Amyotrophic Lateral SclerosisPhase 1/2NCT04821479
Repeated Mesenchymal Stem Cell Injections in ALS
A Phase 1/2 study testing Mesenchymal stem cells (MSC) in people with Amyotrophic Lateral Sclerosis, run by Hadassah Medical Organization.
Trial summary
An open-label, single-center clinical trial to evaluate the safety and efficacy of repeated intrathecal administrations of autologous bone marrow derived mesenchyme stem cells in ALS patients. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Mesenchymal stem cells (MSC)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2016to 31 Dec 2020
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females ages 18 to 70 years old, at the Screening Visit.
- Sporadic or familial ALS diagnosed patients fulfilling the El Escorial clinical criteria for definite.
- Capable of providing informed consent and willing and able to follow study procedures, including willingness to undergo multiple/repeated lumbar punctures.
- ALSFRS-R ≥15 at the Screening Visit.
Who cannot join
- Patients with severe cognitive decline or inability to understand and sign the informed consent.
- Participation in another clinical trial within 1 year prior to start of the study
- Patients with active infections.
- Positive test for Hepatitis B, Hepatitis C, and/or HIV per laboratory evaluations at the screening visit.
- Any history of solid malignancy including any malignancy affecting the central nervous system within 5 years of the Screening Visit
About this study
Official title: Safety and Clinical Effects of Repeated Intrathecal Injections of Autologous Mesenchymal Stem Cells in Patients With Amyotrophic Lateral Sclerosis (ALS)
An open-label, single-center clinical trial to evaluate the safety and efficacy of repeated intrathecal administrations of autologous bone marrow derived mesenchyme stem cells in ALS patients. The study includes 20 subjects (age: 20-70) with definite diagnosis of ALS and ALS-FRS-R score of at least 20 and disease-duration of less than 3 years. The treatment protocol includes four intrathecal injections of MSC, at intervals of 3 months between the injections.
The primary endpoints are safety and tolerability. Several efficacy measures are assessed as secondary endpoints.
Read the detailed description
An open-label, single-center clinical trial to evaluate the safety and efficacy of repeated intrathecal administrations of autologous bone marrow derived mesenchyme stem cells in ALS patients. The study includes 20 subjects (age: 20-70) with definite diagnosis of ALS and ALS-FRS-R score of at least 20 and disease-duration of less than 3 years. The treatment protocol includes four intrathecal injections of MSC, at intervals of 3 months between the injections. The primary endpoints are safety and tolerability. Several efficacy measures are assessed as secondary endpoints.
Applications from patients are received in our centre. An independent selective committee set by hospital's administration examines anonymously, according to the predefined inclusion and exclusion criteria. After inclusion and screening visit, patients are followed up for a "run-in" period of 6 months before the first visit (visit 1), to evaluate the progression rate of their disease. and for six months following the last transplantation.
One month after inclusion, patients undergo bone Marrow Aspiration (BMA) procedure and MSC cells are produced from the bone marrow aspirate. On the treatment visit, the patients are transplanted with an intrathecal (IT) injection of MSC (1 million cells per kg of body weight) and thereafter with additional injections every 3-6 months. After the MSC transplantation patients are examined on a bimonthly basis and evaluated for ALSFRSr scoring and forced vital capacity of the lungs (FVC) for a total follow up period of 3 months post last MSC-injection.
To establish the progression rate of the disease the monthly changes in the functional ALS score: ALSFRSr will be calculated during the 6 months-"run in period" and for the whole duration of the study, ending at 3 months following the last injection of MSC stem cells. The progression rate (as evidenced by the monthly changes in ALSFRSr and FVC) during the study (calculated at last visit time point, 3 months after the last MSC-injection) will be compared to the progression rate during the "run-in" period.
The follow up visits include observation for side effects, full neurological evaluation and muscle chart, ALS score and forced vital capacity (FVC) test. The safety is assessed following treatment with MSC, using measurements of the following variables: physical examination, vital signs (HR, BP, RR, body temperature), and clinical laboratory parameters: WBC with differential and platelet count, hemoglobin (Hb), hematocrit (Ht), blood chemistry for electrolytes, creatinine and liver enzymes.
All selected patients undergo bone marrow aspiration under light general anaesthesia and an inoculum of crude bone marrow cells (150 ml) is obtained and two thirds of it kept frozen. One third is cultured under GCP conditions at the human cell cultures clean room facility of Hadassah HMO. The MSCs are obtained from the bone marrow of each patient and prepared using our previously described protocol with slight modification.
