Escalated Application of Mesenchymal Stem Cells in Amyotrophic Lateral Sclerosis Patients

Study Overview
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Brief Summary
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Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that selectively affects motor neurons in the brain and spinal cord, leading to bulbar, respiratory, and limb weakness. There is no effective treatment, and the disease usually progresses to death within 2 to 4 years. The therapeutic plasticity of mesenchymal stem cells (MSCs) may be an attractive therapy to this complex disease, turning MSCs strong candidates for cellular therapy in ALS. Design-A phase 1 open-safety clinical trial. 4 patients will be selected according to a restricted inclusion and exclusion criteria and after 2 escalated infusions of MSCs, there will be a follow up period of one year Methods - Primary endpoint: safety of mesenchymal autologous stem cells infusions escalated in two intrathecal administrations in patients with ALS defined as severe adverse events (SAe). Secondary endpoints: clinical response, laboratorial and magnetic resonance imaging of patients submitted to cellular escalating doses applied in the study. Quality of life, according to El Escorial criteria, ALSFR scale and functional scales. Conclusion: This study is a primary step before a large randomized double-blind clinical trial for ALS. It is expected to confirm the safety of escalated MSCs therapy in ALS patients, initial data of efficacy in addition to improved quality of life.

Official Title
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Safety and Efficacy of Mesenchymal Stem Cells Escalated Application in Amyotrophic Lateral Sclerosis Patients: Study Design of a Phase I Trial

Conditions
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Motor Neuron Disease

Intervention / Treatment
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* Biological: Autologous Mesenchymal stem cells (MSCs)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women and males over 18-year-old. Diagnosis of ALS in agreement with the criteria of EL SCORE Less than 24 months of evolution of the disease (from the beginning of the symptoms). Good understanding of the protocol and aptitude to grant the informed consent Infertile women (post-menopause or hysterectomized) Brazilian citizen and permanent resident. Exclusion Criteria: Any significant medical condition (congestive heart failure, angina, respiratory failure, and others) Any auto-immune disease Any malignant diseases Systemic infection Mental illness Depressive state

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous Mesenchymal stem cells<br>Two escalated intrathecal infusions of autologous mesenchymal stem cell | Biological: Autologous Mesenchymal stem cells (MSCs)<br>* 2 intrathecal autologous MSCs infusions (1x10^8 cells) will be performed, escalated from 30 days apart<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serious Adverse Events related to the treatment | Serious Adverse Events (Death, Life-threatening, Disability or Permanent Damage) will be monitored and documented during follow up | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Revised ALS Functional Rating Scale (ALSFRS-R) | Quality of life from patients according to functional scales will be evaluated before and after interventions with 1, 3, 6 and 12 months. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amyotrophic Lateral Sclerosis