Clinical trial NCT01086787: Paracrine Mechanisms of Bone Marrow Stem Cell Signalling in Chronic Heart Failure
Official title: Paracrine Mechanisms of Bone Marrow Stem Cell Signalling in Chronic Heart Failure
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Heart Failure
Keywords: Heart failure
Bone marrow
Bone marrow mononuclear cells
Surgery
Orthopedic surgery
Cardiac surgery
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2010-03-15
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Man and woman, undergoing cardiothoracic surgery, older than 18 years of age, with and without preserved left ventricular ejection fraction (LVEF \<40% and \>40%). Controls are man and women, older than 18 years of age, scheduled for orthopaedic surgery without a history of cardiac disease.

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Paracrine properties of bone marrow cells from patients with heart failure
timeFrame: 1 day
Secondary outcomes:
measure: To study preconditioning of different bone marrow stem cells with different cytokines
timeFrame: 1 day
measure: 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
timeFrame: 1 day
measure: To evaluate potential molecular mechanisms involved
timeFrame: 1 day
measure: To find mechanisms to enhance expansion of different bone marrow stem cells in vitro
timeFrame: 1 day
Other outcomes:
Locations:
city: Pavia
country: Italy
facility: Department of Heart, Blood and Lung , University of Pavia
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: W. T. Ruifrok, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center Groningen
name: R. A. de Boer, MD, PhD
role: STUDY_DIRECTOR
affiliation: University Medical Center Groningen
name: W. H. van Gilst, PhD
role: STUDY_CHAIR
affiliation: University of Pavia
name: M. Gnecchi, MD, PhD
role: STUDY_DIRECTOR
affiliation: University Medical Center Groningen
name: L. Kleijn, MD
role: PRINCIPAL_INVESTIGATOR
References: