Escalated Application of Mesenchymal Stem Cells in Amyotrophic Lateral Sclerosis Patients

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

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.

Study Overview

• Status: Completed
• Conditions: Motor Neuron Disease
• Intervention / Treatment: Biological: Autologous Mesenchymal stem cells (MSCs)

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Sao Paulo, SP, Brazil, 01236-030
      • Instituto de Ensino e Pesquisas - IEP-São Lucas
  • Sao Paulo
    • Santo Andre, Sao Paulo, Brazil, 09030010
      • Hospital e Maternidade Dr Christóvão da Gama

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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: Autologous Mesenchymal stem cells; Two escalated intrathecal infusions of autologous mesenchymal stem cell	Biological: Autologous Mesenchymal stem cells (MSCs); 2 intrathecal autologous MSCs infusions (1x10^8 cells) will be performed, escalated from 30 days apart

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hospital e Maternidade Dr. Christóvão da Gama
• Collaborators: IEP São Lucas - Instituto de Ensino e Pesquisa; Clinica Jordy Sinapse; TECHLIFE - Centro de Tecnologia Celular
• Investigators: Study Director: Leandro B Agati, PhD, Hospital e Maternidade Dr Christóvão da Gama; Study Chair: Eliseo J Sekiya, MD, PhD, Instituto de Ensino e Pesquisas - IEP-São Lucas; Study Chair: Adelson A Silva, MD, Instituto de Ensino e Pesquisas - IEP-São Lucas; Study Chair: Andresa Forte, MSc, TECHLIFE - Centro de Tecnologia Celular; Study Chair: Sergio S Jordy, MD, Clínica Jordy Sinapse

Publications and helpful links

Helpful Links

• Institutional website

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2015
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): April 5, 2017

Study Registration Dates

• First Submitted: July 1, 2016
• First Submitted That Met QC Criteria: December 8, 2016
• First Posted (Estimate): December 9, 2016

Study Record Updates

• Last Update Posted (Actual): August 7, 2017
• Last Update Submitted That Met QC Criteria: August 4, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis
• 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: HospitalMCG; IEPSaoLucas (Other Identifier: IEP Sao Lucas)