Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT02552706
Other study ID # LL2014006
Secondary ID
Status Recruiting
Phase N/A
First received September 12, 2015
Last updated March 26, 2016
Start date September 2014
Est. completion date September 2017

Study information

Verified date September 2015
Source Shenzhen Bao'an Maternal and Child Health Hospital
Contact Yuefeng Li, M.D.
Phone 86+13751029103
Email liyuefeng111@sina.com
Is FDA regulated No
Health authority China: Shenzhen Science and Technology Innovation Committee
Study type Interventional

Clinical Trial Summary

The purpose of this study is to investigate the efficacy and its mechanisms of oral mixture probiotics in preventing necrotizing enterocolitis among the preterm very low birth weight infants.


Description:

Necrotizing enterocolitis (NEC) remains the most catastrophic gastrointestinal emergencies in preterm very low birth weight (VLBW) infants.Although study showed it is a multifactorial disease, its pathogenesis is still not yet unclear currently. Prematurity and formula feeding is considered as the main risk factors.Gut microbiota disturbance and immature immune system is associated with NEC. A lot of studies had showed that oral probiotics can alter gut microbiota flora colonization and reduce the incidence of NEC,but the exact mechanism remains unclear.The aim of this study is to elucidate the clinical efficacy and possible molecular mechanism of oral mixture probiotics in preventing NEC among preterm VLBW infants.

Patient Registry procedures: First,randomized numbers was generated by the computer and sent to the principal investigator(PI) at each center when an infant was eligible for enrollment.Second, patient will be assigned randomly to experimental group or control group by PI.Finally,the PI at each center will be responsible for the accuracy,completeness or representativeness of medical records, registry forms,data collection.

Sample size determination: The incidence of death and NEC was around 20% recently.To reduce the incidence of NEC and death to 10% at discharge would require a 50% improvement.At 80% power at P = 0.05 (two-sided),the loss rate of 0.2, this would require 135 subjects per arm.

Statistical analysis:The two groups were compared by a Χ2-test for categorical variables,Mann-Whitney U Test were used when reporting medians.A P value of <0.05 was considered statistically significant.


Recruitment information / eligibility

Status Recruiting
Enrollment 270
Est. completion date September 2017
Est. primary completion date January 2017
Accepts healthy volunteers No
Gender Both
Age group N/A to 3 Days
Eligibility Inclusion Criteria:

- Preterm infants ? 34 weeks gestational age and birth weight below 1500 gm and who survive to NICU are eligible for the trial.

Exclusion Criteria:

- severe asphyxia (stage III),

- fetal chromosomal anomalies,

- cyanotic congenital heart disease,

- congenital intestinal atresia, gastroschisis, omphalocele, active upper gastric intestinal bleeding,

- lacking/refused of parental consent,

- those who are fasted for >3 weeks during the study period.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention


Intervention

Dietary Supplement:
probiotics
Administration of mixture probiotics 500mg by mouth, one time or divided into 2-4 times depends on the feeding volume until to 36 weeks post menstrual age.
glucose solution
Administration of 1 mL of a 5% glucose solution by mouth, one time or divided into 2-4 times depends on the feeding volume until to 36 weeks post menstrual age.

Locations

Country Name City State
China Longhua People's Hospital of Shenzhen Shenzhen Guangdong
China Shenzhen Bao'an Maternal and Child Health Hospital Shenzhen Guangdong
China Shenzhen People's Hospital Shenzhen Guangdong
China Shenzhen Sixth People's Hospital Shenzhen Guangdong

Sponsors (5)

Lead Sponsor Collaborator
Shenzhen Bao'an Maternal and Child Health Hospital China Medical University Hospital, Longhua Hospital Of Baoan District, Shenzhen, Shenzhen People's Hospital, Shenzhen Sixth People's Hospital

Country where clinical trial is conducted

China, 

References & Publications (17)

Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R, Adler A, Vera Garcia C, Rohde S, Say L, Lawn JE. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a — View Citation

Deshpande G, Rao S, Patole S, Bulsara M. Updated meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates. Pediatrics. 2010 May;125(5):921-30. doi: 10.1542/peds.2009-1301. Epub 2010 Apr 19. — View Citation

Di Gioia D, Aloisio I, Mazzola G, Biavati B. Bifidobacteria: their impact on gut microbiota composition and their applications as probiotics in infants. Appl Microbiol Biotechnol. 2014 Jan;98(2):563-77. doi: 10.1007/s00253-013-5405-9. Epub 2013 Nov 28. Re — View Citation

