Amyotrophic Lateral SclerosisPhase 1NCT02943850

CNS10-NPC-GDNF for the Treatment of ALS

A Phase 1 study testing Stem cell (HPC) implantation and Stereotactic surgical device in people with Amyotrophic Lateral Sclerosis, run by Cedars-Sinai Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Amyotrophic Lateral Sclerosis
What is being tested?: Stem cell (HPC) implantation and Stereotactic surgical device
Type of treatment: Injection or infusion, Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 1 siteUnited States
Study dates: 1 Apr 2017to 18 Oct 2019
Phase: Phase 1
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Confirmed diagnosis of ALS (Lab-supported Probable, Probable or Definite EI Escorial Criteria)
Duration of symptoms ≤ 36 months
Progressive weakness in lower extremities, with EMG supported evidence of denervation in both lower extremities.
Forced Vital Capacity >60% of predicted normal in supine.
Male/Female; Age: 18 and older
Able to provide Informed Consent

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Be geographically accessible to the study site and able to travel to study site for required visits
Have caregiver to assist in the transportation and care required by participation in the study
Not taking riluzole or on a stable dose for ≥ 30 days
For women of child bearing capacity, negative pregnancy test prior to surgery
Medically able to undergo thoracolumbar laminectomy or laminoplasty as determined by the site PI and Neurosurgeon
Medically able to tolerate the immunosuppression regimen as determined by the site PI

Who cannot join

Using invasive ventilatory assistance
Diagnosis of another active or unstable medical illness that may interfere with study participation at discretion of PI
Presence of any of the following conditions:
Current drug or alcohol abuse
Any known immunodeficiency syndrome
Unstable medical condition

Show all 12Show fewer

Unstable psychiatric illness including psychosis and untreated major depression within 90 days of screening
Persons of child bearing capacity not willing to practice birth control
Receiving any investigational device/biologic/drug in past 30 days or any previous exposure to stem cell therapy
Any condition in the lower extremities which precludes serial strength testing
Any condition that the Neurosurgeon feels may pose complications for the surgery
Any condition or ALS disease phenotype that the site PI feels may interfere with participation in the study or in the interpretation of study endpoints

Trial locations and contacts

1 site in 1 country.

United States1 site

Cedars-Sinai Medical Center
Los Angeles, California, 90048

Other trials in United States

About this study

Official title: Human Neural Progenitor Cells Secreting Glial Cell Line-Derived Neurotrophic Factor (CNS10-NPC-GDNF) for the Treatment of Amyotrophic Lateral Sclerosis

The investigator is examining the safety of transplanting cells that have been engineered to produce a growth factor into the spinal cord of patients with Amyotrophic Lateral Sclerosis (ALS). The cells are called neural progenitor cells, which are a type of stem cell that can become several different types of cells in the nervous system. These cells have been derived to specifically become astrocytes, which is a type of neuronal cell. The growth factor is called glial cell line-derived neurotrophic factor, or GDNF. GDNF is a protein that promotes the survival of many types of neuronal cells. Therefore, the cells are called "CNS10-NPC-GDNF." The investigational treatment has been tested in animals, but it has not yet been tested in people. In this study, we want to learn if CNS10-NPC-GDNF cells are safe to transplant into the spinal cords of people.

Read the detailed description

This study will be the first to use a genetically modified progenitor cells to treat a neurodegenerative disease. This is a Phase 1/2a, single-center, blinded (as to side of injection), safety study of two escalating doses of human neural progenitor cells expressing GDNF (CNS10-NPC-GDNF) delivered unilaterally to the lumbar region in ALS subjects with moderate leg involvement.

Subjects meeting all Eligibility Criteria and providing Informed Consent will be enrolled in one of two sequential dosing groups. Subjects will be treated sequentially with a minimum of one month interval between surgeries for the first three subjects in each dosing cohort. The remaining subjects in the cohort will be treated with a minimum interval of at least two weeks between surgeries.

Specific aims:

Safety, as evaluated by:

Adverse Events and Serious Adverse Events
Clinical laboratory assessments, as clinically indicated (hematology, chemistry, immunology)

Conditions: Amyotrophic Lateral Sclerosis
Being tested: Stem cell (HPC) implantation, Stereotactic surgical device
Keywords: stem cells, growth factor, ALS
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.

