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.

NCT ID: NCT02033278

Last Updated: 2020-09-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-06
• Study Completion Date: 2020-04-21

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.

Conditions

Idiopathic Dilated Cardiomyopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Infusion of autologous mononuclear bone marrow cells

Infusion of autologous mononuclear bone marrow cells plus conventional medical treatment (as indicated by clinician)

Group Type: EXPERIMENTAL

Infusion of autologous mononuclear bone marrow cells

Intervention Type: DRUG

Infusion of autologous mononuclear bone marrow cells plus conventional medical treatment (as indicated by clinician)

Placebo infusion

Placebo infusion plus conventional medical treatment (as indicated by clinician)

Group Type: PLACEBO_COMPARATOR

Placebo infusion

Intervention Type: DRUG

Placebo infusion plus conventional medical treatment (as indicated by clinician)

Interventions

Infusion of autologous mononuclear bone marrow cells

Infusion of autologous mononuclear bone marrow cells plus conventional medical treatment (as indicated by clinician)

Intervention Type: DRUG

Placebo infusion

Placebo infusion plus conventional medical treatment (as indicated by clinician)

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Iniciativa Andaluza en Terapias Avanzadas

OTHER

Sponsor Role: collaborator

Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Miguel Romero Moreno, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Reina Sofía

Manuel Sobrino Marquez, MD

Role: PRINCIPAL_INVESTIGATOR

Hospitales Universitarios Virgen del Rocío

Luis A Iñigo García, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Costa del Sol

Ricardo Zayas Rueda, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Puerta del Mar

Manuel De Mora Martín, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Regional U. Carlos Haya

Silvia López Fernández, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Virgen de las Nieves

José Francisco Díaz Fernández, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Juan Ramón Jimenez

Jesús Oneto Otero, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital de Jerez

Rafael Ruiz Salmerón, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Virgen Macarena

Locations

Hospital Universitario Puerta del Mar

Cadiz, , Spain

Hopistal Universitario Reina Sofía

Córdoba, , Spain

Hospital Universitario Virgen de las Nieves

Granada, , Spain

Hospital Universitario Juan Ramón Jimenez

Huelva, , Spain

Hospital de Jerez

Jerez de la Frontera, , Spain

Hospital Costa del Sol

Marbella, , Spain

Hospital Regional U. Carlos Haya

Málaga, , Spain

Hospital Universitario Virgen del Rocío

Seville, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Countries

Spain

References

Romero M, Suarez-de-Lezo J, Herrera C, Pan M, Lopez-Aguilera J, Suarez-de-Lezo J Jr, Baeza-Garzon F, Hidalgo-Lesmes FJ, Fernandez-Lopez O, Martinez-Atienza J, Cebrian E, Martin-Palanco V, Jimenez-Moreno R, Gutierrez-Fernandez R, Nogueras S, Carmona MD, Ojeda S, Cuende N, Mata R. Randomised, double-blind, placebo-controlled clinical trial for evaluating the efficacy of intracoronary injection of autologous bone marrow mononuclear cells in the improvement of the ventricular function in patients with idiopathic dilated myocardiopathy: a study protocol. BMC Cardiovasc Disord. 2019 Aug 22;19(1):203. doi: 10.1186/s12872-019-1182-4.

Reference Type: DERIVED

PMID: 31438858 (View on PubMed)

Other Identifiers

CMMo/MD/2013

Identifier Type: -

Identifier Source: org_study_id