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The Evaluation of the Effect of Mesenchymal Stem Cells on the Immune System of Patients With ALS (ALSTEM)

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ClinicalTrials.gov Identifier: NCT04651855
Recruitment Status : Recruiting
First Posted : December 3, 2020
Last Update Posted : December 3, 2020
Sponsor:
Collaborator:
National Center for Research and Development, Poland
Information provided by (Responsible Party):
Polski Bank Komorek Macierzystych JSC (PBKM)

Brief Summary:
The objective of this study is to evaluate the safety of intrathecal administration of Wharton's Jelly Mesenchymal Stem Cells (WJMSC) and the impact on the immune system of patients with Amyotrophic Lateral Sclerosis.

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: Mesenchymal stem cells isolated from Wharton's jelly Phase 1 Phase 2

Detailed Description:

Clinical Phase: I/II

Population: Patients with Amyotrophic Lateral Sclerosis.

Project Design: One arm, non-blinded, open label study

Planned Sample Size: 20 patients

Investigational Medicinal Product: active IMP - mesenchymal stem cells isolated from Wharton's jelly

Screening:

Three visits on site to check the eligibility criteria (around 90, 60 and 30 days before first IMP administration)

Treatment (IMP administration):

Each patient will receive IMP three times: on baseline (day 0), 30 and 60 days after baseline (+/- 7 days).

Administration route: intrathecal

Follow up:

Duration: 18 months after first IMP administration Four on-site visits (3, 6, 9, 12 months after first IMP administration) and seven phone visits (4, 5, 7, 8, 10, 11 and 18 months after first IMP administration)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Evaluation of the Effect of Wharton's Jelly Mesenchymal Stem Cells (WJMSCs) on the Immune System of Patients With Amyotrophic Lateral Sclerosis (ALS)
Actual Study Start Date : December 2, 2020
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : February 2023


Arm Intervention/treatment
Experimental: Treatment arm
It is planned that IMP administration will be performed three times for each enrolled patient. IMP administration could be performed only if the patients does not have any contraindications for lumbar puncture.
Drug: Mesenchymal stem cells isolated from Wharton's jelly
Intrathecal administration of mesenchymal stem cells




Primary Outcome Measures :
  1. The number of (S)AESI [(Serious) Adverse Event of Special Interest] [ Time Frame: 3 month FU (follow-up) ]

    (S)AESI are defined as:

    1. Meningitis and encephalitis.
    2. Toxic encephalopathy.
    3. High fever >39⁰C.
    4. Epileptic seizures that are not connected to conditions above (meningitis, encephalitis, toxic encephalopathy, high fever).


Secondary Outcome Measures :
  1. Disease progression [ Time Frame: screening, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 18 month FU ]

    Disease progression assessed in ALSFRS-R scale (Revised Amyotrophic Lateral Sclerosis Functional Rating Scale). Higher scores mean a better outcome.

    Minimum: 0 points Maximum: 48 points


  2. Pulmonary function decline [ Time Frame: screening, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 6, 9 and 12 month FU. ]
    Pulmonary function decline assessed in spirometry (forced vital capacity)

  3. Muscle strength decline [ Time Frame: screening, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 6, 9 and 12 month FU ]
    Muscle strength decline assessed in physical examination

  4. Upper motor neuron function [ Time Frame: screening, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 6, 9 and 12 month FU ]
    Upper motor neuron function assessed in UMNS scale (Upper Motor Neuron Scale). Best outcome 16 points, worst outcomes: 0 points and 48 points Minimum: 0 points Maximum: 48 points

  5. Cognitive function [ Time Frame: screening and 12 month FU ]

    Cognitive function assessed in ECAS (The Edinburgh Cognitive and Behavioural ALS Screen). Higher scores mean a better outcome.

    Minimum: 0 points Maximum: 136 points


  6. Quality of life changes [ Time Frame: screening, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 18 month FU ]
    Quality of life changes, assessed by EQ-5D questionnaire - standardized instrument for measuring generic health status. Higher scores mean a better outcome.

