Clinical trial NCT03676569: Intrathecal Autologous ADRC Treatment of Autoimmune Refractory Epilepsy
Official title: Intrathecal Autologous Adipose Derived Regenerative Cells Treatment of Autoimmune Determined Refractory Epilepsy - Evaluation of Safety and Efficacy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Refractory Epilepsy
Keywords: autoimmune epilepsy
refractory epilepsy
ADRC
mezenchymal stem cells
anti-neuronal antibody
Rasmussen encephality
adipose derived regenerative stem cells
Lead sponsor: Mossakowski Medical Research Centre Polish Academy of Sciences
Sponsor class: OTHER
Collaborators: name: Institute of Mother and Child, Warsaw, Poland
First posted: 2018-09-18
Enrollment: 6
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Experimental clinical treatment
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Rate of epileptic seizures
timeFrame: 3 months
Secondary outcomes:
measure: Intelligence test
timeFrame: 3 months
measure: School progress
timeFrame: 3 months
Other outcomes:
measure: Radiological assesment
timeFrame: 12 months
measure: The level of antineural antibodies
timeFrame: 3 months
Locations:
Study officials:
affiliation: Institute of Mother and Child
name: Dorota Antczak-Marach, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Mother and Child
name: Ewa Sawicka, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.