Premature BirthEarly Phase 1NCT04004091

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

A Early Phase 1 study testing Spermine in people with Premature Birth and NEC, run by dr. Riana Pauline Tamba, SpB(K)BA at 1 site in Indonesia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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. Read more about this study

Who is it for?: Ages 24 to 28 daysHealthy volunteers can take part
Conditions the study is for: Premature Birth, NEC
What is being tested?: Spermine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 42 participants
Where: 1 siteIndonesia
Study dates: 1 Mar 2019to 30 Sep 2019
Phase: Early Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 24 to 28 days
All sexes
Healthy volunteers accepted
Child

Who may be able to join

Intestinal tissue of fetal rabbit that is prematurely alive

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Indonesia1 site

Dr. Cipto Mangunkusumo National Hospital
Jakarta Pusat, Jakarta Special Capital Region, 10340

Other trials in Indonesia

About this study

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

Read the 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.

Conditions: Premature Birth, NEC
Being tested: Spermine
Keywords: Premature Birth, Spermine, Necrotizing Enterocolitis, Tight Junction
Medical subject headings: Premature Birth, Enterocolitis, Necrotizing

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT04004091
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: 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.

What is being measured

The primary outcome is the main question the study is designed to answer.

Occludin
Measurement of occludin (ng/mg protein) from intestinal tissue sample is assessed using Rabbit Occludin ELISA Kit
Measured: 2 weeks
β-catenin
Measurement of β-catenin (pg/mg protein) from intestinal tissue sample is assessed using Rabbit β-Catenin ELISA Kit
Measured: 2 weeks
β-actin
Measurement of β-actin (ng/mg protein) from intestinal tissue sample is assessed using β-Actin ELISA Kit
Measured: 2 weeks

Secondary outcomes (1)

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.
Measured: 2 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Mar 201930 Sep 2019

First posted1 Jul 2019
Study start1 Mar 2019
Primary completion30 Sep 2019
Study completion30 Sep 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (7)Papers the sponsor has linked to this study.
Other trials for Premature BirthStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Early Phase 1
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 42 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04004091
Sponsor's protocol ID: tight junction, spermine
Status last verified: Mar 2020
First submitted: 26 Jun 2019
Last updated: 17 Mar 2020
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 26997172
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.
PubMed 15308338
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.
PubMed 15097442
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.
PubMed 11435503
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.
PubMed 9783060
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.
PubMed 8818200
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.
PubMed 8529008

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study of the Influence of Intraperitoneal Insufflation of CO2 by Laparoscopy on the Short-term Evolution of Premature Infants With Ulcerative Necrotizing Enterocolitis
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Multidimensional Dynamic Early Warning System for Neonatal Necrotizing Enterocolitis: A Multicenter Clinical Study
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Optimization of Saturation Targets And Resuscitation Trial (OptiSTART)
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All Premature Birth trials

Study at a glance

From the registry record, last updated by the sponsor on 17 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Prenatal Administration of Oral Spermine Promotes Maturation of Premature Fetal Gut Epithelial Tight Junction: Experimental Study on Oryctolagus Cuniculus
ClinicalTrials.gov ID: NCT04004091
Acronym / sponsor ID: tight junction, spermine
Conditions: Premature Birth, NEC
Keywords: Premature Birth, Spermine, Necrotizing Enterocolitis, Tight Junction
Phase: Early Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 42 participants (actual)
Lead sponsor: dr. Riana Pauline Tamba, SpB(K)BAUniversity, hospital or other
Study start: 1 Mar 2019 (actual)
Primary completion: 30 Sep 2019 (actual)
Study completion: 30 Sep 2019 (actual)
First posted: 1 Jul 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 6

Arm	Type	Receives
24-Day Spermine Group	Experimental	Biological: SpermineSubjects 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.
26-Day Spermine Group	Experimental	Biological: SpermineSubjects 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.
28-Day Spermine Group	Experimental	Biological: SpermineSubjects 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.
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.

Who may qualify

Ages: 24 to 28 days
Sex: All
Healthy volunteers: Accepted
Age groups: Child

Key inclusion criteria (1 listed)

Intestinal tissue of fetal rabbit that is prematurely alive

Key exclusion criteria (2 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SpermineSpermine is a polyamine. It is an organic molecule that is involved in cellular metabolism and development.	Biological	24-Day Spermine Group, 26-Day Spermine Group, 28-Day Spermine Group

Primary outcome

Occludin
Time frame: 2 weeks
Measurement of occludin (ng/mg protein) from intestinal tissue sample is assessed using Rabbit Occludin ELISA Kit
β-catenin
Time frame: 2 weeks
Measurement of β-catenin (pg/mg protein) from intestinal tissue sample is assessed using Rabbit β-Catenin ELISA Kit
β-actin
Time frame: 2 weeks
Measurement of β-actin (ng/mg protein) from intestinal tissue sample is assessed using β-Actin ELISA Kit

1 secondary outcome

Histologic Findings
Time frame: 2 weeks

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2020.
Background: PubMed 26997172van 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.
Background: PubMed 15308338Peulen 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.
Background: PubMed 15097442Peulen 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.
Background: PubMed 11435503Greco 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.
Background: PubMed 9783060Peulen 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.
Background: PubMed 8818200Wery 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.
Background: PubMed 8529008Harada 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.
Individual participant dataSharing planned: No

Related trials for Premature Birth

Not yet recruiting
nCPAP-NAVA-Backup Versus Standard nCPAP for Severe Apnea in Preterm Infants ≤28 Weeks
Apnea of Prematurity
Recruiting
Study of the Influence of Intraperitoneal Insufflation of CO2 by Laparoscopy on the Short-term Evolution of Premature Infants With Ulcerative Necrotizing Enterocolitis
Preterm Birth, Enterocolitis, Necrotizing
RecruitingObservational study
Multidimensional Dynamic Early Warning System for Neonatal Necrotizing Enterocolitis: A Multicenter Clinical Study
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Recruiting
Optimization of Saturation Targets And Resuscitation Trial (OptiSTART)
Premature Infants, Bronchopulmonary Dysplasia
RecruitingObservational study
Growing Little PEAPODS Study
Premature Birth, Premature Infant

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Spermine in people with Premature Birth and NEC, run by dr. Riana Pauline Tamba, SpB(K)BA at 1 site in Indonesia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Indonesia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Occludin (time frame: 2 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04004091, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2020.