Neural Stem Cell Treatment for Amyotrophic Lateral Sclerosis (STEMALS)
ConditionAmyotrophic Lateral Sclerosis
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-65
SponsorCasa Sollievo della Sofferenza IRCCS
About this trial
A Not for Profit Phase II Study to Evaluate Safety, Efficacy and Biomarkers secondary endpoints of Human Neural Stem cell intracerebroventricular transplantation in amyotrophic lateral sclerosis patients: a randomized, placebo controlled, triple blind study.
This is an approximate 24-months study (PHASE B) consisting, per patient, of a 30-day screening period, 12-month enrollment and follow up period. A preliminary 3+3 dose-escalation open-label phase (PHASE A) will be performed in order to test the toxicity of the two proposed cell doses. The study will be stopped when all the subjects included in the treatment period complete the study visits. The study uses an ATMP, for that reason all the patients follow up will be prosecuted long life.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patient provides written informed consent, informed consent signature collection prior to any study procedure (patient has good acceptance and understanding of the informed consent);
Definite, probable diagnosis according to the revised El Escorial criteria;
Age: 18-65 years;
FVC >70%;
Disqualifiers
Psychiatric disease or other neurological diseases different from ALS;
Evidence of any concurrent illness or treatments limiting the safety to participate or any condition that the neurosurgeon feels may pose complications for the surgery;
Cancer within the previous 10 years;
Immunosuppressive therapy within 12 weeks of screening; active autoimmune disease or infection (including hepatitis B, hepatitis C, or HIV);
Trial design
Design model
Parallel
Treatments tested in this trial
human Neural Stem Cells (hNSC)
Procedure/SurgeryThe patient is placed on a regular operating room table with or without rigid head fixation. Procedure will be performed whether under general anesthesia or sedation and local anesthesia. Image guidance will be registered using the frameless stereotactic AxiEM system. Image guidance will be used to perform ventricular cannulation with the catheter passed over an electromagnetic-tipped stylet, which is recognized and tracked by the navigation system. The correct placement of the catheter is verified by the egress of CSF. Finally the electromagnetic stylet will be removed and a Rickam reservoir connect to ventricular catheter. Operative time will be about 30 minute. A post-operative CT scan will be obtained in all patients to confirm the catheter position.
Saline (Placebo)
Procedure/SurgeryThe patient is placed on a regular operating room table with or without rigid head fixation. Procedure will be performed whether under general anesthesia or sedation and local anesthesia. Image guidance will be registered using the frameless stereotactic AxiEM system. Image guidance will be used to perform ventricular cannulation with the catheter passed over an electromagnetic-tipped stylet, which is recognized and tracked by the navigation system. The correct placement of the catheter is verified by the egress of CSF. Finally the electromagnetic stylet will be removed and a Rickam reservoir connect to ventricular catheter. Operative time will be about 30 minute. A post-operative CT scan will be obtained in all patients to confirm the catheter position.
Treatment groups
30 Participants
are divided into 3 treatment groupsGroup A: hNSC 20*10^6Experimental treatment 1 intervention
Group B: hNSC 40*10^6Experimental treatment 1 intervention
Group C: Saline Solution (placebo)Placebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Safety of treatment
safety assessed with respect to the incidence of treatment-emergent AEs (TEAEs) and serious AEs (SAEs) over the whole study period
Time frame
From date of enrollment until 12 month.Secondary outcomes
1
Biological Endpoints
To evaluate the biological activity of hNSC treatment by measuring the levels of selected pharmacodynamics biomarkers in CSF and serum. Data will be statistically assessed for significance by either Student t test or analysis of variance as applicable. A p value of less than 0.05 will be considered statistically significant. Candidate markers include: lNf, GFAP, NF1, VEGF, Osteopontin, CXCL13, Cystatina, MCP-1 BDNF, YKL-40, IL-6, TNF-a, IL-17, TDP43 TAU In parallel to the clinical evaluation of hNSCs efficacy we will also develop patient-specific cell models in order to individuate molecular and cellular mechanisms supporting the putative therapeutic action of hNSCs treatment. These models will be derived from blood or skin cells of the patients recruited in the trial in order to produce iPS cells, then differentiated in NSCs. disease
Time frame
Samples for biological endpoints will be taken at treatment, 1, 3, and 6 months after treatmentSponsors and contacts
Click on the lead sponsor to view all of their trials.
Casa Sollievo della Sofferenza IRCCS
Lead sponsor
Ministry of Health, Italy
Collaborator
Source ClinicalTrials.gov