E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ischemic stroke |
Ictus isquémico |
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E.1.1.1 | Medical condition in easily understood language |
ischemic stroke |
Ictus isquémico |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061256 |
E.1.2 | Term | Ischaemic stroke |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy in the intra-arterial infusion with mononuclear autologous bone marrow stem cells in patients with ischemic stroke, by the evaluation of the functional recovering after infusion |
Valorar la eficacia del tratamiento con células madre de médula ósea en pacientes con ictus isquémico agudo, mediante la evaluación de la recuperación funcional tras el procedimiento. |
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E.2.2 | Secondary objectives of the trial |
To validate the safety and feasibility, previously demonstrated clinic and experimentally, of the intra-arterial infusion of autologous bone marrow stem cells in patients with ischemic stroke acute and disabling neurological deficit, evaluating the possible appearance of adverse effects and toxicity derived from the treatment. To evaluate the changes produced after the treatment, with structurally neuroimagen (Magnetic Resonance), assessing the size of injured area as well as the perilesional atrophy. To confirm the modification in the serum levels of growth factors as the NGF (nerve growth factor). To evaluate the modifications induced in the cerebral perfusion by Cerebral Magnetic Resonance, after the above mentioned treatment. To confirm the relation observed in the previous study between the numbers of CD34 + infused and Barthel's index. |
?Validar la seguridad y viabilidad, previamente demostrada clínica y experimentalmente, de la inyección intra-arterial de células madre de médula ósea autólogas en pacientes con ictus isquémico agudo y déficit neurológico incapacitante, valorando la posible aparición de efectos adversos y toxicidad derivados del tratamiento. ?Evaluar los cambios producidos tras el tratamiento, con neuroimagen estructural (Resonancia Magnética), tanto del tamaño del infarto como de la atrofia perilesional. ?Evaluar las modificaciones inducidas en la perfusión cerebral mediante Resonancia Magnética cerebral, tras dicho tratamiento. ?Confirmar la relación observada en el estudio piloto entre el número de CD34+ infundidas y el índice de Barthel. ?Confirmar la relación observada en el estudio piloto entre el número de CD34+ infundidas y el índice de Barthel. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients of both sexes with age between 18 and 80 years old. 2. Clinical and radiological diagnosis of ischemiac stroke in the MCA (Middle Cerebral Artery) territory after 24 hours of beginning and with not more than 7 days after the appearance of the symptoms. 3. Radiological diagnosis of cerebral stroke and MCA's permeability by magnetic resonance/angio magnetic resonance (RM/aRM). 4. Scale of NIHSS's neurological deficit (National Institutes of Health Stroke Scale) of more than 6 points and up to 20. 5. Loss of strength of at least 2 points in motive articles in NIHSS except in the cases of aphasia. |
1.Pacientes de ambos sexos con edad comprendida entre 18 y 80 años. 2. Diagnóstico clínico y radiológico de infarto isquémico en territorio de ACM después de 24 horas de inicio y con no más de 7 días después de la aparición de los síntomas. 3.Diagnóstico radiológico de infarto cerebral y permeabilidad de ACM por resonancia magnética/angio resonancia magnética (RM/aRM). 4.Escala de déficit neurológico de NIHSS (National Institutes of Health Stroke Scale) de más de 6 puntos y hasta 20. 5.Pérdida de fuerza de al menos 2 puntos en ítems motores en NIHSS excepto en los casos de afasia pura |
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E.4 | Principal exclusion criteria |
1. Disability or contraindication for the angiographic examination including the suspection in arterial dissection; 2.Hemorrhagic Ictus or stroke with hemorrhagic symptomatic transformation. 3. Patients with lacunar stroke. 4. Worsening in NIHSS's scale of 4 points or more in 24 hours before the treatment, attributable to edema and / or cerebral hemorrhage or suspectious in development of malignant stroke of middle cerebral artery. 5. Deficit in the Glasgow comma scale lower than 8 points; 6. Impossibility or contraindication for MR's acghivement; 7. Patients with malignant tumors, except basocelullar carcinoma 8. Punctuation in the modified Rankin scale previous to stroke equal or higher than 2. 9. Neurodegenerative diseases; 10. Unbalanced or acute cardiac insufficiency 11. Coexistence of any type of hematologic disease; 12. Contraindication for the puncture of bone marrow; 13. Clot related diseases 14. Hepatic insufficiency 15. Renal moderate insufficiency (creatinine higher of 2 mg / dl); 16. Concomitant serious diseases; 17. Pregnant women, in period of lactation, or in fertile age that they are not using a contraceptive effective method; 18. Patients who are currently enrolled or have been dismissed by a 3 months period. |
1.Incapacidad o contraindicación para el examen angiográfico incluyendo sospecha de disección arterial; 2.Ictus hemorrágico o infarto con transformación hemorrágica sintomática. 3.Pacientes con infarto lacunar. 4.Empeoramiento en la escala de NIHSS de 4 puntos o más en las 24 horas previas al tratamiento, atribuible a edema y/o hemorragia cerebral o sospecha de desarrollo de infarto maligno de arteria cerebral media. 5.Déficit en la escala de coma de Glasgow inferior a 8 puntos; 6.Imposibilidad o contraindicación para la realización de RM; 7.Pacientes con tumores malignos, excepto carcinoma basocelular; 8.Puntuación en la escala de Rankin modificada previa al ictus mayor o igual a 2. 9.Enfermedades neuro-degenerativas; 10.Insuficiencia cardíaca descompensada o aguda 11.Coexistencia de cualquier tipo de enferemdad hematológica; 12.Contraindicación para la punción de médula ósea; 13.Coagulopatías; 14.Insuficiencia hepática; 15.Insuficiencia renal moderada (creatinina mayor de 2 mg / dl); 16.Enfermedades concomitantes graves; 17.Mujeres embarazadas, en periodo de lactancia, o en edad fértil que no estén usando un método anticonceptivo eficaz; 18.Pacientes que estén actualmente participando o hayan finalizado su participación en un ensayo clínico en un periodo inferior a 3 meses. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The main variable of the study will be the number of patients that reach the functional independence (scale modified of Rankin 0-2) after 6 months of the treatment |
La variable principal del estudio será la proporción de pacientes que alcanzan la independencia funcional (escala modificada de Rankin 0-2) después de 6 meses del tratamiento |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary variables of efficiency: ?Improvement in the scale between the baseline period and 3 and 6 months, and between both groups, control and active arm. ? Independence in Barthel's scale (Barthel> 90). Between the baseline period and 3 and 6 months, and between both groups, control and active arm. ? Volume of stroke (diffusion in MR) - final volume of the stroke (FLAIR in MR) to 180 days between both groups, control and active arm.
Secondary variables of efficiency: ? Mortality ?Tumorigenesis ?Cerebral hemorrhage ?Convulsions ? Record of vital signs (BP, HR), blood test (haemogram, ionogram, renal, biochemistry) and presence of complications related to the procedures of the trial (puncture of the hip iliac crest, catheterizations) besides the record of adverse events. |
Constituyen variables secundarias de eficacia: ?Mejora en la escala de NIHSS entre el momento basal y los 3 y 6 meses, y entre los dos grupos, control y experimental. ?Independencia en la escala de Barthel (Barthel>90). entre el momento basal y los 3 y 6 meses, y entre los dos grupos, control y experimental. ?Volumen de infarto (difusión en RM)-Volumen final del infarto (FLAIR en RM) a los 180 días entre los dos grupos, control y experimental.
Constituyen variables secundarias de seguridad:
?Mortalidad ?Tumorgenesis ?Hemorragia cerebral ?Convulsiones ?Registro de constantes vitales (TA, FC), parámetros analíticos (hemograma, ionograma, función renal, bioquímica) y presencia de complicaciones relacionadas con los procedimientos del ensayo (punción de cresta iliaca, cateterismos) además del registro de acontecimientos adversos. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
tratamiento médico convencional |
Standart treatment |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS |
última visita de seguimiento del último paciente |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |