A Phase I, 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

Study Purpose:

The purpose of the study is to determine the feasibility, safety, and toxicity of human spinal cord-derived neural stem cell transplantation for the treatment of amyotrophic lateral sclerosis.

Disease:

Amyotrophic Lateral Sclerosis (ALS),  Familial ALS,  Sporadic ALS

Study Type:

Interventional Trial

Study Category:

Stem Cell , Device

Study Status:

Not enrolling

Phase:

Phase I

Study Chair(s)/Principal Investigator(s):

Eva Feldman, MD, PhD (University of Michigan)

Clinicaltrials.gov ID (11 digit #):

NCT01348451

Neals Affiliated?

Yes

Coordinating Center Contact Information

Massachusetts General Hospital
Elene McLoughlin / .(JavaScript must be enabled to view this email address) / 617-643-5374
.(JavaScript must be enabled to view this email address) 149 13th Street
Charlestown, Massachusetts 02129 United States

Full Study Summary:

Previous research has shown that on autopsy, ALS patients are found to have increased levels of the amino acid glutamate accumulated in the brain and spinal cord. This increase is thought to be caused by a decrease in the glutamate transporter which normally "cleans up" glutamate from the cells. Human spinal cord-derived neural stem cells (HSSC) are known to express amino acid transporters and it is hoped that this action will reduce the toxicity of accumulated glutamate and benefit ALS patients. A second hypothesized benefit of HSSC is their ability to secrete neurotrophic support factors. Neurotrophic factors support the health of nerves.

These stem cells have been engineered from the spinal cord of a single fetus electively aborted after eight weeks of gestation. The tissue was obtained with the mother's consent. The cells are transplanted into the ALS subject's spinal cord after laminectomy, an operation that removes bone surrounding the spine. After the spinal cord is exposed, a device manufactured for this purpose will be mounted onto the subject and will hold a syringe filled with the cells. The syringe will have a needle attached and the needle will enter the spinal cord at 5-10 locations injecting the cells. The device will minimize trauma to the spinal cord caused by the needle by making the punctures precise and steady, and by injecting the material at a slow and steady speed.

This study includes five groups of ALS subjects. The first three groups, A, B and C, have completed enrollment. The first group (A) included six subjects and the remaining groups have three subjects each. The groups have slightly different inclusion criteria and receive different procedures. The first group (A) included patients with advanced disease who were unable to walk. This group (A) included both ALS patients with the ability to breathe on their own as well as those with tracheostomies and ventilators. The first three subjects in group A underwent a laminectomy and received transplant injections of HSSC on one side of their lower spinal cord. The second three subjects in the first group (A) received transplant injections of HSSC on both sides of their lower spinal cord. Group B included ALS patients who were still ambulatory. They received transplant injections of HSSC on one side of their lower spine. Group C included ALS patients who were still ambulatory and received transplant injections on both sides of their lower spine. Group D patients will be ambulatory with some arm dysfunction and will receive transplant injections on one side of their neck. Lastly group E will include ALS patients who are ambulatory and will receive both injections on one side of their neck and injections on both sides of their lower spine. Because the HSSC are human in origin, subjects will receive immunosuppressive medications to prevent the rejection of the cells. Right before and immediately after surgery subjects will receive infusions of a drug called basiliximab. After surgery they will take prednisone and be tapered off that medication over one month. They will also be given two other immunosuppressive agents, tacrolimus and mycophenolate mofetil after surgery and it is expected that the subjects will take these drugs for the duration of their lives.

Study Sponsor:

Neuralstem Inc.

Participant Duration:

4 years + 3 months active study participation; lifetime follow-up

Estimated Enrollment:

18

Estimated Study Start Date:

12/31/2009

Estimated Study Completion Date:

11/02/2016

Posting Last Modified Date:

05/31/2012

Date Study Added to alsconsortium.org:

10/12/2011
  • More Information

    Enrolling BY INVITATION. Please click on "Site Contact Information" below for Emory contact information to learn more about enrollment in this trial.

  • Eligibility Criteria

    Gender:

    Female, Male

    Minimum Age:

    18

    Maximum Age:

    N/A

    Min Vital Capacity (% predicted normal):

    50

    Time since Symptom Onset:

    N/A

    Time since Diagnosis:

    N/A

    Can participants use Riluzole?

    Yes


    If taking riluzole, dose must be stable for three months; geographic accessibility to the site is required (Atlanta, GA); subjects must have a willing and able caregiver; have no unstable medical conditions and be medically able to tolerate the surgery and immunosuppressive medications.

  • Site Contact Information

    Emory University
    Jane Bordeau / .(JavaScript must be enabled to view this email address) / 404-727-1679
    Atlanta, Georgia 30322
    United States

  • Study Results