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

• ClinicalTrials.gov Identifier: NCT01640067
• Recruitment Status: Completed
• First Posted: July 13, 2012
• Last Update Posted: December 30, 2015
• Sponsor: Azienda Ospedaliera Santa Maria, Terni, Italy
• Collaborators: Azienda Ospedaliero Universitaria Maggiore della Carita; Università di Padova Italy
• Information provided by (Responsible Party): Angelo Luigi Vescovi, Azienda Ospedaliera Santa Maria, Terni, Italy

Tracking Information

• First Submitted Date: July 9, 2012
• First Posted Date: July 13, 2012
• Last Update Posted Date: December 30, 2015
• Study Start Date: December 2011
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 11, 2012)

safety of a microsurgery human neural stem cells transplantation into spinal cord of ALS patients [ Time Frame: Participants will be followed for at least 3 years. Monthly in the first year and every three months the following two years ]

• 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

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Human Neural Stem Cell Transplantation in Amyotrophic Lateral Sclerosis (ALS)
• Official Title: 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

Brief Summary

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)

• 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
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label)
• Condition: Amyotrophic Lateral Sclerosis

Intervention

Biological: Human Neural Stem Cells

Surgical microinjection of human neural stem cells on spinal cord of ALS patients

Other Name: Human Neural Stem Cells Suspension

Study Arms

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.

Intervention: Biological: Human Neural Stem Cells

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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 11, 2012): 18
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 2015
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT01640067
• Other Study ID Numbers: EudraCT: 2009-014484-39
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Angelo Luigi Vescovi, Azienda Ospedaliera Santa Maria, Terni, Italy
• Original Responsible Party: Same as current
• Current Study Sponsor: Azienda Ospedaliera Santa Maria, Terni, Italy
• Original Study Sponsor: Same as current

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

• PRS Account: Azienda Ospedaliera Santa Maria, Terni, Italy
• Verification Date: December 2015