Clinical trial NCT06361433: Intracerebral Transplantation of Autologous MSC Combined With Scaffold Product for Chronic Intracerebral Hemorrhage
Official title: Phase I/II Trial of Intracerebral Transplantation of Autologous Bone Marrow Stromal Cells Combined With Recombinant Peptide Scaffold for Patients With Chronic Intracerebral Hemorrhage
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Intracerebral Hemorrhage
Keywords: Mesenchymal stromal cell
scaffold
chronic
intracerebral hemorrhage
intraparenchymal transplantation
Lead sponsor: Hokkaido University Hospital
Sponsor class: OTHER
Collaborators: name: Japan Agency for Medical Research and Development
First posted: 2024-04-11
Enrollment: 8
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to test intracerebral transplantation of stem cell product in patient with chronic intracerebral hemorrhage. The main questions aims to answer are:

* The safety of the product
* The efficacy of the product

Detailed description: Introduction:

Intracerebral hemorrhage stands as a leading global cause of death and disability, posing a significant challenge with limited treatment options, especially for chronic patients. Recent advances of stem cell therapies have opened new avenues for therapeutic potential. The investigators' previous preclinical research has demonstrated that intracerebral transplantation of bone marrow stromal cells (BMSCs) combined with a recombinant human collagen type I scaffold enables higher cell survival and engraftment, holds promising potential. The investigators present the protocol for a novel clinical trial, named "Research on Advanced Intervention using Novel Bone Marrow Stem Cells for Chronic Intracerebral Hemorrhage" (RAINBOW-Hx).

Methods and Analysis:

RAINBOW-Hx is a phase I/II, open-label, uncontrolled study with the primary objective of assessing the safety and efficacy of intracerebral transplantation of autologous BMSCs combined with the scaffold (HUFF-01) in patients with chronic intracerebral hemorrhage. Eight patients, experiencing moderate to severe neurological deficits for 12 months or longer, will be enrolled. The hemorrhage location will be limited to the basal ganglia and thalamus. Approximately 50 mL of bone marrow will be extracted from the iliac bone of each patient, and BMSCs will be cultured using autologous platelet lysate. Three days before transplantation, BMSCs will be combined with the scaffold to generate HUFF-01. Each patient will receive a 50,000 HUFF-01 dose, containing approximately 50 million BMSCs, through stereotactic transplantation into the hemorrhagic cavity. Neurological assessments, magnetic resonance imaging, 18F-fluorodeoxyglucose positron emission tomography, and 123I-Iomazenil single-photon emission computed tomography will be performed for one year after administration.

Eligibility criteria: Inclusion Criteria:

* 1. Age between 20 and 70 years
* 2. Clinical diagnosis of intracerebral hemorrhage 12 month or more from onset
* 3. Hemorrhagic location of unilateral basal ganglia or thalamus
* 4. Moderate to severe neurological symptoms; mRS 3 or 4, and Brunnstrom stage Ⅲ or IV
* 5. No significant neurological impairment before hemorrhage (Pre-hemorrhagic mRS of 0 or 1)
* 6. Subjects who can give informed consent by its self

Exclusion Criteria:

* 1. Severe microbleeds found by T2\*
* 2. Hemorrhagic cavity less than 2 mL
* 3. The hemorrhage is due to arteriovenous malformation, cerebral aneurysm, and Moyamoya disease
* 4. Subject showing obvious communication between the hemorrhagic cavity and lateral ventricle on MRI
* 5. Subject showing severe lower extremity contracture (Maximum knee extension less than -15 degrees, Maximum ankle flexion less than 0 degree)
* 6. Subject's body weight less than 45 kg for male and 40kg for female
* 7. Anaemia (Hg \< 10·0 g/dL)
* 8. Thrombocytopaenia (platelet count \< 100,000/mm3)
* 9. Severe heart disease (ischaemic heart disease, heart failure)
* 10. Uncontrolled hypertension, despite antihypertensive therapy
* 11. Carriers of infectious disease: syphilis, HBV, HCV, HIV-1/HIV-2, HTLV-1, parvovirus B19
* 12. Pregnant or lactating or expecting to become pregnant during the study
* 13. History of malignancy
* 14. Systemic organ failure ALT ≤ 3·0× upper limit of normal Total bilirubin ≤ 1·5× upper limit of normal Serum creatinine ≤ 1·5× upper limit of normal
* 15. Known serious allergy to any agents used in the study
* 16. Contraindication for magnetic resonance imaging
* 17. Any condition that in the judgement of the investigator would place the patient at undue risk

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: one year
Secondary outcomes:
measure: Change in mRS examination
timeFrame: One year
measure: Change in NIHSS examination
timeFrame: One year
measure: Change in FIM examination
timeFrame: One year
measure: Change in Fugl-Myer examination
timeFrame: One year
measure: Change in Barthal index examination
timeFrame: One year
measure: Change in FDG-PET examination
timeFrame: One year
measure: Change in IMZ-SPECT examination
timeFrame: One year
Other outcomes:
Locations:
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
Study officials:
References: