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CNS10-NPC-GDNF for the Treatment of ALS

This study is currently recruiting participants.
Verified August 2017 by Robert H. Baloh, Cedars-Sinai Medical Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT02943850
First Posted: October 25, 2016
Last Update Posted: August 3, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
California Institute for Regenerative Medicine
Information provided by (Responsible Party):
Robert H. Baloh, Cedars-Sinai Medical Center
  Purpose
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.

Condition Intervention Phase
Amyotrophic Lateral Sclerosis Biological: Stem cell (HPC) implantation Device: Stereotactic surgical device Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Human Neural Progenitor Cells Secreting Glial Cell Line-Derived Neurotrophic Factor (CNS10-NPC-GDNF) for the Treatment of Amyotrophic Lateral Sclerosis

Resource links provided by NLM:


Further study details as provided by Robert H. Baloh, Cedars-Sinai Medical Center:

Primary Outcome Measures:
  • 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)


Secondary Outcome Measures:
  • Compound Motor Action Potential (CMAP) [ Time Frame: CMAP will be performed 7 times over 15 months ]
    Compound Motor Action Potential - CMAP (Tibialis anterior)

  • Force Generation via ATLIS testing [ Time Frame: ATLIS testing will be performed 7 times over 15 months ]
    Lower extremity Force Generation via ATLIS testing

  • Quantitative Muscle MRI [ Time Frame: Muscle MRI will be performed 6 times over 15 months ]
    Quantitative Muscle MRI of bilateral lower extremities

  • Electrical Impedance Myography (EIM) [ Time Frame: EIM will be performed 7 times over 15 months ]
    Lower Extremity Electrical Impedance Myography (EIM)

  • 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 ]
    Assessment of GDNF in the CSF


Estimated Enrollment: 18
Actual Study Start Date: April 1, 2017
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: April 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Stem cell implantation
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.
Biological: Stem cell (HPC) implantation
All patients will received unilateral lumbar spinal cord injections of CNS10-NPC-GDNF cells.
Device: Stereotactic surgical device
A newly developed stereotactic frame is being evaluated as a part of this trial

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)
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  1. Confirmed diagnosis of ALS (Lab-supported Probable, Probable or Definite EI Escorial Criteria)
  2. Duration of symptoms ≤ 36 months
  3. Progressive weakness in lower extremities, with EMG supported evidence of denervation in both lower extremities.
  4. Forced Vital Capacity >60% of predicted normal in supine.
  5. Male/Female; Age: 18 and older
  6. Able to provide Informed Consent
  7. Be geographically accessible to the study site and able to travel to study site for required visits
  8. Have caregiver to assist in the transportation and care required by participation in the study
  9. Not taking riluzole or on a stable dose for ≥ 30 days
  10. For women of child bearing capacity, negative pregnancy test prior to surgery
  11. Medically able to undergo thoracolumbar laminectomy or laminoplasty as determined by the site PI and Neurosurgeon
  12. Medically able to tolerate the immunosuppression regimen as determined by the site PI

Exclusion Criteria:

  1. Using invasive ventilatory assistance
  2. Diagnosis of another active or unstable medical illness that may interfere with study participation at discretion of PI
  3. Presence of any of the following conditions:

    1. Current drug or alcohol abuse
    2. Any known immunodeficiency syndrome
    3. Unstable medical condition
    4. Unstable psychiatric illness including psychosis and untreated major depression within 90 days of screening
  4. Persons of child bearing capacity not willing to practice birth control
  5. Receiving any investigational device/biologic/drug in past 30 days or any previous exposure to stem cell therapy
  6. Any condition in the lower extremities which precludes serial strength testing
  7. Any condition that the Neurosurgeon feels may pose complications for the surgery
  8. 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
  Contacts and Locations
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): NCT02943850


Contacts
Contact: Peggy Allred 310-423-1791 MNDresearchcenter@cshs.org

Locations
United States, California
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Peggy Allred    310-423-1791      
Sponsors and Collaborators
Cedars-Sinai Medical Center
California Institute for Regenerative Medicine
Investigators
Principal Investigator: Robert H. Baloh, MD, PhD Cedars-Sinai Medical Center
  More Information

Responsible Party: Robert H. Baloh, Director of Neuromuscular Medicine, ALS Program Director, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier: NCT02943850     History of Changes
Other Study ID Numbers: Pro00042350
First Submitted: October 20, 2016
First Posted: October 25, 2016
Last Update Posted: August 3, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No

Keywords provided by Robert H. Baloh, Cedars-Sinai Medical Center:
stem cells
growth factor
ALS

Additional relevant MeSH terms:
Sclerosis
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases