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Intrathecal Autologous ADRC Treatment of Autoimmune Refractory Epilepsy (EPIMSC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03676569
Recruitment Status : Active, not recruiting
First Posted : September 18, 2018
Last Update Posted : April 9, 2019
Sponsor:
Collaborator:
Institution of Mother and Child, Warsaw, Poland
Information provided by (Responsible Party):
Anna Sarnowska, Mossakowski Medical Research Centre Polish Academy of Sciences

Brief Summary:

Refractory epilepsies caused by an autoimmune mechanisms lead in children to progressive neurodegeneration. Immunomodulation therapy is effective only in a half of such cases. New approaches are undertaken. It was found that ADRC (adipose derived regenerative cells) isolated from adipose tissue consist mesenchymal stem cells that act as tissue repair cells. The purpose of this experimental study is to evaluate the possibility and safety of the use of multipotent mesenchymal adipose derived regenerative cells (ADRC) in patients diagnosed with an autoimmune determined refractory epilepsy.

Study protocol:

Intrathecal infusions of autologous ADRC obtained after liposuction followed by isolation by Cytori system will be performed. Procedure will be repeated 3 times every 3 months in each patient. Neurological status, brain MRI, cognitive function and antiepileptic effect will be supervised during 24 months.


Condition or disease Intervention/treatment Phase
Refractory Epilepsy Biological: ADRC transplantation in autoimmune refractory epilepsy Phase 1

Detailed Description:

Epilepsy is a chronic neurological disorder diagnosed in about 1% of the population, or c. 400,000 patients in Poland. Autoimmune refractory epilepsy is rare but most disabled epilepsy leading to developmental regression. The belief in a positive effect of ADRCs in drug-resistant epilepsy comes from test results showing the ability of mesenchymal cells to concentrate in damaged tissues, as well as their strong immunomodulating, especially anti-inflammatory, properties. Patients with drug resistant epilepsy show decreased numbers of neurons within the epilepsy zone, with most of these being hyperactive and malfunctioning. Additionally, an inflammatory active reaction in affected brain tissue is visible. ADRC-induced activation of endogenous neurogenesis may increase chances that the epilepsy zone will be reduced, and give a positive impact as regards the neuropsychiatric disorders commonly present in patients with epilepsy. Another common process accompanying recurring epilepsy attacks is active inflammation. Per the literature, ADRCs show strong neuroprotective, immunomodulating and antiapoptotic qualities and they may potentially reduce the frequency of epilepsy attacks. Thus, a clinical trial with ADRCs, addressed to drug-resistant epilepsy sufferers would be promising in controlling the epileptic seizures and coexisting behavioral / psychiatric symptoms. The goal is to improve the quality of life of the patients and their caregivers.

In patients who were diagnosed with autoimmune drug-resistant epilepsy and have met the set criteria and qualified to take part in the examination, after a formal written consent of their parents at the Clinic of Child Neurology IMC neurological examination, routine laboratory tests, EEG and neuropsychological assessment will be performed. ADRC will be obtained after liposuction and isolation with Cytori system.

Before intrathecal transplantation of ADRC suspension ( 5 ml), cerebrospinal fluid will be collected for evaluation of origin protein level, oligoclonal bands, the IgG index as well as GluR3, VGKC complex/LGI1, GM1, NT-3, GAD, and NMDAR antibodies. At the same time there will be an intake of 5ml of serum to evaluate levels of immunoglobulins IgA, IgM and IgG.

Procedure will be repeated 3 times every 3 months in each patient. Neurological status, brain MRI, cognitive function and antiepileptic effect will be supervised during 24 months.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Experimental clinical treatment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Intrathecal Autologous Adipose Derived Regenerative Cells Treatment of Autoimmune Determined Refractory Epilepsy - Evaluation of Safety and Efficacy
Actual Study Start Date : November 15, 2015
Estimated Primary Completion Date : November 10, 2019
Estimated Study Completion Date : November 10, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Epilepsy

Arm Intervention/treatment
Experimental: Experimental group
Autologous ADRC transplantation in autoimmune refractory epilepsy
Biological: ADRC transplantation in autoimmune refractory epilepsy



Primary Outcome Measures :
  1. Rate of epileptic seizures [ Time Frame: 3 months ]
    recording of epileptic seizures frequency, EEG


Secondary Outcome Measures :
  1. Intelligence test [ Time Frame: 3 months ]
    The Leiter contains 10 subtests organized into four domains: Fluid Intelligence Visualization, Memory, Attention

  2. School progress [ Time Frame: 3 months ]
    teacher references


Other Outcome Measures:
  1. Radiological assesment [ Time Frame: 12 months ]
    MRI

  2. The level of antineural antibodies [ Time Frame: 3 months ]
    protein level, oligoclonal bands, IgG index as well as GluR3, VGKC complex/LGI1, GM1, NT-3, GAD, NMDAR antibodies from cerebrospinal fluid for evaluation the origin



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Drug-resistant epilepsy confirmed in anamnesis and diagnostic tests (EEG, MR)
  • Children between 3 and 18 years old
  • Presence of antineuronal antibody in serum or CSF
  • Rasmussen encephalitis (proven cellular immunity pathogenesis)
  • Probable autoimmune pathogenesis (autoimmune diseases in family, febrile infection associated refractory epilepsy)
  • Willing and able to provide written informed consent (patient or legal guardian)

Exclusion Criteria:

  • Refractory epilepsy with proven genetic or metabolic ethiology
  • Neoplastic disease
  • Active inflammatory process at the time of recruitment
  • Coagulation disorder
  • Status epilepticus
  • Participation in another clinical trial
  • Lack of willingness and ability to provide written informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03676569


Sponsors and Collaborators
Mossakowski Medical Research Centre Polish Academy of Sciences
Institution of Mother and Child, Warsaw, Poland
Investigators
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Principal Investigator: Dorota Antczak-Marach, M.D. Institute of Mother and Child
Principal Investigator: Ewa Sawicka, Prof. Institute of Mother and Child

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Responsible Party: Anna Sarnowska, M.D., Ph.D.; Head of Translative Platform for Regenerative Medicine MRC Mossakowski PAS, Mossakowski Medical Research Centre Polish Academy of Sciences
ClinicalTrials.gov Identifier: NCT03676569     History of Changes
Other Study ID Numbers: 17/2014 IMiD
First Posted: September 18, 2018    Key Record Dates
Last Update Posted: April 9, 2019
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Anna Sarnowska, Mossakowski Medical Research Centre Polish Academy of Sciences:
autoimmune epilepsy
refractory epilepsy
ADRC
mezenchymal stem cells
anti-neuronal antibody
Rasmussen encephality
adipose derived regenerative stem cells

Additional relevant MeSH terms:
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Epilepsy
Drug Resistant Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases