Intranasal Inhalations of Bioactive Factors Produced by M2 Macrophages in Patients With Organic Brain Syndrome
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|ClinicalTrials.gov Identifier: NCT02957123|
Recruitment Status : Recruiting
First Posted : November 7, 2016
Last Update Posted : November 8, 2017
|Condition or disease||Intervention/treatment||Phase|
|Organic Brain Syndrome, Nonpsychotic Neurocognitive Disorders Mental Disorder, Organic Delirium, Dementia, Amnestic, Cognitive Disorders Nonpsychotic Organic Brain Syndrome Organic Mental Disorder Encephalopathy, Post-Traumatic, Chronic Encephalopathy, Ischemic Brain Ischemia||Drug: Intranasal auto-M2-BFs||Phase 1 Phase 2|
Following injury to the central nervous system (CNS), immune-mediated inflammation profoundly affects the ability of neural cells to survive and to regenerate. The role of inflammation comprises mostly of macrophages, is controversial, since macrophages can both induce neuronal and glial toxicity and promote tissue repair. The opposite effects of macrophages may be conditioned by their functional heterogeneity. Thus, classical pro-inflammatory macrophages (M1) are tissue-destructive, while anti-inflammatory (M2) macrophages mediate tissue repair. In addition, M2 macrophages predominantly induce the Th2 response, which is particularly beneficial in CNS repair. Using low serum conditions the investigators have generated M2-like macrophages and evaluated their phenotypic and functional features [1, 2]. Our data indicate that M2 macrophages, in contrast to pro-inflammatory M1 cells, produced significantly lower levels of pro-inflammatory cytokines (IL-1β, tumor necrosis factor-α, IL-6, IL-18, IL-12), chemokines (IL-8, monocyte chemoattractant protein 1-1) and Th1/Th2-cytokines (interferon-γ, IL-2, IL-4) coupled with a higher IL-10 level. M2 macrophages were capable of producing neurotrophic- (brain-derived neurotrophic factor,insulin-like growth factor-1), angiogenic- (vascular endothelial growth factor), and other growth factors (erythropoietin, granulocyte-colony stimulating factor , basic fibroblast growth factor, epidermal growth factor) with neuroprotective and regenerative activity.
Our pilot clinical trials have demonstrated the safety and clinical efficacy of intrathecal administration of M2 macrophages in children with severe cerebral palsy  and in non-acute stroke patients .
Since cell-free culture medium of M2 macrophages contains a wide variety of neurotrophic, immunoregulatory and pro-angiogenic factors, the investigators expect that intranasal administration of these auto-M2-BFs will improve the treatment/rehabilitation efficacy and functional outcome of patients with organic brain syndrome. Of note, intranasal administration of M2-macrophage soluble factors allow to delivery bioactive agents to brain through the olfactory and trigeminal ways across brain-blood barrier.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Safety/Efficacy of Intranasally-Administered Bioactive Factors Produced by Autologous M2 Macrophages in Patients With Organic Brain Syndrome|
|Actual Study Start Date :||March 2016|
|Estimated Primary Completion Date :||November 2020|
|Estimated Study Completion Date :||May 2021|
Experimental: Intranasal auto-M2-BFs
Intranasally-Administered Bioactive Factors, Produced by Autologous M2 Macrophage (auto-M2-BFs). M2 macrophages were generated in vitro from peripheral blood of patients during 7 days.Cell-free culture medium, containing auto-M2-BFs, was collected and aliquots of 2 mL/vial were cryopreserved.
60 patients with organic brain syndrome will receive their first doses (n=2-3) of auto-M2-BFs in clinic and wait 2 hrs to determine any short-time adverse effects of inhaled dose.
The subsequent course of intranasal inhalations (once a day up to 30 days) performed as outpatient treatment.
Drug: Intranasal auto-M2-BFs
Delivery is performed with the aerosol inhaler device (nebulizer), 2.0 mL once a day up to 30 days.
Other Name: Bioactive Factors, Produced by M2 Macrophage
- The number of patients with adverse events [ Time Frame: up to 6 months after treatment ]Occurrence of adverse events including allergic, toxic, inflammatory reactions; neurological worsening; seizures
- Change in neurological status [ Time Frame: Baseline, 4 weeks and 6 months after treatment ]
- Change in National Institutes of Health Stroke Scale (NIHSS) for post-stroke patients [ Time Frame: Baseline, 4 weeks and 6 months after treatment ]
- Change in Barthel ADL index [ Time Frame: Baseline, 4 weeks and 6 months after treatment ]
- Change in Instrumental Activities of Daily Living (IADL) scale [ Time Frame: Baseline, 4 weeks and 6 months after treatment ]
- Change in Basic Activities of Daily Living scale [ Time Frame: Baseline, 4 weeks and 6 months after treatment ]
- Change in Hospital Anxiety and Depression scale (HAD) [ Time Frame: Baseline, 4 weeks and 6 months after treatment ]
- Change in Modified Ashworth Scale of Muscle Spasticity [ Time Frame: Baseline, 4 weeks and 6 months after treatment ]
- Change in Montreal Cognitive Assessment (МоСА) [ Time Frame: Baseline, 4 weeks and 6 months after treatment ]
- Change in Performance Oriented Mobility Assessment (POMA) [ Time Frame: Baseline, 4 weeks and 6 months after treatment ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02957123
|Contact: Natalia M Starostina, PhD||+7 (383) email@example.com|
|Contact: Mariya N Davydova||+7 (383) firstname.lastname@example.org|
|Institute of Fundamental and Clinical Immunology||Recruiting|
|Novosibirsk, Russian Federation, 630099|
|Contact: Elena R Chernykh, MD, PhD +7 (383) 236-03-29 email@example.com|
|Contact: Alexander A Ostanin, MD, PhD +7 (383) 236-03-29 firstname.lastname@example.org|
|Study Chair:||Elena R Chernykh, MD, PhD||Institute of Fundamental and Clinical Immunology|
|Principal Investigator:||Alexander A Ostanin, MD, PhD||Institute of Fundamental and Clinical Immunology|