Intrathecal Autologous ADRC Treatment of Autoimmune Refractory Epilepsy (EPIMSC)

Intrathecal Autologous Adipose Derived Regenerative Cells Treatment of Autoimmune Determined Refractory Epilepsy - Evaluation of Safety and Efficacy

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.

Study Overview

• Status: Completed
• Conditions: Refractory Epilepsy
• Intervention / Treatment: Biological: ADRC transplantation in autoimmune refractory epilepsy

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: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Experimental group; Autologous ADRC transplantation in autoimmune refractory epilepsy	Biological: ADRC transplantation in autoimmune refractory epilepsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of epileptic seizures	recording of epileptic seizures frequency, EEG	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intelligence test	The Leiter contains 10 subtests organized into four domains: Fluid Intelligence Visualization, Memory, Attention	3 months
School progress	teacher references	3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiological assesment	MRI	12 months
The level of antineural antibodies	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	3 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Szczepanik E, Mierzewska H, Antczak-Marach D, Figiel-Dabrowska A, Terczynska I, Tryfon J, Krzesniak N, Noszczyk BH, Sawicka E, Domanska-Janik K, Sarnowska A. Intrathecal Infusion of Autologous Adipose-Derived Regenerative Cells in Autoimmune Refractory Epilepsy: Evaluation of Safety and Efficacy. Stem Cells Int. 2020 Jan 3;2020:7104243. doi: 10.1155/2020/7104243. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 15, 2015
• Primary Completion (ACTUAL): April 14, 2019
• Study Completion (ACTUAL): April 14, 2019

Study Registration Dates

• First Submitted: September 14, 2018
• First Submitted That Met QC Criteria: September 17, 2018
• First Posted (ACTUAL): September 18, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 15, 2020
• Last Update Submitted That Met QC Criteria: April 14, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: ADRC; refractory epilepsy; autoimmune epilepsy; mezenchymal stem cells; anti-neuronal antibody; Rasmussen encephality; adipose derived regenerative stem cells
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Drug Resistant Epilepsy
• Other Study ID Numbers: 17/2014 IMiD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No