Refractory EpilepsyPhase 1EPIMSCNCT03676569
Intrathecal Autologous ADRC Treatment of Autoimmune Refractory Epilepsy
A Phase 1 study testing ADRC transplantation in autoimmune refractory epilepsy in people with Refractory Epilepsy, run by Mossakowski Medical Research Centre Polish Academy of Sciences.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Refractory Epilepsy
- What is being tested?
- ADRC transplantation in autoimmune refractory epilepsy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- No sites listed yet
- Study dates
- 15 Nov 2015to 14 Apr 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
About this study
Official title: 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.
Read the 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.
- Conditions
- Refractory Epilepsy
- Being tested
- ADRC transplantation in autoimmune refractory epilepsy
- Keywords
- autoimmune epilepsy, refractory epilepsy, ADRC, mezenchymal stem cells, anti-neuronal antibody, Rasmussen encephality, adipose derived regenerative stem cells
- Medical subject headings
- Drug Resistant Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ADRC transplantation in autoimmune refractory epilepsyBiological
| Study group | Role | What they receive |
|---|---|---|
| Experimental group | Experimental | Autologous ADRC transplantation in autoimmune refractory epilepsy Receives: Biological: ADRC transplantation in autoimmune refractory epilepsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of epileptic seizures
recording of epileptic seizures frequency, EEG
Measured: 3 months
Secondary outcomes (2)
Intelligence test
The Leiter contains 10 subtests organized into four domains: Fluid Intelligence Visualization, Memory, Attention
Measured: 3 months
School progress
teacher references
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2018
- Study start15 Nov 2015
- Primary completion14 Apr 2019
- Study completion14 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Refractory EpilepsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Experimental clinical treatment
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mossakowski Medical Research Centre Polish Academy of Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Institute of Mother and Child, Warsaw, Poland
- Responsible party
- Principal investigator, Anna Sarnowska, Mossakowski Medical Research Centre Polish Academy of Sciences
- Investigators
- Dorota Antczak-Marach, M.D., Principal investigator, Institute of Mother and ChildEwa Sawicka, Prof., Principal investigator, Institute of Mother and Child
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03676569
- Sponsor's protocol ID
- 17/2014 IMiD
- Acronym
- EPIMSC
- Status last verified
- Apr 2020
- First submitted
- 14 Sep 2018
- Last updated
- 15 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 32190059
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intrathecal Autologous Adipose Derived Regenerative Cells Treatment of Autoimmune Determined Refractory Epilepsy - Evaluation of Safety and Efficacy
- ClinicalTrials.gov ID
- NCT03676569
- Acronym / sponsor ID
- EPIMSC / 17/2014 IMiD
- Conditions
- Refractory Epilepsy
- Keywords
- autoimmune epilepsy, refractory epilepsy, ADRC, mezenchymal stem cells, anti-neuronal antibody, Rasmussen encephality, adipose derived regenerative stem cells
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Mossakowski Medical Research Centre Polish Academy of SciencesUniversity, hospital or other
- Collaborators
- Institute of Mother and Child, Warsaw, Poland
- Study start
- 15 Nov 2015 (actual)
- Primary completion
- 14 Apr 2019 (actual)
- Study completion
- 14 Apr 2019 (actual)
- First posted
- 18 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Experimental clinical treatment
| Arm | Type | Receives |
|---|---|---|
| Experimental group | Experimental | Biological: ADRC transplantation in autoimmune refractory epilepsyAutologous ADRC transplantation in autoimmune refractory epilepsy |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (7 listed)
- Refractory epilepsy with proven genetic or metabolic ethiology
- Neoplastic disease
- Active inflammatory process at the time of recruitment
- Coagulation disorder
- Status epilepticus
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ADRC transplantation in autoimmune refractory epilepsy | Biological | Experimental group |
Primary outcome
Rate of epileptic seizures
Time frame: 3 months
recording of epileptic seizures frequency, EEG
2 secondary outcomes
Intelligence test
Time frame: 3 months
School progress
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2020.
- Results publication: PubMed 32190059Szczepanik 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dorota Antczak-Marach, M.D. principal investigator
Institute of Mother and Child
Ewa Sawicka, Prof. principal investigator
Institute of Mother and Child
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ADRC transplantation in autoimmune refractory epilepsy in people with Refractory Epilepsy, run by Mossakowski Medical Research Centre Polish Academy of Sciences.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of epileptic seizures (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03676569, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2020.