One month later the patient is hospitalized and a lumbar puncture performed under standard conditions and local anaesthesia at the L4-5 lumbar level and 3 ml of CSF are removed and the cultured purified MSCs (1x106/kg of body weight) resuspended in 3 ml of normal saline are injected in the CSF, using a 20-gauge needle and 3-way cannula.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Mesenchymal stem cells (MSC)
- Keywords
- ALS, Mesenchymal stem cells, ALSFRSr
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mesenchymal stem cells (MSC)Biological
Also called stem cells, Stromal cells
Intrathecal injections of autologous bone marrow derived mesenchymal stem cells
| Study group | Role | What they receive |
|---|---|---|
| Repeated MSCs treatment in ALS patients | Experimental | Four intrathecal (IT) administrations of autologous MSC cells administered every 3 months in ALS patients. the IT treatment will be administered through a regular lumbar puncture at a dose of 1x10^6 MSCs per kg body weight in 3 ml saline. Receives: Biological: Mesenchymal stem cells (MSC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of multiple intrathecal MSC administration. Incidence of adverse events following multiple intrathecal MSC injections during 2 years follow-up period
To evaluate the safety of 4 successive intrathecal administrations of autologous MSC cells administered every three months in ALS patient.
Patients will be follow-up every 3 months for change in their neurological status and the incidence of adverse events. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: Up to 18 months: starting from inclusion until 3 months after the last MSC-injection
Effect of repeated intrathecal MSC injections on the progression rate (monthly changes) of ALSFRSr
Degree of change in the rate of progression (calculation of monthly change in ALSFRSr score: 0-48, higher scores are better) between the run-in period to 3 months post last MSC-injection
Measured: Up to 18 months: starting from inclusion until 3 months after the last MSC-injection.
Secondary outcomes (1)
Effect of repeated intrathecal MSC injections on the progression rate (monthly changes) of respiratory forced vital capacity FVC
Degree of change in the rate of progression (calculation of monthly change in FVC score: 0-100%, higher numbers are better) between the run-in period to 3 months post last MSC-injection
Measured: Up to 18 months: starting from inclusion until 3 months after the last MSC-injection.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2021
- Study start1 Jan 2016
- Primary completion30 Jun 2020
- Study completion31 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single center open label study
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hadassah Medical Organization
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dimitrios Karussis, Professor, Principal investigator, Hadassah HMO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04821479
- Sponsor's protocol ID
- 0208-16-HMO
- Status last verified
- May 2020
- First submitted
- 19 Oct 2020
- Last updated
- 29 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Petrou P, Kassis I, Yaghmour NE, Ginzberg A, Karussis D. A phase II clinical trial with repeated intrathecal injections of autologous mesenchymal stem cells in patients with amyotrophic lateral sclerosis. Front Biosci (Landmark Ed). 2021 Oct 30;26(10):693-706. doi: 10.52586/4980.
PubMed 34719198
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Clinical Effects of Repeated Intrathecal Injections of Autologous Mesenchymal Stem Cells in Patients With Amyotrophic Lateral Sclerosis (ALS)
- ClinicalTrials.gov ID
- NCT04821479
- Acronym / sponsor ID
- 0208-16-HMO
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- ALS, Mesenchymal stem cells, ALSFRSr
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Hadassah Medical OrganizationUniversity, hospital or other
- Study start
- 1 Jan 2016 (actual)
- Primary completion
- 30 Jun 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 29 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An open-label, single-center clinical trial to evaluate the safety and efficacy of repeated intrathecal administrations of autologous bone marrow derived mesenchyme stem cells in ALS patients. The study includes 20 subjects (age: 20-70) with definite diagnosis of ALS and ALS-FRS-R score of at least 20 and disease-duration of less than 3 years. The treatment protocol includes four intrathecal injections of MSC, at intervals of 3 months between the injections.
The primary endpoints are safety and tolerability. Several efficacy measures are assessed as secondary endpoints.
Detailed description
An open-label, single-center clinical trial to evaluate the safety and efficacy of repeated intrathecal administrations of autologous bone marrow derived mesenchyme stem cells in ALS patients. The study includes 20 subjects (age: 20-70) with definite diagnosis of ALS and ALS-FRS-R score of at least 20 and disease-duration of less than 3 years. The treatment protocol includes four intrathecal injections of MSC, at intervals of 3 months between the injections. The primary endpoints are safety and tolerability. Several efficacy measures are assessed as secondary endpoints.
Applications from patients are received in our centre. An independent selective committee set by hospital's administration examines anonymously, according to the predefined inclusion and exclusion criteria. After inclusion and screening visit, patients are followed up for a "run-in" period of 6 months before the first visit (visit 1), to evaluate the progression rate of their disease. and for six months following the last transplantation.
One month after inclusion, patients undergo bone Marrow Aspiration (BMA) procedure and MSC cells are produced from the bone marrow aspirate. On the treatment visit, the patients are transplanted with an intrathecal (IT) injection of MSC (1 million cells per kg of body weight) and thereafter with additional injections every 3-6 months. After the MSC transplantation patients are examined on a bimonthly basis and evaluated for ALSFRSr scoring and forced vital capacity of the lungs (FVC) for a total follow up period of 3 months post last MSC-injection.
