Probiotics and the Neurodevelopment in the Premature Infant <32 Weeks Gestational Age and <1500g

August 10, 2023 updated by: Fundacion Clinic per a la Recerca Biomédica

Unicentric, quasi-experimental, cohort study to evaluate the effect of combining two probiotics (Bifidobacterium bifidum NCDO 2203 and Lactobacillus acidophilus NCDO 1748) in the neurodevelopment of preterm neonates below 32 weeks' gestation and a birthweight under 1,500 g. This probiotic combination has shown to be safe and beneficial in premature neonates in the prevention of NEC. The investigators hypothesised that this mixture would contribute to better neurodevelopmental outcomes of preterm neonates when assessed at 24 months corrected age. Additionally, neurodevelopment improved would be more relevant at 6 years of age, together with a better pattern of neuronal plasticity biomarkers.

Secondarily, this mixture of probiotics could reduce NEC, LOS, intraventricular haemorrhage and neonatal mortality in accordance with previous studies.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

233

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelona, Spain, 08028
        • Neonataology Service, BCNatal Hospital Clinic Seu Maternitat

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Premature infants under 32 weeks gestational age and less than 1500g birthweight.
  • Born at BCNatal Hospital Clínic between years 2014-2019.

Exclusion Criteria:

  • All neonates presenting with suspected congenital anomalies, inborn errors of metabolism, or genetic defects were excluded.
  • Infants with a suspected syndrome, or who have suffered events beyond the neonatal period, not related to prematurity, that could entail impairment in neurodevelopment (severe cranioencephalic trauma, oncological process, meningitis, or exposure to toxic substances)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control
Untreated control group
Experimental: Bifidobacterium bifidum NCDO 2203 and Lactobacillus acidophilus NCDO 1748
Daily dose of 6x109 UFC Infloran® -Berne, Switzerland- (Bifidobacterium bifidum NCDO 2203 and Lactobacillus acidophilus NCDO 1748) from 7 days of life until reaching a postmenstrual age of 34 weeks or discharge
Dietary supplement: Infloran® -Berne, Switzerland- (Bifidobacterium bifidum NCDO 2203 and Lactobacillus acidophilus NCDO 1748

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neuroplasticity biomarkers and intestinal permeability
Time Frame: 6 years
NeuN, Doublecortin, GFAP, GDNF, Ki67, Nrf2, BDNF, NGF, neurotrophin-1 (NT-1), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), DYRK1A, HIF1α, S100B i GSK3B. IL1B, IL6, IL8, IL10, IL12, TNF- α
6 years
Degree of neurodevelopment at 24 months corrected age
Time Frame: 24 months
Normal neurodevelopment will be considered when no muscle tone changes, no impaired fine or gross motor coordination, Bayley scale score between above 84, no behaviour disorders or visual disability.
24 months
Degree of neurodevelopment at 24 months corrected age
Time Frame: 24 months
Mild impairment will be considered if any of the following: muscle tone changes, impaired fine or gross motor coordination, Bayley scale score between 71-84, moderate behaviour disorders or mild visual disability.
24 months
Degree of neurodevelopment at 24 months corrected age
Time Frame: 24 months
Moderate impairment will be diagnosed when suffering from any of the following: spastic diplegia, hemiplegia, seizures (non-febrile), Bayley scores between 50-70, severe behaviour disorders, moderate visual disability or mild-moderate hypoacusis.
24 months
Degree of neurodevelopment at 24 months corrected age
Time Frame: 24 months
Severe impairment will be attributed to subjects with any of the following: spastic quadriplegia, choreoathetosis, ataxia, Bayley score <50, blindness or severe hypoacusis
24 months
Degree of neurodevelopment at 6 years of age
Time Frame: 6 years
Wechsler Intelligence Scale for Children - Fifth edition. Ranges from below 69 to above 130. Scores from 90-109 indicate average, above it indicates above average and below, below average performance.
6 years
Degree of neurodevelopment at 6 years of age
Time Frame: 6 years
Child behaviour checklist 6-18 years of age. 113 items about behaviour and social competence scored from 0 "absent" to 2 "occurs often"
6 years
Degree of neurodevelopment at 6 years of age
Time Frame: 6 years
Behavior Rating Inventory of Executive Function, Second Edition (BRIEF2). Parent/teacher self reporting form.
6 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of necrotising enterocolitis
Time Frame: 40 weeks
cases fulfilling the stage II or above of the modified Bell's Criteria
40 weeks
Mortality
Time Frame: 40 weeks
Proportion of dead participants before discharge
40 weeks
Incidence of late onset sepsis
Time Frame: 40 weeks
positive blood culture beyond 72 hours of life
40 weeks
Incidence of Intraventricular haemorrhage
Time Frame: 40 weeks
Grade I-IV
40 weeks
Intensive care length of stay
Time Frame: 40 weeks
Days of intensive care
40 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fundacion Clinic per a la Recerca Biomédica

Collaborators

Hospital Clinic of Barcelona

Investigators

  • Principal Investigator: Benjamin James Baucells, MD, Neonataology Service, BCNatal Hospital Clínic
  • Principal Investigator: Giorgia Sebastiani, Neonatology Service, BCNatal Hospital Clínic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2014

Primary Completion (Actual)

December 31, 2019

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

May 19, 2023

First Submitted That Met QC Criteria

July 11, 2023

First Posted (Actual)

July 14, 2023

Study Record Updates

Last Update Posted (Actual)

August 14, 2023

Last Update Submitted That Met QC Criteria

August 10, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HCB/2021/0454

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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