Intranasal Inhalations of M2 Macrophage Soluble Factors in Children With Developmental Speech Disorders
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|ClinicalTrials.gov Identifier: NCT04689282|
Recruitment Status : Recruiting
First Posted : December 30, 2020
Last Update Posted : December 30, 2020
|Condition or disease||Intervention/treatment||Phase|
|Language Delay Language; Developmental Disorder, Expressive Language; Developmental Disorder, Receptive Autism Spectrum Disorder Attention Deficit-Hyperactivity Disorder Speech Disorders in Children||Biological: Bioactive Factors, Produced by M2 Type Macrophages (M2-BFs).||Phase 1 Phase 2|
Neuroinflammation plays a central role in the pathogenesis of any damage to the central nervous system (CNS) profoundly affecting the ability of neural cells to survive and to regenerate. Macrophages play a key role in the regulation of neuroinflammation, but their role is ambiguous. In fact, macrophages can both induce neuronal and glial toxicity and promote tissue repair. The opposite effects of macrophages are largely due to their plasticity and functional heterogeneity. Thus, classical pro-inflammatory macrophages (M1) are tissue-destructive, while anti-inflammatory (M2) macrophages mediate tissue repair. In addition, M2 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 . The data indicate that M2, in contrast to pro-inflammatory M1, 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 high IL-10 level. M2 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.
Pilot clinical trials have demonstrated the safety and clinical efficacy of intrathecal administration of M2 in children with severe cerebral palsy [2, 3] and in nonacute stroke patients . Moreover, intranasal delivery of M2 macrophage-derived soluble products reduces neuropsychological deficit in patients with cerebrovascular disease . Given this data, the investigators expect that intranasal administration of the M2-BFs (Bioactive Factors) will reduce the severity of speech disorders in children, including improving speech understanding, sensorimotor speech level, word formation skills, as well as the formation of the grammatical structure of speech and coherent speech. Of note, intranasal administration of M2 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 :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Safety/Efficacy of Intranasally-Administered Bioactive Factors Produced by M2 Type Macrophages in Children With Developmental Speech Disorders|
|Actual Study Start Date :||February 1, 2020|
|Estimated Primary Completion Date :||December 1, 2021|
|Estimated Study Completion Date :||July 1, 2022|
Experimental: Intranasal M2-BFs
Intranasally-Administered Bioactive Factors, Produced by M2 Type Macrophages (M2-BFs). M2 were generated in vitro from peripheral blood of a parent during 7 days. Cell-free culture medium, containing M2-BFs, was collected, and aliquots of 2 mL/vial were cryopreserved.
30 children with speech disorders will receive their first doses (n=2-3) of 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.
Biological: Bioactive Factors, Produced by M2 Type Macrophages (M2-BFs).
Intranasal delivery of M2-BFs is performed with the aerosol inhaler device (nebulizer), 2.0 mL once a day up to 30 days.
- Change in the severity of speech disorders according to Speech Assessment Scale (SAS) [ Time Frame: Baseline and 6 months after treatment ]Speech Assessment Scale (SAS) is used to assess language development in children in six functional domains: Speech Comprehension; Sensomotor speech level; Grammatical structure of speech and inflection; Vocabulary and vocabulary skills; Connected speech; Gross and fine motor skills. Max total score:160 points (units of scale). Clinical improvement is manifested in an enhancement in the SAS score.
- 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
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): NCT04689282
|Contact: Valentina G Degtyareva, PhD||+7 (383) firstname.lastname@example.org|
|Contact: Ekaterina Y Shevela, MD, PhD||+7 (383) email@example.com|
|Institute of Fundamental and Clinical Immunology||Recruiting|
|Novosibirsk, Russian Federation, 630099|
|Contact: Elena R Chernykh, MD, PhD +7 (383) 236-03-29 firstname.lastname@example.org|
|Contact: Alexander A Ostanin, MD, PhD +7 (383) 236-03-29 email@example.com|
|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|