Format

Send to

Choose Destination
BMJ Open. 2019 Mar 1;9(2):e026265. doi: 10.1136/bmjopen-2018-026265.

Human amnion cells for the prevention of bronchopulmonary dysplasia: a protocol for a phase I dose escalation study.

Author information

1
Newborn Research Centre, The Royal Women's Hospital, Melbourne, Victoria, Australia.
2
Department of Obstetrics and Gynaecology, The University of Melbourne, Melbourne, Victoria, Australia.
3
Monash Newborn, Monash Children's Hospital, Melbourne, Victoria, Australia.
4
Department of Paediatrics, Monash University, Melbourne, Victoria, Australia.
5
The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Victoria, Australia.
6
Department of Obstetrics and Gynaecology, Monash University, Melbourne, Victoria, Australia.

Abstract

INTRODUCTION:

Bronchopulmonary dysplasia (BPD), an important sequela of preterm birth, is associated with long-term abnormalities of lung function and adverse neurodevelopmental outcomes. Inflammation, inhibition of secondary septation and vascular maldevelopment play key roles in the pathogenesis of BPD. Human amnion epithelial cells (hAECs), stem-like cells, derived from placental tissues are able to modulate the inflammatory milieu and, in preclinical studies of BPD-like injury, restore lung architecture and function. Allogeneic hAECs may present a new preventative and reparative therapy for BPD.

METHODS AND ANALYSIS:

In this two centre, phase I cell dose escalation study we will evaluate the safety of intravenous hAEC infusions in preterm infants at high risk of severe BPD. Twenty-four infants born at less than 29 weeks' gestation will each receive intravenous hAECs beginning day 14 of life. We will escalate the dose of cells contained in a single intravenous hAEC infusion in increments from 2 million cells/kg to 10 million cells/kg. Further dose escalation will be achieved with repeat infusions given at 5 day intervals to a maximum total dose of 30 million cells/kg (three infusions). Safety is the primary outcome. Infants will be followed-up until 2 years corrected age. Additional outcome measures include a description of infants' cytokine profile following hAEC infusion, respiratory outcomes including BPD and pulmonary hypertension and other neonatal morbidities including neurodevelopmental assessment at 2 years.

ETHICS AND DISSEMINATION:

This study was approved on the June12th, 2018 by the Human Research Ethics Committee of Monash Health and Monash University. Recruitment commenced in August 2018 and is expected to take 18 months. Accordingly, follow-up will be completed mid-2022. The findings of this study will be disseminated via peer-reviewed journals and at conferences.

PROTOCOL VERSION:

5, 21 May 2018.

TRIAL REGISTRATION NUMBER:

ACTRN12618000920291; Pre-results.

KEYWORDS:

bronchopulmonary dysplasia; cell therapy; clinical trials; premature infant; stem cells

PMID:
30826799
DOI:
10.1136/bmjopen-2018-026265
Free full text

Conflict of interest statement

Competing interests: None declared.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center