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.
These stem cells are called Human Spinal Stem Cells (HSSC) and have been engineered from the spinal cord of a single fetus electively aborted after 8 weeks of gestation. The tissue was obtained with the mother's consent. The cells will be transplanted into the ALS patient'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 patient and will hold a syringe filled with the cells. The syringe will have a needle attached and the needle will enter the spinal cord in specified areas. The device will minimize trauma to the spinal cord by the needle by making the puncture precise and steady and injecting the material at a slow and steady speed. ALS is a universally fatal neurodegenerative condition that causes weakness leading to paralysis and death. Life expectancy is 2-5 years. The cause is unknown and there is no effective treatment. 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. Because the HSSC are human in origin, their transplantation will be handled in some ways like other organ transplants in that patients will receive immunosuppressive medications to prevent the rejection of the cells. Right before and immediately after surgery patients 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 patients will take these drugs for the rest of their lives.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
human spinal cord stem cell implantation in ALS patients
Emory University
Atlanta, Georgia, United States
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.
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.
The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population.
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.
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.
The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population.
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.
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.
The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population.
3\. Hand grip (bilateral) will be measured using the Jaymar Grip dynamometer.
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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.
The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population.
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.
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.
The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population.
5\. Negative Inspiratory Force (NIF) will be measured with a Negative Inspiratory Force Gauge (Instrumentation Industries).
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.
The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population.
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 .
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.
The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population.
7\. Comprehensive pain assessment utilizing the Neuropathic Pain Scale (NPS).
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.
The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population.
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.
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.
The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population.
9\. Urodynamic parameters including incontinence and urinary retention measured by post void residual.
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.
The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population.
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
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.
The Secondary Objectives of the study are to evaluate spinal stem cell transplantation therapy in this patient population.
11\. Ashworth Spasticity Scale.
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.