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

NCT04004091 | Completed Early Phase 1 FDA Drug

• 1 other identifier: tight junction, spermine
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Premature Birth; NEC

Keywords

Premature Birth; Spermine; Necrotizing Enterocolitis; Tight Junction

Outcome Measures

Primary Outcomes (3)

• Occludin

  Measurement of occludin (ng/mg protein) from intestinal tissue sample is assessed using Rabbit Occludin ELISA Kit

  2 weeks

• β-catenin

  Measurement of β-catenin (pg/mg protein) from intestinal tissue sample is assessed using Rabbit β-Catenin ELISA Kit

  2 weeks

• β-actin

  Measurement of β-actin (ng/mg protein) from intestinal tissue sample is assessed using β-Actin ELISA Kit

  2 weeks

Secondary Outcomes (1)

• Histologic Findings

  2 weeks

Study Arms (6)

24-Day Spermine Group

EXPERIMENTAL

Subjects are given prenatal spermine (20 mg per body weight) during 24 days of pregnancy. On day 24 pregnancy is terminated and intestinal tissue sample is taken to be examined.

Biological: Spermine

26-Day Spermine Group

EXPERIMENTAL

Subjects are given prenatal spermine (20 mg per body weight) during 26 days of pregnancy. On day 26 pregnancy is terminated and intestinal tissue sample is taken to be examined.

Biological: Spermine

28-Day Spermine Group

EXPERIMENTAL

Subjects are given prenatal spermine (20 mg per body weight) during 28 days of pregnancy. On day 28 pregnancy is terminated and intestinal tissue sample is taken to be examined.

Biological: Spermine

24-Day Non Spermine Group

NO INTERVENTION

Subjects are not given any intervention. On day 24 pregnancy is terminated and intestinal tissue sample is taken to be examined.

26-Day Non Spermine Group

NO INTERVENTION

Subjects are not given any intervention. On day 26 pregnancy is terminated and intestinal tissue sample is taken to be examined.

28-Day Non Spermine Group

NO INTERVENTION

Subjects are not given any intervention. On day 28 pregnancy is terminated and intestinal tissue sample is taken to be examined.

Interventions

Spermine BIOLOGICAL

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

24-Day Spermine Group; 26-Day Spermine Group; 28-Day Spermine Group

Eligibility Criteria

• Age: 24 Days - 28 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Intestinal tissue of fetal rabbit that is prematurely alive

You may not qualify if:

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

Sponsors & Collaborators

• dr. Riana Pauline Tamba, SpB(K)BA: lead

Study Sites (1)

Dr. Cipto Mangunkusumo National Hospital

Jakarta Pusat, Jakarta Special Capital Region, 10340, Indonesia

Location

Related Publications (7)

• 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.

  PMID: 26997172 BACKGROUND

• 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.

  PMID: 15308338 BACKGROUND

• 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.

  PMID: 15097442 BACKGROUND

• 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.

  PMID: 11435503 BACKGROUND

• 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.

  PMID: 9783060 BACKGROUND

• 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.

  PMID: 8818200 BACKGROUND

• 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.

  PMID: 8529008 BACKGROUND

MeSH Terms

Conditions

Premature Birth; Enterocolitis, Necrotizing

Interventions

Spermine

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Spermidine; Putrescine; Biogenic Polyamines; Biogenic Amines; Amines; Organic Chemicals; Polyamines

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Consultant Pediatric Surgeon

Study Record Dates

• First Submitted: June 26, 2019
• First Posted: July 1, 2019
• Study Start: March 1, 2019
• Primary Completion: September 30, 2019
• Study Completion: September 30, 2019
• Last Updated: March 17, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)