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

Sponsor
Fundacion Clinic per a la Recerca Biomédica (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT05945017
Collaborator
Hospital Clinic of Barcelona (Other)
233
1
2
168
1.4

Study Details

Study Description

Brief Summary

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

  1. 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.

Condition or Disease Intervention/Treatment Phase
  • Dietary Supplement: Infloran® -Berne, Switzerland- (Bifidobacterium bifidum NCDO 2203 and Lactobacillus acidophilus NCDO 1748
N/A

Study Design

Study Type:
Interventional
Actual Enrollment :
233 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
Sequential study with consecutive recruitment with a washout period of 12 months between groupsSequential study with consecutive recruitment with a washout period of 12 months between groups
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Probiotics and the Neurodevelopment in the Premature Infant <32 Weeks Gestational Age and <1500g
Actual Study Start Date :
Jan 1, 2014
Actual Primary Completion Date :
Dec 31, 2019
Anticipated Study Completion Date :
Dec 31, 2027

Arms and Interventions

Arm Intervention/Treatment
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

No Intervention: Control

Untreated control group

Outcome Measures

Primary Outcome Measures

  1. Neurodevelopment at 24 months corrected age [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.

  2. Neurodevelopment at 24 months corrected age [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.

  3. Neurodevelopment at 24 months corrected age [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.

  4. Neurodevelopment at 24 months corrected age [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

  5. Neurodevelopment at 6 years of age [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. Neurodevelopment at 6 years of age [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"

  7. Neurodevelopment at 6 years of age [6 years]

    Behavior Rating Inventory of Executive Function, Second Edition (BRIEF2). Parent/teacher self reporting form.

  8. Neuroplasticity biomarkers and intestinal permeability [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

Secondary Outcome Measures

  1. Incidence of necrotising enterocolitis [40 weeks]

    cases fulfilling the stage II or above of the modified Bell's Criteria

  2. Mortality [40 weeks]

    Proportion of dead participants before discharge

  3. Incidence of late onset sepsis [40 weeks]

    positive blood culture beyond 72 hours of life

  4. Incidence of Intraventricular haemorrhage [40 weeks]

    Grade I-IV

  5. Intensive care length of stay [40 weeks]

    Days of intensive care

Eligibility Criteria

Criteria

Ages Eligible for Study:
N/A to 32 Weeks
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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)

Contacts and Locations

Locations

Site City State Country Postal Code
1 Neonataology Service, BCNatal Hospital Clinic Seu Maternitat Barcelona Spain 08028

Sponsors and Collaborators

  • Fundacion Clinic per a la Recerca Biomédica
  • 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

Study Documents (Full-Text)

More Information

Publications

Responsible Party:
Fundacion Clinic per a la Recerca Biomédica
ClinicalTrials.gov Identifier:
NCT05945017
Other Study ID Numbers:
  • HCB/2021/0454
First Posted:
Jul 14, 2023
Last Update Posted:
Jul 14, 2023
Last Verified:
Jul 1, 2023
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Fundacion Clinic per a la Recerca Biomédica
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 14, 2023