro, and to study the differences between bone marrow stem cells from patients with and without chronic heart failure	1 day
To evaluate potential molecular mechanisms involved	1 day
To find mechanisms to enhance expansion of different bone marrow stem cells in vitro	1 day

Trial Locations

Locations (2)

Department of Heart, Blood and Lung , University of Pavia; 🇮🇹 Pavia, Italy

University Medical Center Groningen; 🇳🇱 Groningen, Netherlands