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

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

Study Overview

• Status: Unknown
• Conditions: AMYOTROPHIC LATERAL SCLEROSIS
• Intervention / Treatment: Other: Two intrathecal MSC injections

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 Type: Interventional
• Enrollment (Anticipated): 28
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Sao Paulo, SP, Brazil, 05403000
      • Recruiting
      • University of Sao Paulo School of Medicine Clinics Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: MSC injection; 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.	Other: Two intrathecal MSC injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	Clinical and laboratory monitoring of possible reactions to intrathecal MSC delivery	10 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Collaborators: Pontifícia Universidade Católica do Paraná
• Investigators: Principal Investigator: Gerson Chadi, MD, PhD, Full Professor

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Anticipated): February 1, 2019
• Study Completion (Anticipated): August 1, 2019

Study Registration Dates

• First Submitted: September 26, 2016
• First Submitted That Met QC Criteria: September 27, 2016
• First Posted (Estimate): September 28, 2016

Study Record Updates

• Last Update Posted (Estimate): September 28, 2016
• Last Update Submitted That Met QC Criteria: September 27, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: ALS; mesenchymal stem cells; intrathecal
• 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: 401922/2014-6

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO