Clinical trial NCT04004091: Prenatal Administration of Spermine Promotes Maturation of Premature Fetal Gut Epithelial Tight Junction: Experimental Study on Fetal Rabbit
Official title: Prenatal Administration of Oral Spermine Promotes Maturation of Premature Fetal Gut Epithelial Tight Junction: Experimental Study on Oryctolagus Cuniculus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Premature Birth
NEC
Keywords: Premature Birth
Spermine
Necrotizing Enterocolitis
Tight Junction
Lead sponsor: Indonesia University
Sponsor class: OTHER
First posted: 2019-07-01
Enrollment: 42
Sex: ALL
Minimum age (years): 24
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Infections, particularly on the gastrointestinal tract, has been known to be one of the leading causes of death in preterm infants. This is due to the immaturity of the intestinal epithelial cells. Recent studies have shown that polyamines have a role on the development of cells during embryonal phase. By this experimental study, the investigators would like to evaluate the administration of spermine on the maturation of premature fetal gut epithelial tight junction.

Detailed description: This experimental study is conducted with minimum 24 subjects which divided into 6 groups; 1) 24-days pregnant and is given prenatal spermine, 2) 26-days pregnant and is given prenatal spermine, 3) 28-days pregnant and is given prenatal spermine, 4) 24-days pregnant and is not given prenatal spermine, 5) 26-days pregnant and is not given prenatal spermine, and 6) 28-days pregnant and is not given prenatal spermine. At the end of desired pregnancy period, hysterectomy is done and fetus are born. From each parent subject, three fetal samples are chosen using a random sampling. Intestinal tissues are taken from each fetal sample to be examined. Several data will be collected i.e. occludin, β-catenin, and β-actin, as well as histological morphologies.

Eligibility criteria: Inclusion Criteria:

* Intestinal tissue of fetal rabbit that is prematurely alive

Exclusion Criteria:

* Intestinal tissue of fetal rabbit that is dead before termination
* Intestinal tissue of fetal rabbit, in which the parent died before termination

Primary outcomes:
measure: Occludin
timeFrame: 2 weeks
measure: β-catenin
timeFrame: 2 weeks
measure: β-actin
timeFrame: 2 weeks
Secondary outcomes:
measure: Histologic Findings
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Jakarta Pusat
country: Indonesia
facility: Dr. Cipto Mangunkusumo National Hospital
state: Jakarta
Study officials:
References:
citation: van Wettere WH, Willson NL, Pain SJ, Forder RE. Effect of oral polyamine supplementation pre-weaning on piglet growth and intestinal characteristics. Animal. 2016 Oct;10(10):1655-9. doi: 10.1017/S1751731116000446. Epub 2016 Mar 21.
citation: Peulen O, Gharbi M, Powroznik B, Dandrifosse G. Differential effect of dietary spermine on alkaline phosphatase activity in jejunum and ileum of unweaned rats. Biochimie. 2004 Jul;86(7):487-93. doi: 10.1016/j.biochi.2004.06.002.
citation: Peulen O, Dandrifosse G. Spermine-induced maturation in wistar rat intestine: a cytokine-dependent mechanism. J Pediatr Gastroenterol Nutr. 2004 May;38(5):524-32. doi: 10.1097/00005176-200405000-00012.
citation: Greco S, Niepceron E, Hugueny I, George P, Louisot P, Biol MC. Dietary spermidine and spermine participate in the maturation of galactosyltransferase activity and glycoprotein galactosylation in rat small intestine. J Nutr. 2001 Jul;131(7):1890-7. doi: 10.1093/jn/131.7.1890.
citation: Peulen O, Pirlet C, Klimek M, Goffinet G, Dandrifosse G. Comparison between the natural postnatal maturation and the spermine-induced maturation of the rat intestine. Arch Physiol Biochem. 1998 Feb;106(1):46-55. doi: 10.1076/apab.106.1.46.4392.
citation: Wery I, Deloyer P, Dandrifosse G. Effects of a single dose of orally-administered spermine on the intestinal development of unweaned rats. Arch Physiol Biochem. 1996;104(2):163-72. doi: 10.1076/apab.104.2.163.12886.
citation: Harada E, Hashimoto Y, Syuto B. Orally administered spermine induces precocious intestinal maturation of macromolecular transport and disaccharidase development in suckling rats. Comp Biochem Physiol A Physiol. 1994 Nov;109(3):667-73. doi: 10.1016/0300-9629(94)90208-9.