Intranasal Inhalations of Bioactive Factors Produced by M2 Macrophages in Patients With Organic Brain Syndrome

NCT02957123 | Completed Phase 1 Results

• 1 other identifier: IFCI-25/05/2015
• Study Type: interventional
• Target: 30
• 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 treatment/rehabilitation efficacy and functional outcome of patients with organic brain syndrome are improved with intranasal inhalations of bioactive factors (BF), produced by autologous M2 macrophages (auto-M2-BFs). The rationale for this approach is the ability of central nervous system to repair and the important role of macrophages in the regulation of this process. It was found that type 2 macrophages have anti-inflammatory and reparative potential, whereas M1 cells possess pro-inflammatory and neurotoxic effects. Action of M2 macrophages is largely realized through the production a wide variety 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 auto-M2-BFs, as therapeutic agents and intranasal administration focusing on nose to brain transport, as a mode of delivery. Expected clinical effects in treated subjects: improvement of cognitive functions (memory, language, attention); correction of focal neurological deficit (paresis, spasticity, sensory disorders); reduction vestibular/ataxic disorders (vertigo, unsteadiness when walking); reduction of headaches; reduction of asthenia (weakness, fatigue); correction of emotional disorders (anxiety, depression).

Conditions

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

Keywords

macrophages M2 type; cytokines; intranasal administration; neuroprotection; neuroregeneration; organic brain syndrome; neurocognitive disorders

Outcome Measures

Primary Outcomes (1)

• The Number of Patients With Severe Adverse Events and Adverse Reactions

  Occurrence of severe adverse events and adverse reactions (allergic, toxic, inflammatory reactions; neurological deterioration, convulsive syndrome)

  up to 6 months after treatment

Secondary Outcomes (4)

• Change in Subjective Assessment of Clinical Symptoms (SACS)

  Baseline and 6 months after treatment

• Change in Hospital Anxiety and Depression Scale (HADS)

  Baseline and 6 months after treatment

• Change in Functional Mobility Assessment (FMA) Scale

  Baseline and 6 months after treatment

• Change in Montreal Cognitive Assessment (МоСА)

  Baseline and 6 months after treatment

Study Arms (1)

Intranasal auto-M2-BFs

EXPERIMENTAL

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. 30 patients with organic brain syndrome will receive auto-M2-BFs with the aerosol inhaler device (nebulizer), 2.0 mL once a day up to 30 days.

Drug: Intranasal auto-M2-BFs

Interventions

Intranasal auto-M2-BFs DRUG

Delivery is performed with the aerosol inhaler device (nebulizer), 2.0 mL once a day up to 30 days.

Also known as: Bioactive Factors, Produced by M2 Macrophage

Intranasal auto-M2-BFs

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults: age 18 - 80
• Persistent neurological deficits (cognitive, mental, motor, vestibular/ataxic disorders as a result of trauma, cardiovascular, neurodegenerative and others cerebral injuries), confirmed clinically and by CT or MRI
• A written informed consent of the patient or close relatives

You may not qualify if:

• Psychiatric disorders
• Seizures
• Severe dementia
• Hepatic or renal dysfunctions
• Hemodynamic or respiratory instability
• HIV or uncontrolled bacterial, fungal, or viral infections
• Pregnancy
• Malignancy
• 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)

• Chernykh ER, Shevela EY, Sakhno LV, Tikhonova MA, Petrovsky YL, Ostanin AA. The generation and properties of human M2-like macrophages: potential candidates for CNS repair? Cell Ther Transplant., 2010 DOI: 10.3205/ctt-2010-en-000080.01

  BACKGROUND

• 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 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 EY., Davydova MN, Starostina NM, Yankovskaya AA, Ostanin AA, Chernykh ER. Intranasal delivery of M2 macrophage-derived soluble products reduces neurological deficit in patients with cerebrovascular disease: A Pilot Study. Journal of Neurorestoratology, 2019; 7: 89-100 doi:10.26599/JNR.2019.9040010

  RESULT

MeSH Terms

Conditions

Neurocognitive Disorders; Chronic Traumatic Encephalopathy; Brain Ischemia

Condition Hierarchy (Ancestors)

Mental Disorders; Brain Injuries, Traumatic; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Injury, Chronic; Neurodegenerative Diseases; Craniocerebral Trauma; Trauma, Nervous System; Brain Damage, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Wounds and Injuries; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Alexander A Ostanin, MD, PhD
• Organization: Institute of Fundamental and Clinical Immunology

ostanin62@mail.ru

+7 (383) 236-03-29

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

Publication Agreements

• PI is Sponsor Employee: Yes

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: November 3, 2016
• First Posted: November 7, 2016
• Study Start: March 1, 2016
• Primary Completion: September 1, 2020
• Study Completion: September 1, 2020
• Last Updated: February 18, 2021
• Results First Posted: February 18, 2021

Record last verified: 2021-02

Locations

RU (1)