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Intrathecal Autologous ADRC Treatment of Autoimmune Refractory Epilepsy (EPIMSC)

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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

Tracking Information
First Submitted Date  ICMJE September 14, 2018
First Posted Date  ICMJE September 18, 2018
Last Update Posted Date April 9, 2019
Actual Study Start Date  ICMJE November 15, 2015
Estimated Primary Completion Date November 10, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 17, 2018)
Rate of epileptic seizures [ Time Frame: 3 months ]
recording of epileptic seizures frequency, EEG
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03676569 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 7, 2019)
  • Intelligence test [ Time Frame: 3 months ]
    The Leiter contains 10 subtests organized into four domains: Fluid Intelligence Visualization, Memory, Attention
  • School progress [ Time Frame: 3 months ]
    teacher references
Original Secondary Outcome Measures  ICMJE
 (submitted: September 17, 2018)
  • Psychological state [ Time Frame: 3 months ]
    Leiter International Performance Scale
  • School progress [ Time Frame: 3 months ]
    teacher references
Current Other Pre-specified Outcome Measures
 (submitted: September 17, 2018)
  • Radiological assesment [ Time Frame: 12 months ]
    MRI
  • 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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Intrathecal Autologous ADRC Treatment of Autoimmune Refractory Epilepsy
Official Title  ICMJE Intrathecal Autologous Adipose Derived Regenerative Cells Treatment of Autoimmune Determined Refractory Epilepsy - Evaluation of Safety and Efficacy
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
Experimental clinical treatment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Refractory Epilepsy
Intervention  ICMJE Biological: ADRC transplantation in autoimmune refractory epilepsy
Study Arms  ICMJE Experimental: Experimental group
Autologous ADRC transplantation in autoimmune refractory epilepsy
Intervention: Biological: ADRC transplantation in autoimmune refractory epilepsy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: September 17, 2018)
6
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 10, 2019
Estimated Primary Completion Date November 10, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03676569
Other Study ID Numbers  ICMJE 17/2014 IMiD
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Anna Sarnowska, Mossakowski Medical Research Centre Polish Academy of Sciences
Study Sponsor  ICMJE Mossakowski Medical Research Centre Polish Academy of Sciences
Collaborators  ICMJE Institution of Mother and Child, Warsaw, Poland
Investigators  ICMJE
Principal Investigator: Dorota Antczak-Marach, M.D. Institute of Mother and Child
Principal Investigator: Ewa Sawicka, Prof. Institute of Mother and Child
PRS Account Mossakowski Medical Research Centre Polish Academy of Sciences
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP