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

NCT01348451 | Unknown Phase 1 DMC

• 1 other identifier: NS2008-1
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Human spinal cord derived neural stem cell transplantation; ALS

Outcome Measures

Primary Outcomes (1)

• 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.

  The primary outcome measure is the incidence of adverse events in the study population.

  The primary outcome measure will be assessed at study visits pre and post surgery follow-up visits, for a total of 48 months.

Secondary Outcomes (11)

• The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population.

  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.

• The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population.

  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.

• The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population.

  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.

• The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population.

  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.

• The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population.

  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.

Study Arms (1)

surgery

EXPERIMENTAL

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

Interventions

surgical implantation DEVICE

human spinal cord stem cell implantation in ALS patients

surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• Age 18 years or older.
• 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 \[hysterectomy, oophorectomy or surgical sterilization\]).
• Geographic accessibility to the study center and the ability to travel to the clinic for study visits.
• Presence of a willing and able caregiver.
• Medically able to undergo lumbar or cervical laminectomy as determined by the Investigator, surgeon and anesthesiologist.
• Medically able to tolerate immunosuppression regimen consisting of basiliximab, tacrolimus, mycophenolate mofetil, and methylprednisolone as determined by the site Investigator.
• Agrees to the visit schedule as outlined in the informed consent.
• Not taking riluzole (Rilutek®) or on a stable dose for ≥30 days.
• 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.

You may not qualify if:

• 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.
• 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.
• Current or peak Panel Reactive Antibody (PRA) due to alloantibodies \> 20% receiving their first allograft.
• Any known immunodeficiency syndrome.
• Receipt of any investigational drug,device or biologic within 30 days of surgery.
• 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.
• 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).

Sponsors & Collaborators

• Neuralstem Inc.: lead

Study Sites (1)

Emory University

Atlanta, Georgia, 30322, United States

Location

Related Publications (7)

• Boulis NM, Federici T, Glass JD, Lunn JS, Sakowski SA, Feldman EL. Translational stem cell therapy for amyotrophic lateral sclerosis. Nat Rev Neurol. 2011 Dec 13;8(3):172-6. doi: 10.1038/nrneurol.2011.191.

  PMID: 22158518 BACKGROUND

• Lunn JS, Sakowski SA, Federici T, Glass JD, Boulis NM, Feldman EL. Stem cell technology for the study and treatment of motor neuron diseases. Regen Med. 2011 Mar;6(2):201-13. doi: 10.2217/rme.11.6.

  PMID: 21391854 BACKGROUND

• Glass JD. The promise and the reality of stem-cell therapies for neurodegenerative diseases. Cerebrum. 2010 Nov;2010:24. Epub 2010 Dec 15.

  PMID: 23447769 BACKGROUND

• Boulis N, Federici T. Surgical approach and safety of spinal cord stem cell transplantation. Neurosurgery. 2011 Feb;68(2):E599-600. doi: 10.1227/NEU.0b013e3182095e2e. No abstract available.

  PMID: 21654562 BACKGROUND

• Glass JD, Boulis NM, Johe K, Rutkove SB, Federici T, Polak M, Kelly C, Feldman EL. Lumbar intraspinal injection of neural stem cells in patients with amyotrophic lateral sclerosis: results of a phase I trial in 12 patients. Stem Cells. 2012 Jun;30(6):1144-51. doi: 10.1002/stem.1079.

  PMID: 22415942 RESULT

• Riley J, Federici T, Polak M, Kelly C, Glass J, Raore B, Taub J, Kesner V, Feldman EL, Boulis NM. Intraspinal stem cell transplantation in amyotrophic lateral sclerosis: a phase I safety trial, technical note, and lumbar safety outcomes. Neurosurgery. 2012 Aug;71(2):405-16; discussion 416. doi: 10.1227/NEU.0b013e31825ca05f.

  PMID: 22565043 RESULT

• Robberecht W, Philips T. The changing scene of amyotrophic lateral sclerosis. Nat Rev Neurosci. 2013 Apr;14(4):248-64. doi: 10.1038/nrn3430. Epub 2013 Mar 6.

  PMID: 23463272 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2011
• First Posted: May 5, 2011
• Study Start: January 1, 2009
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2016
• Last Updated: March 10, 2016

Record last verified: 2016-03

Locations

US (1)