Safety of Autologous MSC Infusion to Treat Epilepsy

NCT02497443 | Completed Phase 1

• 1 other identifier: Minsk-MH001
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

• The goal of this study was to evaluate the safety and efficacy of autologous MSC application for the therapy of drug-resistant symptomatic epilepsy. Adult (18-60 years old) patients (pts) of both sexes suffering from refractory epilepsy with frequent (\>5 events per month) seizures were included in this study. The pts were randomized to the standard treatment with anti-epileptic drugs (control group, 30 pts) or anti-epileptic drugs plus autologous mesenchymal stem cells (MSCs) (study group, 30 pts). The pts in the study group received one intravenous injection of ex vivo expanded MSCs (40-101 x 106 cells) and one subsequent endolumbal injection of neuroinduced MSCs (2.7 - 8.0 x 106 cells). Both the unfavorable reactions to MSC infusions and the clinical effects, including complications, were examined. The unfavorable reactions to the MSC injections included local pain or hemorrhage at the site of injection and systemic reactions of the central nervous system (CNS; i.e., hyperthermia, fatigue, and myalgia).The possible beneficial effects of therapy in the two groups of pts were examined based on clinical observations and electroencephalography measurements (prior and 12 months after the application of the MSC-based therapy). To determine potential changes in disease progression, the signs of cognitive impairment, behavioral disorders, and particularly, changes in seizure character and frequency were evaluated using the National Hospital Scale of Seizure Severity. The main points of disease monitoring were "yes" or "no" responses (to therapy), seizure frequency (per month), and remission of disease. Electroencephalography (EEG) recordings were performed to evaluate electrical alpha, beta, theta and delta waves based on standard and additional criteria. The paroxismality index, the peak frequency of EEG activity, the index of slow activity, and the summarized points of EEG pathology signs were calculated for each patient. All assessments were performed for the pts in the control and study groups, and the obtained data were compared to identify the potential differences between the two pts groups. Therapy was terminated when immediate unfavorable reactions to the MSC injections were observed. The final observation of each patient included clinical and EEG assessments at the time point of 12 months (or more) after the application of the MSC-based therapy.

Conditions

Epilepsy

Keywords

drug-resistant symptomatic epilepsy; seizure; autologous mesenchymal stem cells; safety; remission; electroencephalography; refractory symptomatic epilepsy; autologous MSC; efficacy

Outcome Measures

Primary Outcomes (1)

• Safety of autologous bone marrow-derived Mesenchymal Stem Cells in patients with Drug-Resistant Symptomatic Epilepsy

  * vital signs * adverse events related to infusion * physical examination indexes

  360 days

Secondary Outcomes (1)

• Efficacy of autologous bone marrow-derived Mesenchymal Stem Cells in patients with Drug-Resistant Symptomatic Epilepsy

  360 days

Study Arms (2)

study group

EXPERIMENTAL

Pts undergoing carbamazepine, valproic acid, topiramate, lamotrigine, or phenobarbital (i.e.anti-epileptic drugs \[AEDs\]) and receiving autologous mesenchymal stem cells

Biological: Autologous mesenchymal stem cells

control group

NO INTERVENTION

Pts undergoing carbamazepine, valproic acid, topiramate, lamotrigine, or phenobarbital (i.e.AEDs)

Interventions

Autologous mesenchymal stem cells BIOLOGICAL

Autologous bone marrow-derived mesenchymal stem cells, expanded ex vivo and neuroinduced (a portion of the cells). The final autologous cultured MSCs (0.7 -1.4 x 106 cells/kg of weigh) and autologous neuroinduced MSCs (0.04 - 0.1 x 106 cells/kg of weigh) were used for intravenous administration (cultured MSCs) and a subsequent endolumbal injection (neuroinduced MSCs) one week later in the patients in an autologous manner.

study group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Clinical diagnosis of symptomatic epilepsy,
• Disease progression for the last 1-3 years,
• Resistance of epilepsy to therapy with carbamazepine, valproic acid, topiramate, lamotrigine, and phenobarbital (anti-epileptic drugs/AEDs) as monotherapies or combination therapies;
• Signed informed consent

You may not qualify if:

• Central nervous system inflammatory disorders (meningoencephalitis of viral or parasite origin),
• Chronic decompensated psychoses ,dementia, social disadaptation,
• Central nervous system tumours.
• Blood positivity for hepatitis B or C or HIV infection;
• According to the judgment of the researchers, subjects who were unable to complete the study or may not have been able to comply with the requirements of this study (due to administrative or other reasons).

Sponsors & Collaborators

• Ministry of Public Health, Republic of Belarus: lead

Related Publications (5)

• O'Donoghue MF, Duncan JS, Sander JW. The subjective handicap of epilepsy. A new approach to measuring treatment outcome. Brain. 1998 Feb;121 ( Pt 2):317-43. doi: 10.1093/brain/121.2.317.

  PMID: 9549509 BACKGROUND

• Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361-70. doi: 10.1111/j.1600-0447.1983.tb09716.x.

  PMID: 6880820 BACKGROUND

• Shakhbazau AV, Goncharova NV, Kosmacheva SM, Kartel' NA, Potapnev MP. Plasticity of human mesenchymal stem cell phenotype and expression profile under neurogenic conditions. Bull Exp Biol Med. 2009 Apr;147(4):513-6. doi: 10.1007/s10517-009-0547-6. English, Russian.

  PMID: 19704961 BACKGROUND

• Hlebokazov F, Dakukina T, Potapnev M, Kosmacheva S, Moroz L, Misiuk N, Golubeva T, Slobina E, Krasko O, Shakhbazau A, Hlavinski I, Goncharova N. Clinical benefits of single vs repeated courses of mesenchymal stem cell therapy in epilepsy patients. Clin Neurol Neurosurg. 2021 Aug;207:106736. doi: 10.1016/j.clineuro.2021.106736. Epub 2021 Jun 8.

  PMID: 34119901 DERIVED

• Hlebokazov F, Dakukina T, Ihnatsenko S, Kosmacheva S, Potapnev M, Shakhbazau A, Goncharova N, Makhrov M, Korolevich P, Misyuk N, Dakukina V, Shamruk I, Slobina E, Marchuk S. Treatment of refractory epilepsy patients with autologous mesenchymal stem cells reduces seizure frequency: An open label study. Adv Med Sci. 2017 Sep;62(2):273-279. doi: 10.1016/j.advms.2016.12.004. Epub 2017 May 10.

  PMID: 28500900 DERIVED

MeSH Terms

Conditions

Epilepsy; Seizures

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Tatiana V Dakukina, MD,PhD

  Deputy Director for Research, Republican Scientific and Practical Center for Mental Health, Minsk, Belarus

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: Masking was specified as Opel Label study in old format
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head the Department of Cellular BioTechnologies, Republican Scientific and Practical Center of Transfusiology and Medical Biotechnologies

Study Record Dates

• First Submitted: April 7, 2015
• First Posted: July 14, 2015
• Study Start: April 1, 2011
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2019
• Last Updated: April 5, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Final Record and accepted data base of participants wil become available after finalization of study and will be available for one year
• Access Criteria: Access will be available for physicians and researches, specialized in biomedical studies