The Pilot Experimental Study of the Neuroprotective Effects of Exosomes in Extremely Low Birth Weight Infants

NCT05490173 | Not Yet Recruiting DMC

• 1 other identifier: ncagp4382277
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

To study the safety and efficacy of intranasal administration of exosomes derived from mesenchymal stromal cells on long-term neurodevelopmental outcome in extremely low birth weight infants born at gestational age 25/0-27/6 weeks.

Conditions

Premature Birth; Extreme Prematurity; Preterm Intraventricular Hemorrhage; Hypoxia-Ischemia, Cerebral; Neurodevelopmental Disorders

Keywords

Extremely low birth weight, neuroprotection

Outcome Measures

Primary Outcomes (1)

• Occurrence and rate of dose limiting toxicity

  Dose limiting toxicity consists of the following events: Death occurring within 24 hours after intranasal administration of EVs; Hypersensitivity / anaphylactic to EVs defined as any severe systemic inflammatory response syndrome with negative blood culture not consistent with the overall clinical course of the infant occurring within 72 hours after intranasal administration of EVs; Any other serious adverse event not expected in this patient population for which there is no alternative explanation but the administration of EVs, occurring within 1 week of injection.

  Up to 1 week following after intranasal administration of EVs

Secondary Outcomes (10)

• Rate of death

  From enrollment until discharge or 40 weeks corrected gestational age (whichever occurs first)

• Occurrence of Other Severe Complications of Prematurity

  From enrollment until discharge or 40 weeks corrected gestational age (whichever occurs first)

• Need for Ventilatory Support

  From enrollment until discharge, 40 weeks corrected gestational age, or death (whichever occurs first)

• Changes in Hemodynamics

  Time Frame: At enrollment, 48 hours following intranasal administration of EVs, 28 days of life, and 36 weeks corrected gestational age

• Feasibility: Administration

  Day of life 1-10

Study Arms (2)

Intranasal exosomes administration

EXPERIMENTAL

ELWB newborns who will receive intranasal exosomes

Other: Exosomes derived from mesenchymal stromal cells (MSCs)

Control

NO INTERVENTION

ELWB newborns who will not receive intranasal exosomes

Interventions

Exosomes derived from mesenchymal stromal cells (MSCs) OTHER

Exosomes derived from mesenchymal stromal cells (MSCs) will be administered intranasal in ELBW infants

Intranasal exosomes administration

Eligibility Criteria

• Age: 1 Day - 3 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Premature newborns of gestational age (GA) 25/0-27/6 weeks,

You may not qualify if:

• Missing written parental consent
• Damages to the nasal mucosa
• Maxillofacial defects
• Major congenital anomalies (including chromosomal aberrations, cyanotic congenital heart defects, syndromes likely affecting long-term outcome, and major congenital malformations requiring surgical correction during newborn period)
• Infants who died before 48 hours, infants in whom the clinical decision to withhold intensive care was made, infants who were not considered viable
• Infants with edematous hemolytic disease of newborns, non-immune fetal dropsy,
• Multifetal Gestations
• Participation in another study with ongoing use of an unlicensed investigational product from 28 days before study enrollment until the end of the study

Sponsors & Collaborators

• Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare: lead

Study Sites (1)

Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare

Moscow, 117997, Russia

Location

Related Publications (3)

• Ophelders DR, Wolfs TG, Jellema RK, Zwanenburg A, Andriessen P, Delhaas T, Ludwig AK, Radtke S, Peters V, Janssen L, Giebel B, Kramer BW. Mesenchymal Stromal Cell-Derived Extracellular Vesicles Protect the Fetal Brain After Hypoxia-Ischemia. Stem Cells Transl Med. 2016 Jun;5(6):754-63. doi: 10.5966/sctm.2015-0197. Epub 2016 May 9.