Ganguli K, Meng D, Rautava S, Lu L, Walker WA, Nanthakumar N. Probiotics prevent necrotizing enterocolitis by modulating enterocyte genes that regulate innate immune-mediated inflammation. Am J Physiol Gastrointest Liver Physiol. 2013 Jan 15;304(2):G132-4 — View Citation

Genzel-Boroviczény O, MacWilliams S, Von Poblotzki M, Zoppelli L. Mortality and major morbidity in premature infants less than 31 weeks gestational age in the decade after introduction of surfactant. Acta Obstet Gynecol Scand. 2006;85(1):68-73. — View Citation

Hackam DJ, Afrazi A, Good M, Sodhi CP. Innate immune signaling in the pathogenesis of necrotizing enterocolitis. Clin Dev Immunol. 2013;2013:475415. doi: 10.1155/2013/475415. Epub 2013 May 23. Review. — View Citation

Hall NJ, Eaton S, Pierro A. Royal Australasia of Surgeons Guest Lecture. Necrotizing enterocolitis: prevention, treatment, and outcome. J Pediatr Surg. 2013 Dec;48(12):2359-67. doi: 10.1016/j.jpedsurg.2013.08.006. Review. — View Citation

Huda S, Chaudhery S, Ibrahim H, Pramanik A. Neonatal necrotizing enterocolitis: Clinical challenges, pathophysiology and management. Pathophysiology. 2014 Feb;21(1):3-12. doi: 10.1016/j.pathophys.2013.11.009. Epub 2014 Feb 11. — View Citation

Lin HC, Hsu CH, Chen HL, Chung MY, Hsu JF, Lien RI, Tsao LY, Chen CH, Su BH. Oral probiotics prevent necrotizing enterocolitis in very low birth weight preterm infants: a multicenter, randomized, controlled trial. Pediatrics. 2008 Oct;122(4):693-700. doi: 10.1542/peds.2007-3007. — View Citation

Liu Y, Fatheree NY, Mangalat N, Rhoads JM. Lactobacillus reuteri strains reduce incidence and severity of experimental necrotizing enterocolitis via modulation of TLR4 and NF-?B signaling in the intestine. Am J Physiol Gastrointest Liver Physiol. 2012 Mar — View Citation

Lu P, Sodhi CP, Hackam DJ. Toll-like receptor regulation of intestinal development and inflammation in the pathogenesis of necrotizing enterocolitis. Pathophysiology. 2014 Feb;21(1):81-93. doi: 10.1016/j.pathophys.2013.11.007. Epub 2013 Dec 22. — View Citation

Mshvildadze M, Neu J, Mai V. Intestinal microbiota development in the premature neonate: establishment of a lasting commensal relationship? Nutr Rev. 2008 Nov;66(11):658-63. doi: 10.1111/j.1753-4887.2008.00119.x. Review. — View Citation

Nair V, Soraisham AS. Probiotics and prebiotics: role in prevention of nosocomial sepsis in preterm infants. Int J Pediatr. 2013;2013:874726. doi: 10.1155/2013/874726. Epub 2013 Jan 14. — View Citation

Quigley MA, Henderson G, Anthony MY, McGuire W. Formula milk versus donor breast milk for feeding preterm or low birth weight infants. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD002971. Review. Update in: Cochrane Database Syst Rev. 2014;4:CD002971. — View Citation

Rees CM, Pierro A, Eaton S. Neurodevelopmental outcomes of neonates with medically and surgically treated necrotizing enterocolitis. Arch Dis Child Fetal Neonatal Ed. 2007 May;92(3):F193-8. Epub 2006 Sep 19. Review. — View Citation

Sarowska J, Choroszy-Król I, Regulska-Ilow B, Frej-Madrzak M, Jama-Kmiecik A. The therapeutic effect of probiotic bacteria on gastrointestinal diseases. Adv Clin Exp Med. 2013 Sep-Oct;22(5):759-66. Review. — View Citation

Sharma R, Tepas JJ 3rd, Hudak ML, Mollitt DL, Wludyka PS, Teng RJ, Premachandra BR. Neonatal gut barrier and multiple organ failure: role of endotoxin and proinflammatory cytokines in sepsis and necrotizing enterocolitis. J Pediatr Surg. 2007 Mar;42(3):45 — View Citation

