The main objective is assessment of safety and feasibility of intravenous administration of autologous, in vitro expanded, mesenchymal stem cells in patients with pulmonary arterial hypertension due to systemic sclerosis. The secondary objective is…
ID
Source
Brief title
Condition
- Heart failures
- Pulmonary vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The administration of autologous bone marrow-derived in vitro expanded
mesenchymal stem cells will be considered feasible if all the procedures in the
protocol can be performed as described. Safety will be reflected as the rate of
(serious) adverse events in the study population during a follow up of 3
months.
Secondary outcome
Preliminary efficacy will be described as change in quality of life, functional
class, exercise capacity, pro-brain natriuretic peptide levels,
electrocardiographic and echocardiographic characteristics, and pulmonary
function and pulmonary pressure measurements before and after the procedure.
Background summary
In patients with systemic sclerosis, pulmonary arterial hypertension has a poor
prognosis with a one-year mortality rate of 30%. Despite optimal
pharmacological treatment, patients experience daily complaints. Hence, new
treatment regiments are needed. In preclinical studies it is suggested that
intravenous administration of autologous bone marrow-derived mesenchymal stem
cells can be a potential treatment option.
Study objective
The main objective is assessment of safety and feasibility of intravenous
administration of autologous, in vitro expanded, mesenchymal stem cells in
patients with pulmonary arterial hypertension due to systemic sclerosis. The
secondary objective is preliminary assessment of efficacy.
Study design
In the proposed pilot study 7 patients with systemic sclerosis and pulmonary
arterial hypertension will be enrolled. 100 millilitres of bone marrow will be
aspirated from the iliac crest. Mesenchymal stem cells will be separated with
ficol density gradient and expanded ex vivo. After approximately 9 weeks a dose
of .5-2*10^6 cells/ kg bodyweight will be administrated intravenously.
Intervention
Bone marrow will be aspirated from the iliac crest. Expanded mesenchymal stem
cells will be administrated intravenously and reach the pulmonary circulation
through the the right side of the heart.
Study burden and risks
Because of the poor prognosis with a one-year mortality rate of 30% in
patients with systemic sclerosis and pulmonary arterial hypertension, there is
a need for new treatment options. Since pre-clinical studies suggest a
positive effect and previous studies did not show severe die effects in human
after peripheral administartion of MSC's, it seems justifiable to investigate
whether this patient population might benefit from this treatment.
Risks:
On beelding and infection after invasive procedures
Rontgen radiation exposure (catheterization, X-thorax en CT-thorax)
Complications catheterization ( Nederlandse hartstichting)
albinusdreef 2
Leiden 2333za
NL
albinusdreef 2
Leiden 2333za
NL
Listed location countries
Age
Inclusion criteria
- Pulmonary arterial hypertension, defined as a mean pulmonary artery pressure (mPAP) *25mmHg at rest with a pulmonary capillary wedge pressure (PCWP) of <15 mmHg.
- Systemic sclerosis, diagnosed according to the criteria for the classification of systemic sclerosis by The American College of Rheumatology
- Optimal medical PAH treatment
- Age * 18 years and life expectancy more than 3 months
- Able and willing to undergo catheterisation and echocardiography
- Written informed consent
- Pulmonary and haemodynamic stable for at least 3 months
- NYHA functioning class *2
Exclusion criteria
- Evidence of cancer in past 5 years (except low grade and fully resolved non-melanoma skin malignancy)
- Concurrent participation in a study using an experimental drug or an experimental procedure within 2 months before the administration procedure.
- Suspected presence of pulmonary hypertension caused by left heart disease resulting in an increased wedge pressure (group II,Nice 2013(8))
- Suspected presence of pulmonary hypertension due to pulmonary disease and/or hypoxia (group III, Nice 2013 (8)), as assessed by our PAH working group.
- Other severe concurrent illnesses (including active infection).
- Bleeding diathesis, infection with the human immunodeficiency virus (HIV) or pregnancy.
- Any other condition that, in the opinion of the investigator, could pose a significant threat to the subject if the investigational therapy would be initiated.
- Inability to undergo cardiac catheterization.
- Inability to follow the protocol and comply with follow-up requirements.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-003133-26-NL |
| CCMO | NL50143.000.14 |