  PMID: 27160705 BACKGROUND

• Drommelschmidt K, Serdar M, Bendix I, Herz J, Bertling F, Prager S, Keller M, Ludwig AK, Duhan V, Radtke S, de Miroschedji K, Horn PA, van de Looij Y, Giebel B, Felderhoff-Muser U. Mesenchymal stem cell-derived extracellular vesicles ameliorate inflammation-induced preterm brain injury. Brain Behav Immun. 2017 Feb;60:220-232. doi: 10.1016/j.bbi.2016.11.011. Epub 2016 Nov 12.

  PMID: 27847282 BACKGROUND

• Gamage TKJB, Fraser M. The Role of Extracellular Vesicles in the Developing Brain: Current Perspective and Promising Source of Biomarkers and Therapy for Perinatal Brain Injury. Front Neurosci. 2021 Sep 24;15:744840. doi: 10.3389/fnins.2021.744840. eCollection 2021.

  PMID: 34630028 RESULT

Related Links

• The Role of Extracellular Vesicles in the Developing Brain: Current Perspective and Promising Source of Biomarkers and Therapy for Perinatal Brain Injury
• The Role of Extracellular Vesicles in the Developing Brain: Current Perspective and Promising Source of Biomarkers and Therapy for Perinatal Brain Injury
• Mesenchymal Stromal Cell-Derived Extracellular Vesicles Protect the Fetal Brain After Hypoxia-Ischemia
• Mesenchymal stem cell-derived extracellular vesicles ameliorate inflammation-induced preterm brain injury

MeSH Terms

Conditions

Premature Birth; Hypoxia-Ischemia, Brain; Neurodevelopmental Disorders

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders

Study Officials

• Oleg Ionov, PhD, MD

  NATIONAL MEDICAL RESEARCH CENTER FOR OBSTETRICS, GYNECOLOGYAND PERINATOLOGY NAMED AFTER ACADEMICIAN V.I.KULAKOV

  PRINCIPAL INVESTIGATOR

• Ekaterina Balashova, PhD, MD

  NATIONAL MEDICAL RESEARCH CENTER FOR OBSTETRICS, GYNECOLOGYAND PERINATOLOGY NAMED AFTER ACADEMICIAN V.I.KULAKOV

  PRINCIPAL INVESTIGATOR

• Denis Silachev, PhD, MD

  NATIONAL MEDICAL RESEARCH CENTER FOR OBSTETRICS, GYNECOLOGYAND PERINATOLOGY NAMED AFTER ACADEMICIAN V.I.KULAKOV

  PRINCIPAL INVESTIGATOR

• Anna Kirtbaya, PhD, MD

  NATIONAL MEDICAL RESEARCH CENTER FOR OBSTETRICS, GYNECOLOGYAND PERINATOLOGY NAMED AFTER ACADEMICIAN V.I.KULAKOV

  PRINCIPAL INVESTIGATOR

• Victor Zubkov, PhD, MD

  NATIONAL MEDICAL RESEARCH CENTER FOR OBSTETRICS, GYNECOLOGYAND PERINATOLOGY NAMED AFTER ACADEMICIAN V.I.KULAKOV

  PRINCIPAL INVESTIGATOR

• Dmitriy Degtyarev, PhD, MD

  NATIONAL MEDICAL RESEARCH CENTER FOR OBSTETRICS, GYNECOLOGYAND PERINATOLOGY NAMED AFTER ACADEMICIAN V.I.KULAKOV

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Oleg Ionov, PhD, MD

CONTACT

+74954382277; dr.ionov@hotmail.com

Diiana Sharafutdinova

CONTACT

+79859865567; dikarush@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Participants (ELBW infants GA 25/0-27/6 week) are randomized to one of two groups in parallel for the duration of the study. The first group (exosome treatment group) will receive intranasal administration of exosomes and the second (control group) will not receive exosomes. Patients in both groups will receive standard basic therapy

Study Record Dates

• First Submitted: July 4, 2022
• First Posted: August 5, 2022
• Study Start: October 5, 2022
• Primary Completion (Estimated): May 22, 2026
• Study Completion (Estimated): December 28, 2026
• Last Updated: September 28, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)