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

NCT01730716 | Unknown Phase 2 DMC

• 1 other identifier: NS2012-3
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

Brief Summary

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).

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Human spinal cord derived neural stem cell transplantation; ALS

Outcome Measures

Primary Outcomes (1)

• 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.

  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).

  Patients will be followed postoperatively for 24 months.

Secondary Outcomes (1)

• To evaluate neurologic deficits post spinal stem cell transplantation therapy.

  Patients will be followed postoperatively for 24 months.

Study Arms (1)

Surgery

EXPERIMENTAL

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

Interventions

Human spinal cord stem cell 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, 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.
• 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 and/or cervical laminectomy or laminoplasty as determined by the site Principal Investigator and neurosurgeon.
• Medically able to tolerate the immunosuppression regimen consisting of basiliximab, tacrolimus, mycophenolate mofetil, prednisone and methylprednisolone as determined by the site PI.
• Agrees to the visit schedule as outlined in the informed consent.
• Not taking riluzole (Rilutek®) or on a stable dose for ≥ 30 days.
• 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.
• 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.

You may not qualify if:

• Etiology of paraplegia or weakness is due to causes other than ALS.
• 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.
• 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 that the neurosurgeon deems to be an obstacle to the planned transplantation
• Skin breakdown over the site of surgery
• Malignancy (except for non-melanoma skin cancer)
• Spinal stenosis severe enough to preclude surgery (as determined by the neurosurgeon)
• Pre-existing kyphosis by preoperative MRI or X-ray
• Less than 5/5 grade in neck extension and strength test at the time of surgery.
• 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).

Sponsors & Collaborators

• Neuralstem Inc.: lead

Study Sites (3)

Emory University

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (2)

• 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 BACKGROUND

• 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 BACKGROUND

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 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2012
• First Posted: November 21, 2012
• Study Start: May 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: November 1, 2016
• Last Updated: April 20, 2015

Record last verified: 2013-05

Locations

US (3)