Stem cell (HPC) implantationBiological
All patients will received unilateral lumbar spinal cord injections of CNS10-NPC-GDNF cells.
Stereotactic surgical deviceDevice
A newly developed stereotactic frame is being evaluated as a part of this trial

Study groups in NCT02943850
Study group	Role	What they receive
Stem cell implantation	Experimental	Subjects meeting all Eligibility Criteria and providing Informed Consent will be enrolled in one of two sequential dosing groups (Group A and B). Subjects will be treated sequentially with a minimum of one month interval between surgeries for the first three subjects in each dosing cohort. The remaining subjects in the cohort will be treated with a minimum interval of at least one week between surgeries. There will be 9 subjects in each group. No control group is included. All patients will received unilateral lumbar spinal cord injections of CNS10-NPC-GDNF cells. Receives: Biological: Stem cell (HPC) implantation; Device: Stereotactic surgical device

What is being measured

The primary outcome is the main question the study is designed to answer.

Safety evaluated by Adverse Events and Serious Adverse Events, post-operative MRI, and clinical laboratory assessments
Safety, as evaluated by:
- Adverse Events and Serious Adverse Events
- Post-op MRI
- Clinical laboratory assessments, as clinically indicated (hematology, chemistry, immunology)
Measured: Patients will be followed postoperatively for 12 months

Secondary outcomes (5)

Compound Motor Action Potential (CMAP)
Compound Motor Action Potential - CMAP (Tibialis anterior)
Measured: CMAP will be performed 7 times over 15 months
Force Generation via ATLIS testing
Lower extremity Force Generation via ATLIS testing
Measured: ATLIS testing will be performed 7 times over 15 months
Quantitative Muscle MRI
Quantitative Muscle MRI of bilateral lower extremities
Measured: Muscle MRI will be performed 6 times over 15 months
Electrical Impedance Myography (EIM)
Lower Extremity Electrical Impedance Myography (EIM)
Measured: EIM will be performed 7 times over 15 months
Assessment of glial cell line derived neurotrophic factor (GDNF) in the cerebral spianl fluid (CSF)
Assessment of GDNF in the CSF
Measured: CSF will be collected at 3 time points over 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Apr 201718 Oct 2019

First posted25 Oct 2016 (estimated)
Study start1 Apr 2017
Primary completion18 Oct 2019
Study completion18 Oct 2019

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.
More trials run by Cedars-Sinai Medical CenterThe sponsor's other registered studies.
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
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02943850
Sponsor's protocol ID: Pro00042350
Status last verified: Jul 2020
First submitted: 20 Oct 2016
Last updated: 15 Jul 2020
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: Yes
Individual data sharing: No

Publications

Baloh RH, Johnson JP, Avalos P, Allred P, Svendsen S, Gowing G, Roxas K, Wu A, Donahue B, Osborne S, Lawless G, Shelley B, Wheeler K, Prina C, Fine D, Kendra-Romito T, Stokes H, Manoukian V, Muthukumaran A, Garcia L, Banuelos MG, Godoy M, Bresee C, Yu H, Drazin D, Ross L, Naruse R, Babu H, Macklin EA, Vo A, Elsayegh A, Tourtellotte W, Maya M, Burford M, Diaz F, Patil CG, Lewis RA, Svendsen CN. Transplantation of human neural progenitor cells secreting GDNF into the spinal cord of patients with ALS: a phase 1/2a trial. Nat Med. 2022 Sep;28(9):1813-1822. doi: 10.1038/s41591-022-01956-3. Epub 2022 Sep 5.
PubMed 36064599

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Amyotrophic Lateral Sclerosis trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Human Neural Progenitor Cells Secreting Glial Cell Line-Derived Neurotrophic Factor (CNS10-NPC-GDNF) for the Treatment of Amyotrophic Lateral Sclerosis
ClinicalTrials.gov ID: NCT02943850
Acronym / sponsor ID: Pro00042350
Conditions: Amyotrophic Lateral Sclerosis
Keywords: stem cells, growth factor, ALS
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 18 participants (actual)
Lead sponsor: Cedars-Sinai Medical CenterUniversity, hospital or other
Collaborators: California Institute for Regenerative Medicine (CIRM)
Study start: 1 Apr 2017 (actual)
Primary completion: 18 Oct 2019 (actual)
Study completion: 18 Oct 2019 (actual)
First posted: 25 Oct 2016 (estimated)
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.

