Intranasal Inhalations of M2 Macrophage Soluble Factors in Children With Developmental Speech Disorders

NCT04689282 | Completed Phase 1

• 1 other identifier: IFCI-23/06/2017
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators have designed an innovative proof-of-concept trial designed to provide data as to whether the speech difficulties in children with developmental dysphasia (DD) are improved with intranasal inhalations of bioactive factors (BF), produced by macrophages of M2 phenotype (M2-BFs). The rationale for this approach is the ability of central nervous system (CNS) to repair and the important role of macrophages in the regulation of this process. It was found that type 2 macrophages (M2) have anti-inflammatory and neurorestorative potential, in contrast to pro-inflammatory and neurotoxic effects of М1 cells. The influence of M2 is largely realized through the production of a wide spectrum of bioactive factors (cytokines, chemokines, growth factors, neuropeptides, microvesicles etc) that inhibit inflammation, protect neurons from apoptosis, stimulate neurogenesis, the growth and remyelination of axons, the formation of new synapses and activate angiogenesis. This study uses M2-BFs, as therapeutic tool, and intranasal administration focusing on nose to brain transport, as a mode of delivery. Expected clinical effects in treated children: improvement of speech understanding, word formation, grammatical structure of speech and formation of coherent speech.

Conditions

Language Delay; Language; Developmental Disorder, Expressive; Language; Developmental Disorder, Receptive; Autism Spectrum Disorder; Attention Deficit-Hyperactivity Disorder; Speech Disorders in Children

Keywords

M2 type macrophages; Cytokines; Intranasal administration; Neuroprotection; neuroregeneration; Speech disorders

Outcome Measures

Primary Outcomes (1)

• Change in the severity of speech disorders according to Speech Assessment Scale (SAS)

  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.

  Baseline and 6 months after treatment

Secondary Outcomes (1)

• The number of patients with adverse events

  up to 6 months after treatment

Study Arms (1)

Intranasal M2-BFs

EXPERIMENTAL

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).

Interventions

Bioactive Factors, Produced by M2 Type Macrophages (M2-BFs). BIOLOGICAL

Intranasal delivery of M2-BFs is performed with the aerosol inhaler device (nebulizer), 2.0 mL once a day up to 30 days.

Intranasal M2-BFs

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 3-18
• Speech disorders verified by speech therapist and neurologist
• Adequate hearing/vision to follow conversation
• Russian speaker
• A written informed consent of the parents/close relatives

You may not qualify if:

• Acute infectious disease (bacterial, fungal, or viral)
• Seizures
• Intolerance to gentamicin and/or multiple drug allergies
• Participation in other clinical trials

Sponsors & Collaborators

• Russian Academy of Medical Sciences: lead

Study Sites (1)

Institute of Fundamental and Clinical Immunology

Novosibirsk, 630099, Russia

Location

Related Publications (5)

• Sakhno LV, Shevela EY, Tikhonova MA, Ostanin AA, Chernykh ER. The Phenotypic and Functional Features of Human M2 Macrophages Generated Under Low Serum Conditions. Scand J Immunol. 2016 Feb;83(2):151-9. doi: 10.1111/sji.12401.

  PMID: 26678544 BACKGROUND

• Chernykh ER, Kafanova MY, Shevela EY, Sirota SI, Adonina EI, Sakhno LV, Ostanin AA, Kozlov VV. Clinical experience with autologous M2 macrophages in children with severe cerebral palsy. Cell Transplant. 2014;23 Suppl 1:S97-104. doi: 10.3727/096368914X684925. Epub 2014 Oct 9.

  PMID: 25302537 BACKGROUND

• Chernykh ER, Shevela EYa, Kafanova MYu, Sakhno LV, Polovnikov EV, Ostanin AA. Monocyte-derived macrophages for treatment of cerebral palsy: a study of 57 cases. J Neurorestoratology. 2018; 6: 41-47. doi.org/10.2147/JN.S158843

  BACKGROUND

• Chernykh ER, Shevela EY, Starostina NM, Morozov SA, Davydova MN, Menyaeva EV, Ostanin AA. Safety and Therapeutic Potential of M2 Macrophages in Stroke Treatment. Cell Transplant. 2016;25(8):1461-71. doi: 10.3727/096368915X690279. Epub 2015 Dec 14.

  PMID: 26671426 BACKGROUND

• Shevela E, Davydova M, Starostina N, Yankovskaya A, Ostanin A, Chernykh E. Intranasal delivery of M2 macrophage-derived soluble products reduces neuropsychological deficit in patients with cerebrovascular disease: a pilot study. J Neurorestoratology. 2019; 7: 89-100. doi:10.26599/JNR.2019.9040010

  BACKGROUND

Related Links

• Shevela E.Y., et al. Therapeutic effect of soluble factors of M2 phenotype macrophages in children with language impairments. Medical Immunology (Russia). 2021;23(5):1137-1150. (In Russ.) https://doi.org/10.15789/1563-0625-TEO-2224

MeSH Terms

Conditions

Language Development Disorders; Language; Developmental Disabilities; Autism Spectrum Disorder; Attention Deficit Disorder with Hyperactivity; Speech Disorders

Condition Hierarchy (Ancestors)

Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Communication; Behavior; Neurodevelopmental Disorders; Mental Disorders; Child Development Disorders, Pervasive; Attention Deficit and Disruptive Behavior Disorders

Study Officials

• Elena R Chernykh, MD, PhD

  Institute of Fundamental and Clinical Immunology

  STUDY CHAIR

• Alexander A Ostanin, MD, PhD

  Institute of Fundamental and Clinical Immunology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Clinical Department

Study Record Dates

• First Submitted: December 23, 2020
• First Posted: December 30, 2020
• Study Start: February 1, 2020
• Primary Completion: September 1, 2021
• Study Completion: September 1, 2021
• Last Updated: May 2, 2022

Record last verified: 2022-04

Locations

RU (1)