* Note: There are 17 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Other the influence of oral probiotics on gut microbiota and immunomodulatory test fecal microbiota via high throughput sequencing and blood toll like receptor(TLR)2,TLR4,neclear factor kappa B(NF-KB)were detected using flow cytomtry.Inflammatory factors of blood were tested via Cytometric Bead Array(CBA).All above samples were obtained only from Shenzhen Bao'an Maternal and Child Health Hospital.The fecal DNA were first extracted at centre laboratory in aboved hospital and sent them to Beijing Genomics Institute(BGI) for further sequenceing ,if necessary, quantitative polymerase chain reaction(qPCR)of gut dominant bacterias related to late onset sepsis(LOS) will be tested for assessing the effect of oral probiotics on gut microbiota and underlying the mechanism. Flow cytometry analysis of TLR2,TLR4 and NF-KB were made by the senior laboratorian of our department and resposible for the accuracy of experimental result. CBA of inflammatory factors will be made by senting the blood samples to Beijing JIAMAY BIOLAB. at birth, 2 and 4 weeks of life, 36 week correct gestational age. No
Primary the incidence of combined death and necrotizing enterocolitis at 36 weeks correct gestational age No
Secondary the incidence of sepsis,intraventricular hemorrhage(IVH)(grade 3-4),feeding intolerance(FI),bronchopulmonary dysplasia(BPD),parenteral nutrition associated liver disease(PNALD)and retinopathyof prematurity(ROP). participants will be followed for the duration of hospital stay, an expected average of 8 weeks No
See also
  Status Clinical Trial Phase
Recruiting NCT03646955 - Partial Breast Versus no Irradiation for Women With Early Breast Cancer N/A
Completed NCT01569178 - BAMI. The Effect of Intracoronary Reinfusion of Bone Marrow-derived Mononuclear Cells(BM-MNC) on All Cause Mortality in Acute Myocardial Infarction Phase 3
Recruiting NCT01193751 - Apgar-Score in Asphyxiated Infants Under Resuscitation N/A
Active, not recruiting NCT01597453 - NOR-SYS: The Norwegian Stroke in the Young Study N/A
Completed NCT00399503 - Assessment of Noninvasive Methods to Identify Patients at Risk of Serious Arrhythmias After a Heart Attack N/A
Completed NCT05128799 - Effect of the 3 Wishes Program on Bereaved Families' End-of-Life Care Perceptions
Completed NCT00340015 - A Prospective Study of Diet and Cancer in Members of the American Association of Retired Persons
Active, not recruiting NCT01618123 - Association of Endothelial Function and Clinical Outcomes in Subjects Admitted to Chest Pain Unit
Completed NCT01008241 - South Florida Residents Knowledge and Opinions on End-of-Life Issues
Completed NCT00225394 - Long Term Use of Valganciclovir for Prophylaxis of CMV Disease in Kidney and Pancreas Transplant Patients Phase 4
Terminated NCT05518474 - Self-proning and Repositioning in COVID-19 Outpatients at Risk of Complicated Illness N/A
Completed NCT02533128 - Biomarkers, Blood Pressure, BIS: Risk Stratification/Management of Patients at Cardiac Risk in Major Noncardiac Surgery N/A
Recruiting NCT05199025 - Biomarkers in Perioperative Management
Not yet recruiting NCT06371677 - Polish Nationwide Register of Hospitalized Patients in Cardiac Intensive Care Units
Completed NCT04709120 - Analysis of Health Status of Сomorbid Adult COVID-19 Patients Hospitalised in Second Wave of SARS-CoV-2 Infection
Enrolling by invitation NCT05374291 - The RENAL LIFECYCLE Trial: A RCT to Assess the Effect of Dapagliflozin on Renal and Cardiovascular Outcomes in Patients With Severe CKD Phase 3
Recruiting NCT01792739 - Lactobacillus Preparation on the Incidence of Diarrhea Phase 4
Completed NCT00753428 - Community-based Evaluation of a Pilot PMTCT Project in Kafue District
Completed NCT00912600 - Intensive Care Unit (ICU) Admission Decisions in the Elderly : the ICE-CUB Study N/A
Completed NCT00495690 - Impact of Daily Zinc Supplementation to Infants Born With Low Birth Weight on Death and Severe Disease Phase 3