To establish the progression rate of the disease the monthly changes in the functional ALS score: ALSFRSr will be calculated during the 6 months-"run in period" and for the whole duration of the study, ending at 3 months following the last injection of MSC stem cells. The progression rate (as evidenced by the monthly changes in ALSFRSr and FVC) during the study (calculated at last visit time point, 3 months after the last MSC-injection) will be compared to the progression rate during the "run-in" period.
The follow up visits include observation for side effects, full neurological evaluation and muscle chart, ALS score and forced vital capacity (FVC) test. The safety is assessed following treatment with MSC, using measurements of the following variables: physical examination, vital signs (HR, BP, RR, body temperature), and clinical laboratory parameters: WBC with differential and platelet count, hemoglobin (Hb), hematocrit (Ht), blood chemistry for electrolytes, creatinine and liver enzymes.
All selected patients undergo bone marrow aspiration under light general anaesthesia and an inoculum of crude bone marrow cells (150 ml) is obtained and two thirds of it kept frozen. One third is cultured under GCP conditions at the human cell cultures clean room facility of Hadassah HMO. The MSCs are obtained from the bone marrow of each patient and prepared using our previously described protocol with slight modification.
One month later the patient is hospitalized and a lumbar puncture performed under standard conditions and local anaesthesia at the L4-5 lumbar level and 3 ml of CSF are removed and the cultured purified MSCs (1x106/kg of body weight) resuspended in 3 ml of normal saline are injected in the CSF, using a 20-gauge needle and 3-way cannula.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single center open label study
| Arm | Type | Receives |
|---|---|---|
| Repeated MSCs treatment in ALS patients | Experimental | Biological: Mesenchymal stem cells (MSC)Four intrathecal (IT) administrations of autologous MSC cells administered every 3 months in ALS patients. the IT treatment will be administered through a regular lumbar puncture at a dose of 1x10^6 MSCs per kg body weight in 3 ml saline. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Males and females ages 18 to 70 years old, at the Screening Visit.
- Sporadic or familial ALS diagnosed patients fulfilling the El Escorial clinical criteria for definite.
- Capable of providing informed consent and willing and able to follow study procedures, including willingness to undergo multiple/repeated lumbar punctures.
- ALSFRS-R ≥15 at the Screening Visit.
Key exclusion criteria (5 listed)
- Patients with severe cognitive decline or inability to understand and sign the informed consent.
- Participation in another clinical trial within 1 year prior to start of the study
- Patients with active infections.
- Positive test for Hepatitis B, Hepatitis C, and/or HIV per laboratory evaluations at the screening visit.
- Any history of solid malignancy including any malignancy affecting the central nervous system within 5 years of the Screening Visit
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mesenchymal stem cells (MSC)Also: stem cells, Stromal cellsIntrathecal injections of autologous bone marrow derived mesenchymal stem cells | Biological | Repeated MSCs treatment in ALS patients |
Primary outcome
Safety of multiple intrathecal MSC administration. Incidence of adverse events following multiple intrathecal MSC injections during 2 years follow-up period
Time frame: Up to 18 months: starting from inclusion until 3 months after the last MSC-injection
To evaluate the safety of 4 successive intrathecal administrations of autologous MSC cells administered every three months in ALS patient. Patients will be follow-up every 3 months for change in their neurological status and the incidence of adverse events. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Effect of repeated intrathecal MSC injections on the progression rate (monthly changes) of ALSFRSr
Time frame: Up to 18 months: starting from inclusion until 3 months after the last MSC-injection.
Degree of change in the rate of progression (calculation of monthly change in ALSFRSr score: 0-48, higher scores are better) between the run-in period to 3 months post last MSC-injection
1 secondary outcome
Effect of repeated intrathecal MSC injections on the progression rate (monthly changes) of respiratory forced vital capacity FVC
Time frame: Up to 18 months: starting from inclusion until 3 months after the last MSC-injection.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2021.
- Derived from this study: PubMed 34719198Petrou P, Kassis I, Yaghmour NE, Ginzberg A, Karussis D. A phase II clinical trial with repeated intrathecal injections of autologous mesenchymal stem cells in patients with amyotrophic lateral sclerosis. Front Biosci (Landmark Ed). 2021 Oct 30;26(10):693-706. doi: 10.52586/4980.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dimitrios Karussis, Professor principal investigator
Hadassah HMO
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Mesenchymal stem cells (MSC) in people with Amyotrophic Lateral Sclerosis, run by Hadassah Medical Organization.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of multiple intrathecal MSC administration. Incidence of adverse events following multiple intrathecal MSC injections during 2 years follow-up period (time frame: Up to 18 months: starting from inclusion until 3 months after the last MSC-injection). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04821479, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2021.