Detailed description

Specific aims:

Safety, as evaluated by:

Adverse Events and Serious Adverse Events
Clinical laboratory assessments, as clinically indicated (hematology, chemistry, immunology)

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Stem cell implantation	Experimental	Biological: Stem cell (HPC) implantation, Device: Stereotactic surgical deviceSubjects meeting all Eligibility Criteria and providing Informed Consent will be enrolled in one of two sequential dosing groups (Group A and B). Subjects will be treated sequentially with a minimum of one month interval between surgeries for the first three subjects in each dosing cohort. The remaining subjects in the cohort will be treated with a minimum interval of at least one week between surgeries. There will be 9 subjects in each group. No control group is included. All patients will received unilateral lumbar spinal cord injections of CNS10-NPC-GDNF cells.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

Confirmed diagnosis of ALS (Lab-supported Probable, Probable or Definite EI Escorial Criteria)
Duration of symptoms ≤ 36 months
Progressive weakness in lower extremities, with EMG supported evidence of denervation in both lower extremities.
Forced Vital Capacity >60% of predicted normal in supine.
Male/Female; Age: 18 and older

Key exclusion criteria (12 listed)

Using invasive ventilatory assistance
Diagnosis of another active or unstable medical illness that may interfere with study participation at discretion of PI
Presence of any of the following conditions:
Persons of child bearing capacity not willing to practice birth control
Receiving any investigational device/biologic/drug in past 30 days or any previous exposure to stem cell therapy

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
Stem cell (HPC) implantationAll patients will received unilateral lumbar spinal cord injections of CNS10-NPC-GDNF cells.	Biological	Stem cell implantation
Stereotactic surgical deviceA newly developed stereotactic frame is being evaluated as a part of this trial	Device	Stem cell implantation

Primary outcome

Safety evaluated by Adverse Events and Serious Adverse Events, post-operative MRI, and clinical laboratory assessments
Time frame: Patients will be followed postoperatively for 12 months
Safety, as evaluated by: * Adverse Events and Serious Adverse Events * Post-op MRI * Clinical laboratory assessments, as clinically indicated (hematology, chemistry, immunology)

5 secondary outcomes

Compound Motor Action Potential (CMAP)
Time frame: CMAP will be performed 7 times over 15 months
Force Generation via ATLIS testing
Time frame: ATLIS testing will be performed 7 times over 15 months
Quantitative Muscle MRI
Time frame: Muscle MRI will be performed 6 times over 15 months
Electrical Impedance Myography (EIM)
Time frame: EIM will be performed 7 times over 15 months
Assessment of glial cell line derived neurotrophic factor (GDNF) in the cerebral spianl fluid (CSF)
Time frame: CSF will be collected at 3 time points over 12 months

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 15 Jul 2020.
Derived from this study: PubMed 36064599Baloh RH, Johnson JP, Avalos P, Allred P, Svendsen S, Gowing G, Roxas K, Wu A, Donahue B, Osborne S, Lawless G, Shelley B, Wheeler K, Prina C, Fine D, Kendra-Romito T, Stokes H, Manoukian V, Muthukumaran A, Garcia L, Banuelos MG, Godoy M, Bresee C, Yu H, Drazin D, Ross L, Naruse R, Babu H, Macklin EA, Vo A, Elsayegh A, Tourtellotte W, Maya M, Burford M, Diaz F, Patil CG, Lewis RA, Svendsen CN. Transplantation of human neural progenitor cells secreting GDNF into the spinal cord of patients with ALS: a phase 1/2a trial. Nat Med. 2022 Sep;28(9):1813-1822. doi: 10.1038/s41591-022-01956-3. Epub 2022 Sep 5.
Individual participant dataSharing planned: No

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Amyotrophic Lateral Sclerosis (ALS), Bacillus Coagulans
Active, not recruiting
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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.

Robert H. Baloh, MD, PhD principal investigator

Cedars-Sinai Medical Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Stem cell (HPC) implantation and Stereotactic surgical device in people with Amyotrophic Lateral Sclerosis, run by Cedars-Sinai Medical Center at 1 site in United States.

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 12 inclusion and 12 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 15 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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 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.

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 evaluated by Adverse Events and Serious Adverse Events, post-operative MRI, and clinical laboratory assessments (time frame: Patients will be followed postoperatively for 12 months). 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 NCT02943850, 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 15 Jul 2020.