Clinical trial NCT01640067: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Amyotrophic Lateral Sclerosis
Keywords: amyotrophic lateral sclerosis
motor neuron disease
stem cells
safety
ALS-FRS-Functional scale R and FVC (%) variation
Survival analysis
Changes in quality of life scales
Lead sponsor: Azienda Ospedaliera Santa Maria, Terni, Italy
Sponsor class: OTHER
Collaborators: name: Azienda Ospedaliero Universitaria Maggiore della Carita
name: Università di Padova Italy
First posted: 2012-07-13
Enrollment: 18
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

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.

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

Primary outcomes:
measure: safety of a microsurgery human neural stem cells transplantation into spinal cord of ALS patients
timeFrame: Participants will be followed for at least 3 years. Monthly in the first year and every three months the following two years
Secondary outcomes:
Other outcomes:
Locations:
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria
Study officials:
affiliation: IRCCS Casa Sollievo della Soffernza and AOSP Terni, Italy
name: Angelo L Vescovi, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.