Dose Escalation and Safety Study of Human Spinal Cord Derived Neural Stem Cell Transplantation for the Treatment of Amyotrophic Lateral Sclerosis

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
Neuralstem Inc.
ClinicalTrials.gov Identifier:
NCT01730716
First received: November 6, 2012
Last updated: June 4, 2014
Last verified: May 2013
  Purpose

The study is to determine the feasibility, safety, toxicity, and maximum tolerated (safe) dose of human spinal derived neural stem cell transplantation for the treatment of Amyotrophic Lateral Sclerosis (ALS).


Condition Intervention Phase
Amyotrophic Lateral Sclerosis
Device: Human spinal cord stem cell implantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Open-label, Dose Escalation and Safety Study of Human Spinal Cord Derived Neural Stem Cell Transplantation for the Treatment of Amyotrophic Lateral Sclerosis

Resource links provided by NLM:


Further study details as provided by Neuralstem Inc.:

Primary Outcome Measures:
  • To determine the safety of the maximum tolerated dose of human spinal cord-derived neural stem cell transplantation for the treatment of amyotrophic lateral sclerosis (ALS) assessed by the number and severity of adverse events. [ Time Frame: Patients will be followed postoperatively for 24 months. ] [ Designated as safety issue: Yes ]
    The primary objective of the study is to determine the feasibility, safety, toxicity, and maximum tolerated (safe) dose of human spinal cord-derived neural stem cell transplantation for the treatment of amyotrophic lateral sclerosis (ALS).


Secondary Outcome Measures:
  • To evaluate neurologic deficits post spinal stem cell transplantation therapy. [ Time Frame: Patients will be followed postoperatively for 24 months. ] [ Designated as safety issue: Yes ]
    The secondary objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population for: 1) attenuation of motor function loss; 2) maintenance of respiratory capacity; 3) stabilization of ALSFRS-R; 4) reduction of spasticity/rigidity if present; and 5) graft survival at autopsy if and when there is mortality.


Estimated Enrollment: 18
Study Start Date: May 2013
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Surgery
There will be 5 sequential cohorts (Groups A-E) with 3 subjects in each cohort. Each cohort will follow a dose escalation plan. New patients will be enrolled into each group. No control group is included. All patients will received spinal cord injections of HSSC.
Device: Human spinal cord stem cell implantation
Human spinal cord stem cell implantation in ALS patients.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Have the ability to understand the requirements of the study, provide written informed consent, understand and provide written authorization for the use and disclosure of Protected Health Information (PHI) [per Health Insurance Portability and Accountability Act (HIPAA) Privacy Ruling] and comply with the study procedures.
  2. Subjects with sporadic or familial ALS, meeting the definition of laboratory-supported probable, probable or definite ALS according to the World Federation of Neurology El Escorial Criteria (Appendix A). At the time of enrollment subjects should be within 24 months of symptom onset.
  3. Age 18 years or older.
  4. Females must have a negative serum pregnancy test and practice an acceptable method of contraception or be of non-childbearing potential (post-menopausal for at least 2 years or surgically sterile [hysterectomy, oophorectomy or surgical sterilization]).
  5. Geographic accessibility to the study center and the ability to travel to the clinic for study visits.
  6. Presence of a willing and able caregiver.
  7. Medically able to undergo lumbar and/or cervical laminectomy or laminoplasty as determined by the site Principal Investigator and neurosurgeon.
  8. Medically able to tolerate the immunosuppression regimen consisting of basiliximab, tacrolimus, mycophenolate mofetil, prednisone and methylprednisolone as determined by the site PI.
  9. Agrees to the visit schedule as outlined in the informed consent.
  10. Not taking riluzole (Rilutek®) or on a stable dose for ≥ 30 days.
  11. Vital capacity ≥ 60% of predicted normal for age, height and gender measured in the seated position and ≥50% in supine position during the 7 days prior to surgery.
  12. Ambulatory subjects with extremity weakness and/or spasticity due to ALS. Patients undergoing lumbar surgery must have demonstrable weakness or spasticity in one or both lower extremities. Patients undergoing cervical surgery must have demonstrable weakness or spasticity in one or both upper extremities, with at least antigravity strength. Subjects must have normal neck extensor and flexor strength.

Exclusion Criteria:

  1. Etiology of paraplegia or weakness is due to causes other than ALS.
  2. A positive result on the Panel Reactive Antibody (PRA) test, with the presence of specific HLA antibodies matching the HLA DNA profile of the donor cells.
  3. Any known immunodeficiency syndrome.
  4. Receipt of any investigational drug, device or biologic within 30 days of surgery.
  5. Any concomitant medical disease or condition limiting the safety to participate:

    1. Coagulopathy
    2. Active uncontrolled infection
    3. Hypotension requiring vasopressor therapy
    4. Previous spinal surgery that the neurosurgeon deems to be an obstacle to the planned transplantation
    5. Skin breakdown over the site of surgery
    6. Malignancy (except for non-melanoma skin cancer)
    7. Spinal stenosis severe enough to preclude surgery (as determined by the neurosurgeon)
    8. Pre-existing kyphosis by preoperative MRI or X-ray
    9. Less than 5/5 grade in neck extension and strength test at the time of surgery.
  6. Creatinine >1.5, liver function tests (SGOT/SGPT, Bilirubin, Alk Phos) > 2x upper limit of normal, hematocrit/hemoglobin < 30/10, total WBC < 4000, uncontrolled hypertension (systolic > 180 or diastolic > 100) or uncontrolled diabetes (defined as hemoglobin A1C >8), evidence of GI bleeding by hemoccult test, tuberculosis (TB test: PPD), serologic evidence of current infection with a hepatitis virus or human immunodeficiency virus (HIV).
  7. Presence of any of the following conditions:

    1. Current drug abuse or alcoholism
    2. Unstable medical conditions
    3. Unstable psychiatric illness including psychosis and untreated major depression within 90 days of screening
  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.
  9. Any condition that the neurosurgeon feels may pose complications for the surgery.
  10. Known hypersensitivity to basiliximab, tacrolimus, mycophenolate mofetil, prednisone or methylprednisolone.
  11. Inability to provide informed consent as determined by the site PI.
  12. Inadequate family or caregiver support as determined by the site PI.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01730716

Locations
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
Neuralstem Inc.
  More Information

Additional Information:
Publications:
Responsible Party: Neuralstem Inc.
ClinicalTrials.gov Identifier: NCT01730716     History of Changes
Other Study ID Numbers: NS2012-3
Study First Received: November 6, 2012
Last Updated: June 4, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Neuralstem Inc.:
Human spinal cord derived neural stem cell transplantation
ALS

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

ClinicalTrials.gov processed this record on August 01, 2014