Study of Two Intrathecal Doses of Autologous Mesenchymal Stem Cells for Amyotrophic Lateral Sclerosis

Phase 1

• Conditions: AMYOTROPHIC LATERAL SCLEROSIS
• Interventions: Other: Two intrathecal MSC injections

• Registration Number: NCT02917681
• Lead Sponsor: University of Sao Paulo General Hospital

Brief Summary

The study aims to evaluate primarily safety of two injections of autologous mesenchymal stem cells in Amyotrophic Lateral Sclerosis patients. Secondary outcomes of efficacy will also be evaluated

Detailed Description

The study is an open-label, unmasked, uncontrolled phase I and II trial to evaluate safety and efficacy of two injections of autologous mesenchymal stem cells (MSC) in Amyotrophic Lateral Sclerosis (ALS) patients. Patients will be recruited trough a web-based registration system, open for all ALS Brazilian patients. The patients will be enrolled after in-person screening at the University of Sao Paulo Medical School Clinics Hospital and inclusion criteria fulfilled. There will be 9 national calls for registration, two months apart each. The enrolled patients will be followed for 3 months before bone marrow aspiration (BMA). Patients will receive 2 intrathecal MSC injections, 1 and 2 months after BMA. The patients will be followed for 6 months after the interventions.

Study Timeline

• Status Verified: 2016-09
• Study Start: 2016-09
• Study First Submitted: 2016-09-26
• Study First Submitted QC: 2016-09-27
• Last Update Submitted: 2016-09-27
• Study First Posted: 2016-09-28
• Last Update Posted: 2016-09-28
• Primary Completion: 2019-02
• Study Completion: 2019-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

1. Age between 18 and 70
2. Possible, probable or definite ALS following El Escorial Revised Criteria (Brooks, 2000)
3. ALSFRS-r ≥30 at enrollment
4. Forced Vital Capacity ≥65% of the height and weight standard
5. No-pregnancy agreement
6. Regional accessibility to the study site
7. Capability to give away agreed consensus
8. Patients will be followed at Academic Institutions at their hometown

Exclusion Criteria

1. Previous cellular therapy
2. Incapacity to lay still during bone marrow aspirate or intrathecal MSC injections
3. Personal history of auto-Immune, myeloproliferative or myelodysplastic diseases, leukemia, lymphoma, whole-body irradiation, hip fracture, severe scoliosis or incapacity to undergo any of the study's proposed procedures
4. Any other disease that may interfere with the study
5. Any other neurological diseases
6. Aspartate or alanine aminotransferases elevated >3x normality upper limit
7. Serum creatinine >2x normality upper limit
8. Hepatitis B and C, HIV, HTLV I and II and syphilis
9. Immunosuppressant drug use within 6 weeks from the study's screening
10. Pregnancy or breast-feeding
11. Acquired or inherited Immunodeficiency
12. Participation in other clinical trials
13. Non-invasive ventilation, tracheostomy or diaphragm pacing
14. Substance abuse within one year and other unstable mental health diseases according to researcher's judgement
15. Gastrostomy or any alternative feeding means
16. Inappropriate in-vitro MSC expansion

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MSC injection	Two intrathecal MSC injections	Patients will be followed for 3 months before bone marrow aspiration (BMA). Patients will receive 2 intrathecal MSC injections, 1 and 2 months after BMA. The patients will be followed for 6 months after the interventions.

Primary Outcome Measures

Name	Time	Method
Safety	10 months	Clinical and laboratory monitoring of possible reactions to intrathecal MSC delivery

Secondary Outcome Measures

Name	Time	Method
Change in Forced Vital Capacity (FVC)	10 months
Changes in morphometric parameters of MRI of encephalon and spinal cord	10 months
Change in Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R)	10 months	Specific scale for assessing ALS disease progression
Change in Isometric Strength	10 months
Change in Handheld dynamometry	10 months
Change in Electrical Impedance Myography	10 months

Trial Locations

Locations (1)

University of Sao Paulo School of Medicine Clinics Hospital; 🇧🇷 Sao Paulo, SP, Brazil