Human Spinal Cord Derived Neural Stem Cell Transplantation for the Treatment of Amyotrophic Lateral Sclerosis (ALS)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Neuralstem Inc.
ClinicalTrials.gov Identifier:
NCT01348451
First received: April 28, 2011
Last updated: January 3, 2014
Last verified: May 2013
  Purpose

This is a first-in-human trial of spinal derived stem cells transplanted into the spinal cord of patients with Amyotrophic Lateral Sclerosis (ALS). The goal of the study is to see if the cells and the procedure to transplant them are safe.


Condition Intervention Phase
Amyotrophic Lateral Sclerosis
Device: surgical implantation
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase l, Open-label, First in Human, Feasibility 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:
  • The primary objective of this study is to determine the safety of human spinal cord-derived neural stem cell transplantation for the treatment of amyotrophic lateral sclerosis. [ Time Frame: The primary outcome measure will be assessed at study visits pre and post surgery follow-up visits, for a total of 48 months. ] [ Designated as safety issue: Yes ]
    The primary outcome measure is the incidence of adverse events in the study population.


Secondary Outcome Measures:
  • The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population. [ Time Frame: The ALSFRS-R will be administered at -3, -2 and -1 months screening/presurgery, and at 1, 3, 6, 9, 12, 18, 24, 30, 36, 42 and 48 month follow-up/post surgery visits. ] [ Designated as safety issue: Yes ]
    The Secondary Outcome Measures of the study are to evaluate spinal stem cell transplantation therapy in this patient population using the following 11 assessments. 1. ALSFRS-R is a self-administered ordinal rating scale questionnaire (rating 0-4 for each question, 4 is most functional, 0-48 total) of 12 functional activities. The most functional total score is 48.

  • The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population. [ Time Frame: The quantitative muscle strength test will be administered at -3, -2, -1 months screening/presurgery and at 1, 3, 6, 9, 12, 18, 24, 30, 36, 42 and 48 month follow-up/post surgery visits. ] [ Designated as safety issue: Yes ]
    2. Quantitative muscle strength testing using a hand held dynamometer (HHD): Six proximal muscle groups (knee flexion and extension, hip flexion, elbow flexion and extension and shoulder flexion) and three proximal muscle groups (wrist extension, first dorsal interosseous contraction, and ankle dorsiflexion) will be tested bilaterally using the MICROFET 2 HHD.

  • The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population. [ Time Frame: The hand grip (bilateral) will be administered at -3, -2 and -1 months screening/presurgery, and at 1, 3, 6, 9, 12, 18, 24, 30, 36, 42 and 48 month follow-up/post surgery visits. ] [ Designated as safety issue: Yes ]
    3. Hand grip (bilateral) will be measured using the Jaymar Grip dynamometer.

  • The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population. [ Time Frame: The vital capacity (VC) will be measured at -3, -2 and -1 months and -7 days screening/presurgery. It will also be measured at 1, 2, 3, 6, 9, 12, 18, 24, 30, 36, 42 and 48 month follow-up/post surgery visits. ] [ Designated as safety issue: Yes ]
    4. Vital Capacity (VC) will be measured using the Renaissance II spirometer. Eligibility will be determined with seated and supine measurements but the secondary outcome measure will be done seated.

  • The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population. [ Time Frame: The negative inspiratory force (NIF) will be measured at -3, -2 and -1 months and -7 days screening/presurgery. It will also be measured at 1, 2, 3, 6, 9, 12, 18, 24, 30, 36, 42 and 48 month follow-up/post surgery visits. ] [ Designated as safety issue: Yes ]
    5. Negative Inspiratory Force (NIF) will be measured with a Negative Inspiratory Force Gauge (Instrumentation Industries).

  • The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population. [ Time Frame: The Electrical Impedance Myography (EIM) will be measured at -3, -2 and -1 months screening/presurgery. It will also be measured at 1, 3, 6, 9, 12, 18, 24, 30, 36, 42 and 48 month follow-up/post surgery visits. ] [ Designated as safety issue: Yes ]
    6. Electrical Impedance Myography (EIM) is a painless and non-invasive quantitative measure of muscle that has been shown to correlate with other physiological and semi-quantitative measures of disease progression in ALS .

  • The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population. [ Time Frame: The comprehensive pain assessment will be performed at -3 months and -14 days screening/presurgery. It will also be performed at 2 weeks, 1, 2, 3, 6, 9, 12, 18, 24, 30, 36, 42 and 48 month follow-up/post surgery visits. ] [ Designated as safety issue: Yes ]
    7. Comprehensive pain assessment utilizing the Neuropathic Pain Scale (NPS).

  • The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population. [ Time Frame: Performed during the screening and at 24 and 48 month follow-up/post surgery visits. MRI of the surgical region only, at 1, 6, 12, 18 and 36 month follow-up/post surgery visits. ] [ Designated as safety issue: Yes ]
    8. An MRI will be performed on the entire spine and brain with and without gadolinium contrast. An MRI of the targeted region may be performed if clinically indicated at the 2 week visit.

  • The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population. [ Time Frame: Measurements will be taken at -3 months and -14 days at screening/presurgery and at 1, 6, 9, 12, 18, 24, 30, 36, 42 and 48 month follow-up/post surgery visits. ] [ Designated as safety issue: Yes ]
    9. Urodynamic parameters including incontinence and urinary retention measured by post void residual.

  • The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population. [ Time Frame: The questionnaire will be completed at -3 months during the screening/presurgery phase and at the 3, 6, 9, 12, 18, 24, 30, 36, 42 and 48 month follow-up/post surgery visits. ] [ Designated as safety issue: Yes ]
    10. ALS Specific Quality of Life Questionnaire - Revised is a scale that balances physical and nonphysical factors in assessing the quality of life in ALS patients

  • The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population. [ Time Frame: The Ashworth Spasticity Scale will be administered at -3, -2, -1 months screening/presurgery and at 1, 3, 6, 9, 12, 18, 24, 30, 36, 42 and 48 month follow-up/post surgery visits. ] [ Designated as safety issue: Yes ]
    11. Ashworth Spasticity Scale.


Estimated Enrollment: 18
Study Start Date: January 2009
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: surgery
A sequential design of five groups will be utilized to reduce risk to subjects. The first group (Group A) will include six subjects and the subsequent groups will include three subjects per group. Each group represents both different inclusion criteria and location of surgery.
Device: surgical 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 diagnosed as laboratory-supported probable,probable or definite according to the World Federation of Neurology El Escorial Criteria (Appendix A), based on examination by the site PI.
  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 or cervical laminectomy as determined by the Investigator, surgeon and anesthesiologist.
  8. Medically able to tolerate immunosuppression regimen consisting of basiliximab, tacrolimus, mycophenolate mofetil, and methylprednisolone as determined by the site Investigator.
  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. All required vaccinations current: tetanus/diptheria (TDAP), herpes zoster/shingles(Vostavax®: within last 10 years and must be prior to surgery), pneumonia (Pneumovax®),seasonal/H1N1 flu vaccines (as appropriate for season) for Groups B-E.

    In addition, for Group A:

    • Inability to ambulate for > 2 weeks secondary to lower extremity weakness and/or spasticity; the ALS Functional Rating Scale - Revised (ALSFRS-R) lower extremity subscore must be 1 or less. Patients who are non-ambulatory because of severe spasticity must have failed standard antispasticity treatment with baclofen (up to 120 mg/day) and/or tizanidine (up to 12 mg/day), physical therapy (PT), and occupational therapy (OT). Failure of antispasticity medications is defined as continued inability to walk unassisted even at the highest tolerated doses of these medications. Failure of PT and OT means continued inability to walk independently after maximum PT and OT intervention.
    • Vital capacity ≥ 60% of predicted normal for age, height and gender measured in the supine position at the time of screening and ≥ 50% of predicted normal for age,height and gender measured supine during the 7 days prior to surgery OR stable for at least 3 months with tracheostomy and invasive ventilation.
  12. In addition, for groups B and C:

    • Ambulatory subjects with impaired gait and approximately symmetrical lower extremity weakness and/or spasticity due to ALS and an ALSFRS-R gate subscore > 2.
    • Vital capacity ≥ 60% of predicted for age, height and gender measured in the supine position at the time of screening and ≥ 50% of predicted for age, height and gender measured supine during the 7 days prior to surgery
  13. In addition, for groups D and E:

    • Ambulatory subjects with impaired gait and symmetrical lower extremity weakness and/or spasticity due to ALS and an ALSFRS-R gate subscore > 2.
    • Upper extremity weakness affecting function with an ALSFRS-R arm subscale between 1 and 3.
    • Vital capacity ≥ 60% of predicted normal for age, height and gender measured in the supine position at the time of screening and ≥ 50% of predicted normal for age, height and gender measured supine during the 7 days prior to surgery.

Exclusion Criteria:

  1. Etiology of paraplegia or weakness is due to causes other than ALS such as spinal ischemia, traumatic spinal injury, traumatic brain injury, multiple sclerosis, cerebral stroke, cerebral palsy, or infection.
  2. VC < 60% predicted normal by standard nomogram at the time of screening and VC < 50% predicted normal measured supine for age at the time of surgery.
  3. Current or peak Panel Reactive Antibody (PRA) due to alloantibodies > 20% receiving their first allograft.
  4. Any known immunodeficiency syndrome.
  5. Receipt of any investigational drug,device or biologic within 30 days of surgery.
  6. Any concomitant medical disease or condition limiting the safety to participate:

    • Coagulopathy
    • Active uncontrolled infection
    • Hypotension requiring vasopressor therapy
    • Previous spinal surgery at the site of planned transplantation except for anterior cervical dissection fusion (ACDF)
    • Skin breakdown over the site of surgery
    • Malignancy (except for non-melanoma skin cancer)
    • Primary or secondary immune deficiency
    • Spinal stenosis.
  7. Creatinine >1.5, liver function tests (SGOT/SGPT, Bilirubin, Alk Phos) > 2x the upper limit of normal, hematocrit/hemoglobin < 30/10, total WBC < 4000, uncontrolled hypertension (defined as systolic >180 or diastolic >100) or uncontrolled diabetes(defined as hemoglobin A1C >8), evidence of GI bleeding by hemoccult test, positive tuberculosis (TB test: PPD/Mantoux), hepatitis B or C, or human immunodeficiency virus (HIV).
  8. Presence of any of the following conditions:

    • Current drug abuse or alcoholism
    • Unstable medical conditions
    • Unstable psychiatric illness including psychosis and untreated major depression within 90 days of screening
    • Positive blood test for hepatitis B or C.
  9. Any condition that the site PI feels may interfere with participation in the study.
  10. Any condition that the surgeon feels may pose complications for the surgery.
  11. Known hypersensitivity to basiliximab, tacrolimus, mycophenolate mofetil, or methylprednisolone.
  12. Inability to provide informed consent as determined by screening protocol.
  13. 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: NCT01348451

Locations
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Neuralstem Inc.
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Neuralstem Inc.
ClinicalTrials.gov Identifier: NCT01348451     History of Changes
Other Study ID Numbers: NS2008-1
Study First Received: April 28, 2011
Last Updated: January 3, 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