Human Neural Stem Cell Transplantation in Amyotrophic Lateral Sclerosis (ALS) (hNSCALS)

Intra-spinal Cord Delivery of Human Neural Stem Cells in ALS Patients: Proposal for a Phase I Study/ Trapianto Intramidollare di Cellule Staminali Neurali Umane Come Terapia Putativa Per la SLA: Proposta di un Trial Clinico di Fase I

Primary aim of the trial

1. to verify safety and tolerability of expanded human fetal neural stem cells
2. to verify safety and tolerability of a microsurgery human fetal neural stem cells transplantation model
3. to recognize each change in patient's quality of life

Secondary aim of the trial

1. assessment of the impact of human neural stem cells transplantation on the disability of ALS in a clinically significant and measurable way
2. Assessment of the impact of human neural stem cells transplantation on mortality (all causes)

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Biological: Human Neural Stem Cells

Detailed Description

18 patients diagnosed as definite ALS according to the El Escorial criteria will be recruited during two years. The patients will be divided into 3 groups with different severity. Each group will be less compromised than the group that went before them. Their breathing measurements must be at least 60%. Subjects will receive injections of the human foetal neural stem cells into the spinal cord. A variety of tests and examinations will take place every month for the first year and every three months for the next two in order to monitor the course of the disease and the adverse events.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Italy
  • Terni, Italy, 05100
    • Azienda Ospedaliera Santa Maria

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of definite or possible ALS according to revised EL Escorial criteria
• Age: 20-75 years
• documented progression of disease during the last 6 months.
• Absence of concomitant diseases
• Adequate assurances of adherence to protocol
• The patient must be able to communicate verbally or with the use of non-verbal communication system

Group 1

• maximum score of 1 on walking item of ALS functional rating scale
• forced vital capacity > or equal to 60

Group 2

• forced vital capacity > or equal to 60
• ambulation difficulties (maximum score of 2 on walking item of ALS functional rating scale)

Group 3

• Independent ambulation (score 4 on a scale ALS-FRS)
• forced vital capacity > or equal to 70

Exclusion Criteria:

The presence of at least one of the following will lead to patient exclusion.

1. psychiatric diseases or other neurological diseases different from ALS
2. other systemic diseases
3. Neoplasms or other diseases reducing life expectancy
4. Antecedent polio infection
5. corticosteroids, immunoglobulin or immunosuppressive treatment
6. involvement in other clinical trials
7. 2 or more critical items in MMPI
8. neuropsychological evaluation suggestive of mental deterioration or cognitive sphere disturbance.
9. Impediments to MRI
10. patients unable to understand informed consent form and study aims.
11. women who are pregnant or childbearing potential for the duration of the study. Non-pregnant status will be documented by beta-HCG negative test 7 days before treatment start

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Human Neural Stem Cells Suspension; 50,000 cells/µl. Patients received either unilateral or bilateral hNSCs microinjections (3 microinjections on each side) into the lumbar spinal cord. Each microinjection consisted of 15 µl of the above 50,000cells/µl suspension, yielding a total of 750,000 cells per injection site.	Biological: Human Neural Stem Cells; Surgical microinjection of human neural stem cells on spinal cord of ALS patients; Other Names: Human Neural Stem Cells Suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety of a microsurgery human neural stem cells transplantation into spinal cord of ALS patients	Percentage of subjects (%) with treatment-related mortality defined as death due to procedure and not to the course of the disease; Number of adverse events related to the procedure; Changes in neuroradiological (MRI) and neurophysiological variables (SEP, MEP); Changes in neuropsychological variables	Participants will be followed for at least 3 years. Monthly in the first year and every three months the following two years

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera Santa Maria, Terni, Italy
• Collaborators: Azienda Ospedaliero Universitaria Maggiore della Carita; Università di Padova Italy
• Investigators: Principal Investigator: Angelo L Vescovi, Professor, IRCCS Casa Sollievo della Soffernza and AOSP Terni, Italy

Publications and helpful links

General Publications

• Gelati M, Profico D, Projetti-Pensi M, Muzi G, Sgaravizzi G, Vescovi AL. Culturing and expansion of "clinical grade" precursors cells from the fetal human central nervous system. Methods Mol Biol. 2013;1059:65-77. doi: 10.1007/978-1-62703-574-3_6.
• Gelati M, Profico DC, Ferrari D, Vescovi AL. Culturing and Expansion of "Clinical Grade" Neural Stem Cells from the Fetal Human Central Nervous System. Methods Mol Biol. 2022;2389:57-66. doi: 10.1007/978-1-0716-1783-0_5.
• Mazzini L, Gelati M, Profico DC, Sgaravizzi G, Projetti Pensi M, Muzi G, Ricciolini C, Rota Nodari L, Carletti S, Giorgi C, Spera C, Domenico F, Bersano E, Petruzzelli F, Cisari C, Maglione A, Sarnelli MF, Stecco A, Querin G, Masiero S, Cantello R, Ferrari D, Zalfa C, Binda E, Visioli A, Trombetta D, Novelli A, Torres B, Bernardini L, Carriero A, Prandi P, Servo S, Cerino A, Cima V, Gaiani A, Nasuelli N, Massara M, Glass J, Soraru G, Boulis NM, Vescovi AL. Human neural stem cell transplantation in ALS: initial results from a phase I trial. J Transl Med. 2015 Jan 27;13:17. doi: 10.1186/s12967-014-0371-2.
• 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.

Helpful Links

• No profit Association that grant this study

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: July 9, 2012
• First Submitted That Met QC Criteria: July 11, 2012
• First Posted (Estimate): July 13, 2012

Study Record Updates

• Last Update Posted (Estimate): December 30, 2015
• Last Update Submitted That Met QC Criteria: December 29, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: safety; stem cells; amyotrophic lateral sclerosis; motor neuron disease; Survival analysis; ALS-FRS-Functional scale R and FVC (%) variation; Changes in quality of life scales
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: EudraCT: 2009-014484-39