Brief Title
Infusion Intracoronary of Mononuclear Autologous Adult no Expanded Stem Cells of Bone Marrow on Functional Recovery in Patients With Idiopathic Dilated Cardiomyopathy and Heart Failure.
Official Title
Multicenter Phase IIb Clinical Trial, Double-blind, Randomized, Controlled Placebo for to Assess the Efficacy of Intracoronary Infusion of Autologous Adult Stem Cells Mononuclear Marrow Unexpanded on Functional Recovery in Patients With Idiopathic Dilated Cardiomyopathy and Heart Failure.
Brief Summary
Clinical trial phase IIb, double-blind, randomized, controlled with placebo. There is
sufficient preliminary evidence to consider intracoronary injection of bone marrow progenitor
cells as a viable, safe and beneficial treatment in patients with dilated cardiomyopathy,
although the biological mechanism of action of bone marrow cells in the myocardium is not
known. In this project we propose to investigate comparatively and from a biological and
clinical point of view the applicability of regenerative therapy with autologous bone marrow
cells in patients with dilated cardiomyopathy.
Detailed Description
The study population correspond to male and female patients with idiopathic dilated
cardiomyopathy.
51 patients diagnosed with this disease are included. After inclusion, will proceed to the
random allocation to study group or control group in a 2:1 ratio, 34 patients in the
treatment group and 17 in the control group.
The total duration is expected to be 48 months: The inclusion period is 24 months and each
patient assigned to the experimental group will be followed for 24 months, whereas that one
ramdomized to the control group, will have a folow-up of 12 months. Upon completion there of,
the patients will be followed in routine clinical practice.
This is a double blind study, in which all patients will perform the bone marrow harvesting.
All patients will receive the best medical treatment individualized (ACEIs or Angiotensin II
receptor blocker, beta-blockers, diuretics and eplerenone) for at least 6 months prior to
their participation in the clinical trial, so that the situation is stable and
pharmacological basal condition is the same for everyone.
The bone marrow cells of patients assigned to placebo group will be cryopreserved, and once
the trial is completed, the blind will be opened and all the patients who had been randomized
to the control group, may be processed by the route of compassionate use with their own
mononuclear bone marrow cells previously frozen.
The patients who are randomized to experimental group will be treated by the conventional
treatment + infusion of autologous mononuclear bone marrow cells not expanded whereas the
patients who are randomized to control group will be treated by the conventional treatment +
infusion of placebo.
The main objective is to assess comparative the efficacy of intracoronary injection of bone
marrow stem cells autologous to improve ventricular function in patients with idiopathic
dilated cardiomyopathy who receive conventional medical treatment, compared with a control
group who receive a infusion of placebo and conventional medical treatment. The improvement
in ventricular function assessed by changes in angiographically determined ejection fraction.
Secondary objectives of the study are:
- To analyze the predictors of good clinical response, functional and biological treatment
with adult stem cells autologous mononuclear bone marrow not expanded in terms of functional
recovery.
The following parameters were evaluated: Functional class (NYHA), Natriuretic peptide B,
Stress test (exercise time), Echocardiographic parameters of ventricular function, for
example LVEF (%), TDV (ml), TSV (ml) and TAPSE (ms) and Biological parameters of cellular
functionality, for example CD133 +, CD34 +, CD34 +/CD177 + and CD34 +/CD38- (in %).
- To determine, in the light of the obtained results, the application protocol suitable cell
therapy for the treatment of dilated cardiomyopathy.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Changes in ventricular function measured angiographically.
Secondary Outcome
Degree of clinical improvement based on the absence of major cardiac events (MACE) during follow-up.
Condition
Idiopathic Dilated Cardiomyopathy
Intervention
Infusion of autologous mononuclear bone marrow cells
Study Arms / Comparison Groups
Infusion of autologous mononuclear bone marrow cells
Description: Infusion of autologous mononuclear bone marrow cells plus conventional medical treatment (as indicated by clinician)
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
27
Start Date
January 6, 2014
Completion Date
April 21, 2020
Primary Completion Date
October 19, 2018
Eligibility Criteria
Inclusion Criteria:
1. Patients of both sexes and ages between 18 and 70 years.
2. Patients diagnosed with dilated cardiomyopathy established by echocardiography.
3. Minimum evolution since diagnosis of 6 months.
4. Absence of coronary injury tested with multislice CT and/or hemodynamic study
performed after study entry, or within the previous 36 months (or before in specific
low risk clinical profiles) if no angina symptomatology is present.
5. Patients receiving optimized medical therapy for at least 6 months prior to enrollment
(individually adjusted according to functional status).
6. Ejection fraction of the left ventricle <40% or ejection fraction of the left
ventricle 40% -50% if left ventricular tele-diastolic volume is > 110 ml/m2.
7. Presence of sinus rhythm.
8. Writen informed consent for participation in the trial.
9. Normal laboratory parameters, defined by: Leukocytes ≥ 3000; Neutrophils ≥ 1500;
Platelets ≥ 100,000; Aspartate aminotransferase / Alanine aminotransferase ≤ 2.5
standard range institution; Creatinine ≤ 2.5 mg / dL; Haemoglobin > 9 g/dL
10. Women of childbearing potential must have negative results on a pregnancy test and
agree to use medically approved methods of contraception thoughout follow up.
Exclusion Criteria:
1. Secondary Dilated cardiomyopathy.
2. Recent history of myocarditis (< 6 months prior to study entry).
3. Patients amenable to receive cardiac resynchronization therapy
4. Patients in active waiting list for heart transplantation.
5. Coexistence of other serious systemic diseases.
6. Coexistence of any type of blood disease
7. Pregnant or breastfeeding women; or women of childbearing potential not comminting to
use effective contraception.
8. Patients who are currently participating, or have completed their participation in a
clinical trial within the last 3 months. Patients who have participated in any
advanced therapies clinical trial any time previously.
9. Patients with malignant or pre-malignant tumors.
10. Positive serology for hepatitis B virus, hepatitis C virus or human immunodeficiency
virus.
11. Use of any protocolo prohibited medication. A wash-out period of 2 months can be
considered for inclusion in the trial.
Gender
All
Ages
18 Years - 70 Years
Accepts Healthy Volunteers
No
Contacts
Miguel Romero Moreno, MD, PhD, ,
Location Countries
Spain
Location Countries
Spain
Administrative Informations
NCT ID
NCT02033278
Organization ID
CMMo/MD/2013
Responsible Party
Sponsor
Study Sponsor
Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
Collaborators
Iniciativa Andaluza en Terapias Avanzadas
Study Sponsor
Miguel Romero Moreno, MD, PhD, Principal Investigator, Hospital Universitario Reina Sofía
Verification Date
September 2020