NCT01051882

Brief Summary

The study will evaluate the safety, tolerability and therapeutic effects (preliminary efficacy) of injection of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF), as a possible treatment for patients with Amyotrophic Lateral Sclerosis (ALS) at the early and progressive disease stages.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jun 2011

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 17, 2010

Completed
3 days until next milestone

First Posted

Study publicly available on registry

January 20, 2010

Completed
1.4 years until next milestone

Study Start

First participant enrolled

June 1, 2011

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2012

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2013

Completed
Last Updated

January 10, 2019

Status Verified

August 1, 2012

Enrollment Period

1.5 years

First QC Date

January 17, 2010

Last Update Submit

January 8, 2019

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Mesenchymal Stromal Cells (MSC)Amyotrophic Lateral Sclerosis (ALS)NeuroprotectionNeurodegenerationStem cellsALS

Outcome Measures

Primary Outcomes (2)

  • Safety evaluation and tolerability of a single treatment administration of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF)

    Safety evaluation and tolerability of a single treatment administration of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF) by multiple intramuscular injections (IM) at 24 separate sites on the biceps and triceps muscles to patients with ALS at the early disease stage

    6 months

  • Safety evaluation and tolerability of single intrathecal injection (IT) into the cerebrospinal fluid (CSF) of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF)

    Safety evaluation and tolerability of single intrathecal injection (IT) into the cerebrospinal fluid (CSF) of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF),to patients with ALS at the progressive disease stage.

    6 months

Secondary Outcomes (8)

  • Changes in the progression rate of the disease as evidenced by changes in the ALS functional rating scale (ALS-FRS)

    6 months

  • Changes in muscle strength grading (MVIC) by muscle chart

    6 months

  • Changes in forced vital capacity (FVC %) (In the progressive disease stage group only).

    6 months

  • Changes in muscle bulk estimated by MRI of the upper and lower extremities

    6 months

  • Changes in upper and lower extremities circumference (cm)

    6 months

  • +3 more secondary outcomes

Study Arms (2)

MSC-NTF cells IM

EXPERIMENTAL

Intramuscular administration in early stage patients

Biological: MSC-NTF cells transplantation (IM)

MSC-NTF cells IT

EXPERIMENTAL

Intrathecal administration in progressive stage patients

Biological: MSC-NTF cells transplantation (IT)

Interventions

MSC-NTF cells transplantation (IM)BIOLOGICAL

In early ALS subjects: Autologous MSC-NTF cells will be transplanted under mild anesthesia, intramuscularly into patients' clinically unaffected (or only mildly affected) upper arm biceps and triceps muscles according to a pre-designed grid. Intramuscular injections will be by a 26 gauge needle to a 1.5cm depth (ensuring that injection is into muscle and not adipose tissue). The patients will be injected at 24 sites with a total of 24 million cells

MSC-NTF cells IM
MSC-NTF cells transplantation (IT)BIOLOGICAL

In progressive ALS subjects: Autologous MSC-NTF cells will be transplanted under mild anesthesia intrathecally(via a standard lumbar puncture)with a total of 60 million cells.

MSC-NTF cells IT

Eligibility Criteria

Age20 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • El Escorial criteria for definite or probable ALS
  • Either men or non pregnant women between 20-75 years of age.
  • Patient is mentally intact and psychologically stable
  • For early stage ALS- Patients will be with ALS-FRS-R scale of at least 30 and disease duration of less than 2 years.Or, for progressive stage ALS- Patients will be with an ALS-FRS-R scale of 15-30 and disease duration of less than 2 years
  • For early stage ALS- Patient has sufficiently bulky muscles. Or, for progressive stage ALS- Patient with at least 60% FVC
  • Participant understands the nature of the procedure and provides written informed consent prior to any study procedure.

You may not qualify if:

  • Positive test for HBV, HCV, HIV and Mycoplasma.
  • High protein in the CSF.
  • Lymphocytosis in the CSF.
  • Positive for anti-GM1 antibodies.
  • Patient has significant conduction blocks or slow nerve conduction velocities (a reduction of more than 30%) confirmed by nerve conduction velocity - EMG studies.
  • The patient is a respiratory dependent.
  • Renal failure, impaired hepatic function
  • Patients suffering from significant cardiac disease, malignant diseases or any other disease that may risk the patient or interfere with the ability to interpret the results
  • Active infections.
  • Participation in another clinical trial within 1 month prior to start of this study.
  • Subject unwilling or unable to comply with the requirements of the protocol.
  • Patient has not been treated previously with any cellular therapy.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hadassah Medical Organization

Jerusalem, 91120, Israel

Location

Related Publications (1)

  • Petrou P, Gothelf Y, Argov Z, Gotkine M, Levy YS, Kassis I, Vaknin-Dembinsky A, Ben-Hur T, Offen D, Abramsky O, Melamed E, Karussis D. Safety and Clinical Effects of Mesenchymal Stem Cells Secreting Neurotrophic Factor Transplantation in Patients With Amyotrophic Lateral Sclerosis: Results of Phase 1/2 and 2a Clinical Trials. JAMA Neurol. 2016 Mar;73(3):337-44. doi: 10.1001/jamaneurol.2015.4321.

    PMID: 26751635DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral SclerosisNerve Degeneration

Condition Hierarchy (Ancestors)

Spinal Cord DiseasesCentral Nervous System DiseasesNervous System DiseasesMotor Neuron DiseaseNeurodegenerative DiseasesTDP-43 ProteinopathiesNeuromuscular DiseasesProteostasis DeficienciesMetabolic DiseasesNutritional and Metabolic DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Dimitrios Karussis, MD, PhD

    Hadassah Medical Organization

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 17, 2010

First Posted

January 20, 2010

Study Start

June 1, 2011

Primary Completion

December 1, 2012

Study Completion

March 1, 2013

Last Updated

January 10, 2019

Record last verified: 2012-08

Locations

IL(1)