Efficacy of Multiple Strain Probiotics Reduces the Neurobehavioral Disorder in Premature Very Low Birth Weight Infants

NCT ID: NCT03858816

Last Updated: 2022-03-21

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-14
• Study Completion Date: 2021-06-30

Brief Summary

The management protocols, clinical practices, equipment, infrastructure, and key personnel in NICU are unchanged during the study period. The data collected by each center are transmitted to the office of the principal investigator (Dr Lin) at China Medical University Hospital. Primary outcome is death or attention deficit and hyperactivity disorder (ADHD) and ASD.

Detailed Description

Over the years, preterm very low birth weight (PVLBW) infants (<32 weeks gestation) have better survival rates and improved outcomes. Nonetheless, It is of concern that there are increased risk of psychiatric problems reported in PVLBW infants, 11.5% to 31% of them are reported to be at increased risk of attention deficit and hyperactivity disorder (ADHD) and 25 % of them would develop autism spectrum disorder (ASD).

Many VLBWs experience rapid vaginal or Caesarean births that increased relative risk of developing ASD and possibly ADHD when compared to vaginal delivery. Further, PVLBW infants often experience delays in enteral feeding, and many receive little or no mother's own milk, use of antibiotics, invasive procedures and maternal separation can contribute to dysbiosis and dysbiosis in early life may prone to develop ASD and ADHD There is growing body of evidence demonstrates that gut microbiota is involved in communication, and may impact brain development and modulate behavior. Evidences have showed that there were increased intestinal permeability, altered gut microbiota and activity in autism and ADHD. Studies have demonstrated that early postnatal phase of microbial development is a primer for future health. Giving all the evidence, it is reasonable to speculate that probiotics could reduce the ASD and ADHD in preterm VLBW infants.

From Aug 1, 2017 to June 30, 2020, a prospective, double blind, randomized, controlled trial will be conducted in five NICUs at Taiwan. The study protocol will be approved by the institutional review board of each hospital. Preterm infants ≧ 23 weeks and ≦ 32 weeks gestational age and birth weight below 1500 gm and who survive to NICU are eligible for the trial. They will be assigned randomly to either group A: multiple strian probiotics or group B: control group received 1 mL of a 5% glucose solution. Study is continuous until preterm infants grow up to 4 months postnatal age.

The management protocols, clinical practices, equipment, infrastructure, and key personnel in NICU are unchanged during the study period. The data collected by each center are transmitted to the office of the principal investigator (Dr Lin) at China Medical University Hospital. Primary outcome is death or attention deficit and hyperactivity disorder (ADHD) and ASD.

Mortality is defined as death prior to discharge. Secondary outcomes are NEC ≧ stage 2, sepsis, severe (grade 3-4) IVH, BPD, alteration of liver function, and adverse effects or intolerance and neurodevelopment impairment. Objection of the first two years is to enroll cases, ASD and ADHD will be assessed by two independent neurologists at third year of life; no examiner is aware of treatment assigned to any infant.

Conditions

Very Low Birth Weight Infants

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Mixture probiotics

The probiotic contain 1 ×10\^9 CFU/1 capsule of mixture probiotics, taking 1 probiotic capsule for up to 4 months after birth.

Group Type: EXPERIMENTAL

Mixture probiotics

Intervention Type: OTHER

The mixture probiotics capsule

Placebo

Taking 1 placebo capsule for up to 4 months after birth.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

The placebo contains the same excipient ingredients but without the live bacteria.

Interventions

Mixture probiotics

The mixture probiotics capsule

Intervention Type: OTHER

Placebo

The placebo contains the same excipient ingredients but without the live bacteria.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Preterm infants ≧ 23 weeks and ≦ 32 weeks gestational age.
• Birth weight below 1500 gm and who survive to NICU.

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
• Early onset sepsis (before the third day of life)
• Liver failure (aspartate aminotransferase, alanine aminotransferase, glutamyl transferase, direct bilirubin serum values 3-fold higher than reference range)
• Fasted for >3 weeks.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

China Medical University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Hung-Chih Lin

Attending physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Department of Pediatrics, Children Hospital, China Medical University

Taichung, , Taiwan

Countries

Taiwan

Related Links

http://www.cmuh.cmu.edu.tw/

Related Info

Other Identifiers

CMUH106-REC2-102

Identifier Type: -

Identifier Source: org_study_id