Overview

This trial is active, not recruiting.

Condition multiple sclerosis
Treatment injection of autologous stem cells
Phase phase 1/phase 2
Sponsor Hadassah Medical Organization
Start date October 2006
End date December 2009
Trial size 20 participants
Trial identifier NCT00781872, MS22MSC-HMO-CTIL

Summary

Multiple sclerosis is a multifocal inflammatory disease of the central nervous system which affects young individuals and causes paralysis of the limbs, sensation, visual and sphincter problems. The disease is caused by an autoimmune mechanism, ie the immune system produces antibodies and cells which attack the self myelin antigens, causing therefore demyelination. The disease is clinically evident with relapses of neurological disability due to the dysfunction of the areas (plaques of multiple sclerosis) in which damage of myelin occurs. Disability can accumulate with time and the disease enters a progressive phase due to damage of the axons and irreversible neurodegeneration. Although, effective immunotherapies exist which downregulate the autoimmune anti-myelin reactivity and reduce the rate of relapses of MS (like Copaxone and interferons), there is no effective means today to stop the progression of disability and induce rebuilding of the destroyed myelin (re-myelination). Neuronal stem cells were shown to possess the ability to restore neuronal activity and produce new neurons through transdifferentiation. Various other types of stem cells were tested in animal models with promising results, revealing a potential for restoration of the neurological function in neuroimmune and neurodegenerative conditions and in central nervous system traumatic injury. Adult bone marrow derived stromal cells (MSC) were shown to induce similar (to the neuronal stem cells) immunomodulatory and neuroregenerative effects and were shown in our laboratory to induce neuroprotection in the animal model of chronic experimental autoimmune encephalomyelitis (EAE). These bone marrow derived MSCs offer practical advantages for clinical therapeutic applications, since they can be obtained from the adult bone marrow and therefore the patient can be the donor for himself, without any danger for rejection of the cells. In addition, MSCs carry a safer profile and are less prone to malignant transformation.

Our initial clinical experience with 10 patients with ALS and 10 with multiple sclerosis show that intravenous and intrathecal administration of MSCs is feasible and safe.

In this study we propose an explorative protocol with the injection of MSCs (both intrathecally and intravenously) in patients with MS, in an effort to prevent further neurodegeneration through neuroprotective mechanisms and induce neuroregeneration and restoration of neuronal function. This will be a phase I/II study.

The primary endpoint will be to further evaluate the safety and feasibility of the treatment with MSC infusions, in MS patients. Additionally, the migration ability of the transplanted cells will be evaluated by tagging MSCs with the superparamagnetic iron oxide particle (Feridex) (an FDA approved cell tracking drug) for detection by MRI. MRI of the brain and spinal cord will be performed at weeks 1, 4, 12 and 24 to detect the migration of the stem cells. Clinically the patients will be followed by monthly evaluations of the MS functional rating scale (EDSS) scale. The MRI, will be also used to evaluate changes in the total volume of lesions in the brain and the degree of atrophy.

Significance: Our center has performed the first clinical trial with intrathecal and intravenous injection of adult stem cells in MS and ALS patients and has gained experience during the last 3 years with this type of stem cells treatment. After having evaluated the safety and feasibility issues, we intent to proceed to the second stage, to evaluate the migration ability of those cells (their ability to reach the affected motor areas of the CNS gray matter, by tracking them with a paramagnetic material and visualize them by MRI), and evaluate indications of clinical efficacy. This project may provide information for possible therapeutic uses of this type of bone marrow adult stem cells in MS and ALS but may also serve as a pilot platform and pave the path for future applications of various types of stem cells in neurodegerative diseases in general.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
a group of patients with active multiple sclerosis, failures to respond to other treatments
injection of autologous stem cells stromal cells of bone marrow
60 milion cells intrathecally and 20 milion intravenously

Primary Outcomes

Measure
safety and migration ability of the injected cells
time frame: one year

Secondary Outcomes

Measure
clinical efficacy in disability score
time frame: one year

Eligibility Criteria

Male or female participants from 35 years up to 65 years old.

Inclusion Criteria: 1. Consenting patients fulfilling the Poser's clinical criteria for definite MS 2. Age: 35-65, males and females 3. Duration of disease: >5 years 4. Failure to the currently available -registered- for MS immunomodulatory treatments (ie interferons, Copaxone, immunosuppression): the lack of response to (at least two) of these treatments will be determined/defined by either an increase (deterioration) of at least one degree in the EDSS score during the last year or the appearance of at least two major relapses of MS during the same period of time (under treatment). Exclusion criteria 1. Patients who were treated with cytotoxic medications (cyclophosphamide, Mitoxanthrobne etc) during the last 3 months prior to the inclusion 2. Patients suffering from significant cardiac, renal or hepatic failure or any other disease that may risk the patient or interfere with the ability to interpret the results 3. Patients with active infections 4. Patients with severe cognitive decline or inability to understand and sign the informed consent

Additional Information

Official title Explorative Trial to Investigate the Migration Ability of Mesenchymal Bone Marrow Stem Cells (MSC) in the Central Nervous System (CNS) Following Their Intrathecal Administration in Severe Cases of Multiple Sclerosis (MS)
Principal investigator Dimitrios Karussis, Prof.
Trial information was received from ClinicalTrials.gov and was last updated in October 2008.
Information provided to ClinicalTrials.gov by Hadassah Medical Organization.