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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03858816
Recruitment Status : Recruiting
First Posted : March 1, 2019
Last Update Posted : March 6, 2019
Sponsor:
Information provided by (Responsible Party):
Hung-Chih Lin, China Medical University Hospital

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.

Condition or disease Intervention/treatment Phase
Very Low Birth Weight Infants Other: Mixture probiotics Other: Placebo Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 320 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Efficacy of Multiple Strain Probiotics Reduces the Neurobehavioral Disorder in Premature Very Low Birth Weight Infants
Actual Study Start Date : June 14, 2018
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : June 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Other: Mixture probiotics
The mixture probiotics capsule

Placebo Comparator: Placebo
Taking 1 placebo capsule for up to 4 months after birth.
Other: Placebo
The placebo contains the same excipient ingredients but without the live bacteria.




Primary Outcome Measures :
  1. Incidence rate of death or ADHD and ASD [ Time Frame: Two years ]

Secondary Outcome Measures :
  1. Incidence rate of NEC ≧ stage 2, sepsis, severe (grade 3-4) IVH, BPD, liver function and adverse effects or intolerance and neurodevelopment impairment. [ Time Frame: Two years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03858816


Contacts
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Contact: Hung-chih Lin 886-4-22052121 ext 4640 d0373@mail.cmuh.org.tw

Locations
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Taiwan
Department of Pediatrics, Children Hospital, China Medical University Recruiting
Taichung, Taiwan, 404
Contact: Hung-chih Lin    886-4-22052121 ext 4640    d0373@mail.cmuh.org.tw   
Sponsors and Collaborators
China Medical University Hospital
Additional Information:
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Responsible Party: Hung-Chih Lin, Attending physician, China Medical University Hospital
ClinicalTrials.gov Identifier: NCT03858816    
Other Study ID Numbers: CMUH106-REC2-102
First Posted: March 1, 2019    Key Record Dates
Last Update Posted: March 6, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data for all primary and secondary outcome measures will be made available.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Data will be available within 6 months of study completion.
Access Criteria: Data access requests will be reviewed by an external Independent Review Panel. Requestors will be required to sign a Data Access Agreement.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hung-Chih Lin, China Medical University Hospital:
probiotics
neuropsychiatric disorder
very low birth weight infants
attention deficit and hyperactivity disorder (ADHD)
autism spectrum disorder (ASD)
Additional relevant MeSH terms:
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Body Weight
Birth Weight