  7. The change of defined cytokines, chemokines, growth factors, cystatin C and pNFH (phosphorylated neurofilament heavy chain) level in CSF (Cerebrospinal fluid) [ Time Frame: run-in visit (-60 day), at baseline and at 1, 2 and 6 month FU (12 month FU optional) ]
    The change of defined cytokines, chemokines, growth factors, cystatin C and pNFH level assessed in the samples of CSF

  8. The change of defined cytokines, chemokines and cystatin C level in blood [ Time Frame: screening visit, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 6, 9 and 12 month FU. ]
    The change of defined cytokines, chemokines and cystatin C level assessed in the samples of blood serum

  9. The change of creatinine and p75ECD level in urine [ Time Frame: screening visit, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 6, 9 and 12 month FU. ]
    The change of creatinine and p75ECD level

  10. Muscle function changes [ Time Frame: baseline and at 1, 2, 6 and 12 month FU ]
    Muscle function changes, assessed based on EMG examination (Electrophysiological examination of the muscle - MUNIX - motor unit number estimation)

  11. The change of the brain visualization [ Time Frame: run-in visit (-60 day), 6 and 12 month FU ]
    The change of the brain visualization in MRI (T1, T2 and DTI)

  12. SAE (Serious Adverse Event)/AE (Adverse Event) and (S)AESI [ Time Frame: 18 month FU ]
    The number of SAE/AE and (S)AESI - defined as in Outcome 1

  13. Survival period to disease progression [ Time Frame: 18 month FU ]

    The number of days from patients randomization to the end of the patients participation in the trial or to the one of the following:

    • PAV (permanent assisted ventilation)
    • Tracheostomy
    • Death

  14. Mortality rate [ Time Frame: 18 month FU ]
    Percentage of deaths in the entire study population.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult patients (at least 18 years old)
  2. The minimum patient's weight is not less than 40 kg
  3. Diagnosis of sporadic ALS, definite or probable, as defined by El Escorial World Federation of Neurology criteria
  4. History of ALS symptoms less than 2 years duration from the first symptoms of the disease
  5. More than 6 months from diagnosis of the disease
  6. Disease progression at 6 past months at least 3 points during this period of time
  7. ALSFRS-R scale of at least 30 at screening appointment
  8. Forced vital capacity >70% of predicted value for age, gender and height
  9. Treatment with stable dose of riluzole before baseline visit (for at least 1 month)
  10. Capable of providing written informed consent
  11. Able to comply with study requirements and willing to follow all study procedures and follow-up visits
  12. Women of child-bearing age and men with partners of child-bearing potential must agree to use two forms of contraceptive therapy throughout the course of the trial
  13. Women of child-bearing age must undergo pregnancy test
  14. Polish-language native speakers or patients who are proficient in the Polish language

Exclusion Criteria:

  1. Pregnancy or breastfeeding
  2. Tracheostomy
  3. Ventilator dependence
  4. Renal disease with creatinine >2mg/dl
  5. Liver disease with ALT, AST or GGTP 2-fold higher than upper normal limit
  6. Positive test for HBV, HCV, HIV with NAT method
  7. Positive tests for syphilis
  8. Any other clinically significant abnormalities on laboratory evaluation
  9. Any condition that would compromise ability of undergoing lumbar puncture
  10. Active systemic disease
  11. Autoimmune disease (Hashimoto disease under control is allowed)
  12. Uncontrolled diabetes
  13. Pulmonary disease that could affect interpretation of spirometry
  14. Neurological concomitant disease
  15. Unstable psychiatric concomitant disease
  16. High risk of suicide
  17. History of substance abuse within past year
  18. History of malignancy, within the previous 5 years, including melanoma with exception of localized skin cancers
  19. Any other clinically significant medical condition that can compromise patient's safety in the opinion of the investigator
  20. Treatment with immunomodulatory drugs (for example immunoglobulins, corticosteroids or other immunosuppressant) in last 6 months
  21. Participation in another clinical trial in last 6 months
  22. Previous cellular therapy of any kind
  23. Hypersensitivity to any component used in the cell culture
  24. Nuchal rigidity and other signs of meningitis
  25. Patients on chronic anticoagulation treatment (heparin/ warfarin/acenocoumarol/(N)OAC)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04651855


Contacts
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Contact: Natalia Żmijewska 0048-22-436-40-50 Natalia.Zmijewska@pbkm.pl

Locations
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Poland
JST sp. z o.o. Recruiting
Częstochowa, Poland, 42-202
Contact: Beata Świątkowska-Flis, MD, PhD       beatasflis@gmail.com   
Sponsors and Collaborators
Polski Bank Komorek Macierzystych JSC (PBKM)
National Center for Research and Development, Poland
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Responsible Party: Polski Bank Komorek Macierzystych JSC (PBKM)
ClinicalTrials.gov Identifier: NCT04651855    
Other Study ID Numbers: ALSTEM
First Posted: December 3, 2020    Key Record Dates
Last Update Posted: December 3, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Polski Bank Komorek Macierzystych JSC (PBKM):
Amyotrophic Lateral Sclerosis
Stem Cells
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases