Intravenous infusion of autologous mesenchymal stem cells from bone marrow for ALS patients: double-blind randomized controlled trial

JRCT ID: jRCT2013190010

Registered date:04/03/2020

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Amyotrophic Lateral Sclerosis (ALS)
• Date of first enrollment: 25/09/2020
• Target sample size: 40
• Study type: Interventional
• Intervention(s): Intravenous infusion of autologous mesenchymal stem cells derived from bone marrow

Outcome(s)

• Primary Outcome: The difference of change ratio of ALSFRS-R during 3 months before and after 90 days after first enrollment

Secondary Outcome

[Efficacy]- The difference of change ratio of MMT, grasping power , Norris scale, ALSAQ-40, %FVC
- The difference of change ratio of ALSFRS-R, MMT, grasping power , Norris scale, ALSAQ-40, %FVC between at 90days and 180days after enrollment
- The difference of change ratio of ALSFRS-R, MMT, grasping power , Norris scale, ALSAQ-40, %FVC between at 90days and 270days after enrollment
- The difference of change ratio of ALSFRS-R, MMT, grasping power , Norris scale, ALSAQ-40, %FVC at 3 months before enrollment and at 6months after enrollment
- The difference of change ratio of ALSFRS-R, MMT, grasping power , Norris scale, ALSAQ-40, %FVC at 3months before and after injection of the investigational product

[Safety]
- All adverse events rate during whole study period

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: < 80age old
• Gender: Both

Include criteria

[Inclusion criteria at the time of first registration]
(1) ALS that meets the diagnostic criteria (Updete Awaji ) as definite or probable
(2) ALS Severity is class1 to 3
(3) ALS onset within 3 years
(4) %FVC greater than or equal to 70%
(5) Completion of this trial is expected
(6) Age between 20 to 80
(7) The written informed consent obtained as much as possible from subjects. If the subject does not have ability to write etc, the written informed consent obtained from legal representative.

[Inclusion criteria at the time of second registration]
(1) ALS Severity is class1 to 3
(2) %FVC greater than or equal to 70%
(3) Completion of this trial is expected
(4) Ready to infuse of investigational product which satisfies specification of acceptance criteria
(5) Standard treatment (Riluzole, Edaravone,etc.) is not scheduled to change

Exclude criteria

[Exclusion criteria at the time of first registration]
(1) Bulbar paralysis related ALS or uncontrollable mental symptoms
(2) Diagnosed as dementia
(3) Diagnosed as HBV, HCV, HIV, HTLV-1, syphilis or Human parvovirus B19 by initial screening
(4) Pancytopenia (WBC <2000/uL, Hb <10.0g/dl, Plt <100000/uL)
(5) Past history of neoplasms (except CR), severe diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism, severe mental and behavioural disorders, severe diseases of the nervous system, severe congenital malformations, deformations and chromosomal abnormalities
(6) Past history of penicillin and streptomycin allergy or other severe allergy (shock, anaphylactoid symptoms etc.)
(7) Poor general condition due to [Endocrine, nutritional and metabolic diseases, Mental disorders, diseases of nervous system, diseases of circulatory system (Uncontrollable and refractory heart failure, moderate or severe valvular heart disorder, uncontrollable and refractory atrial fibrillation, refractory atrial and ventricular thrombus, history of ischemic heart disease and PCI within the past 12 months, serious arrhythmia), diseases of the respiratory system, diseases of the digestive system, diseases of the musculoskeletal system and connective tissue, diseases of the genitourinary system (dialysis etc), injury, poisoning and certain other consequences of external causes etc]
(8) Intracranial lesion (severe asymptomatic lesion, severe old infarction, severe white matter lesion, severe multiple lesions, severe microbleeding or multiple hemosiderosis, Cerebrovascular diseases such as Moyamoya disease or high risk AN etc, severe intracerebral hemorrhage etc) including past history of these issues.
(9) 70% or more stenosis or dissecting in the artery causing cerebral infarction even though after revascularization (except complete thrombotic occlusion)
(10) Severe arteriosclerotic change and calcification in the blood vessels of head and neck.
(11) Preoperative possible uncontrollable HT under depressor therapy (systolic pressure more than 140mmHg, diastolic pressure more than 90mmHg)
(12) Participation in other clinical trials or past history of cellular therapy
(13) Pregnant or possibly pregnant, nursing women or those who plan to be pregnant during the study period or male patients who wish partner to get pregnant
(14) Other patients judged by investigators as inappropriate for this study

[Exclusion criteria at the time of second registration]
(1) Past history of neoplasms (except CR), severe diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism, severe mental and behavioural disorders, severe diseases of the nervous system, severe congenital malformations, deformations and chromosomal abnormalities
(2) Past history of penicillin and streptomycin allergy or other severe allergy (shock, anaphylactoid symptoms etc.)
(3) Poor general condition due to [Endocrine, nutritional and metabolic diseases, Mental disorders, diseases of nervous system, diseases of circulatory system (Uncontrollable and refractory heart failure, moderate or severe valvular heart disorder, uncontrollable and refractory atrial fibrillation, refractory atrial and ventricular thrombus, history of ischemic heart disease and PCI within the past 12 months, serious arrhythmia), diseases of the respiratory system, diseases of the digestive system, diseases of the musculoskeletal system and connective tissue, diseases of the genitourinary system (dialysis etc), injury, poisoning and certain other consequences of external causes etc]
(4) Intracranial lesion (moderate asymptomatic lesion, old infarction, white matter lesion, multiple lesions, microbleeding or multiple hemosiderosis, Cerebrovascular diseases such as Moyamoya disease or AN etc, severe intracerebral hemorrhage etc)
(5) 70% or more of stenosis or dissecting in the artery causing cerebral infarction even though after revascularization (except complete thrombotic occlusion)
(6) Severe arteriosclerotic change and calcification
(7) Preoperative possible uncontrollable hypertension under depressor therapy
(8) Pregnant, nursing women or those who plan to be pregnant during the study period or male patients who wish partner to get pregnant
(9) Other patients judged by investigators as inappropriate for this study

Related Information

• Primary Sponsor: HISAHARA SHIN
• Source(s) of Monetary Support: Sapporo Medical University