Prenatal Administration of Spermine Promotes Maturation of Premature Fetal Gut Epithelial Tight Junction: Experimental Study on Fetal Rabbit

Premature Birth Clinical Trial

Official title:

Prenatal Administration of Oral Spermine Promotes Maturation of Premature Fetal Gut Epithelial Tight Junction: Experimental Study on Oryctolagus Cuniculus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04004091
• Other study ID #: tight junction, spermine
• Status: Completed
• Phase: Early Phase 1
• Start date: March 1, 2019
• Est. completion date: September 30, 2019

Study information

• Verified date: March 2020
• Source: Indonesia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: September 30, 2019
• Est. primary completion date: September 30, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 28 Days

Eligibility

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

Related Conditions & MeSH terms

• NEC
• Premature Birth

Intervention

Biological:
• Spermine
Spermine is a polyamine. It is an organic molecule that is involved in cellular metabolism and development.

Locations

Country	Name	City	State
Indonesia	Dr. Cipto Mangunkusumo National Hospital	Jakarta Pusat	Jakarta

Sponsors (1)

Lead Sponsor	Collaborator
dr. Riana Pauline Tamba, SpB(K)BA

Country where clinical trial is conducted

Indonesia, 

References & Publications (7)

Gréco 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Wéry 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occludin	Measurement of occludin (ng/mg protein) from intestinal tissue sample is assessed using Rabbit Occludin ELISA Kit	2 weeks
Primary	ß-catenin	Measurement of ß-catenin (pg/mg protein) from intestinal tissue sample is assessed using Rabbit ß-Catenin ELISA Kit	2 weeks
Primary	ß-actin	Measurement of ß-actin (ng/mg protein) from intestinal tissue sample is assessed using ß-Actin ELISA Kit	2 weeks
Secondary	Histologic Findings	Identifying the development of epithelial tight junction cells based on the morphologic findings of the villi structure, including Goblet cells' distribution, enterocytes, enteroendocrine cells, and crypts.	2 weeks