Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pilot of a Prebiotic and Probiotic Trial in Young Infants With Severe Acute Malnutrition

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: NCT03666572
Recruitment Status : Recruiting
First Posted : September 12, 2018
Last Update Posted : February 28, 2019
Sponsor:
Information provided by (Responsible Party):
International Centre for Diarrhoeal Disease Research, Bangladesh

Brief Summary:

Malnutrition is an ever-present problem worldwide. It is estimated that over 18 million children under the age of 5 are affected by the most extreme form of under nutrition, severe acute malnutrition (SAM). Inspite of having standardized management protocols, in many hospitals inpatient mortality reaches up to 30%. Infectious morbidity is common among survivors. Diarrhea, severe intestinal inflammation, low concentrations of fecal short chain fatty acids (SCFAs), and severe systemic inflammation are significantly associated with mortality in SAM. Investigators of this study have earlier shown that the gut microbiota in children with SAM is immature and is causally related with SAM.

Human milk contains between 10 and 20 g/liter of oligosaccharides (human milk oligosaccharides-HMOs) which is the third most abundant solid component after lactose and lipids. HMOs are resistant to gastrointestinal digestion in host infants, and thus the greater part of HMOs reached the colon and may act as prebiotics to shape a healthy gut ecosystem by stimulating the growth of useful microorganisms by acting as receptor analogues to inhibit the binding of various pathogens and toxins to epithelial cells. Probiotics are live organisms beneficial for healthy life. The human digestive tract possesses a diverse microbial community throughout its extent, which support their hosts generally for healthy living. Bifidobacterium spp. is dominant microbiota in infants who are exclusively breastfed and these infants are less likely to suffer from diarrhea. According to recent studies among the most common probiotics genera Lactobacillus and Bifidobacterium, the latter is more abundant in the gut. To carry out their functional activities, Bifidobacteria must be able to survive the gastrointestinal tract transit and persist, at least transiently, in the host. The population of Bifidobacteria in the gut community drastically decreases after weaning. Certain Bifidobacteria possess the metabolic capabilities to break down the HMOs. Consequently it is observed that HMOs support the growth of select Bifidobacteria in the gut of the infant.

Research done at icddr,b and Washington University indicates that gut microbes are related to undernutrition and that children with SAM have gut dysbiosis that mediates some of the pathology of their condition. The standard of care in these children should be reinforced by an intervention that corrects the gut dysbiosis, improves weight gain during nutritional rehabilitation and reduces infectious morbidity. Investigators do not have any published data on the microbiome response to probiotic supplementation (with and without prebiotics) in malnourished infants or preserving the microbiome with probiotics in non-malnourished children.

A short-term pilot study should be conducted to evaluate the microbiome response to probiotic supplementation (with and without prebiotics) in malnourished population to justify a larger study of clinical outcomes. Additionally, non-malnourished infants who are hospitalized for infectious conditions face challenges related to gut dysbiosis caused by antibiotic usage. Here the investigators will evaluate the ability of a probiotic intervention to rescue the microbiome of primarily breastfed non-malnourished infants.

Intervention: Bifidobacterium longum subspecies infantis (EVC001) with and without prebiotic supplementation for 28 days.

Objectives: To evaluate the microbiome response to probiotic supplementation (with and without prebiotics) in infants under 6 months with severe acute malnutrition and to compare the microbiome response with healthy infants with a probiotic.

Methods: Single-blind RCT, stratified randomization will be based on infant age at time of transfer to Nutritional Rehabilitation Unit (NRU).

3 treatment arms for infants with SAM

  1. Placebo (Lactose)
  2. Bifidobacterium infantis alone (Bif)
  3. Bifidobacterium infantis + prebiotic Lacto-N-neotetraose [LNnT] (Bif+prebiotic) Age at enrollment

    1. 2-3.9 months of age
    2. 4-5.9 months of age 1 open-label treatment arm for 18 non-malnourished primarily breastfed infants: Bifidobacterium infantis alone (Bif)

Population:

  1. Group 1 (SAM): Infants between 2 and <6 months old with SAM as defined by weight-for-length Z score < -3, either sex, caregiver willing to provide consent for enrolment of the infant, caregiver willing to stay in the NRU for about 15 days, residence within 15 km from icddr,b
  2. Group 2 (non-malnourished): Non-malnourished infants (WLZ ≥ -1) <6 months old who are hospitalized for treatment with antibiotics for infection, infants receiving at least 50% of nutritional intake from breast milk at the time of hospitalization, either sex, residence within 15 km from icddr,b

Primary Outcome measures/variables:

Bifidobacterium infantis colonization measured by qPCR during and after supplementation (with and without prebiotics)


Condition or disease Intervention/treatment Phase
Severe Acute Malnutrition Other: Bifidobacterium infantis Other: Bifidobacterium infantis with prebiotic Lacto-N-neotetraose [LNnT] Other: Placebo (Lactose) Phase 2

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

3 treatment arms for infants with SAM

  • Placebo (Lactose)
  • B. infantis alone (Bif)
  • B. infantis + prebiotic Lacto-N-neotetraose [LNnT] (Bif+prebiotic)

Age at enrollment

  • 2-3.9 months of age
  • 4-5.9 months of age

    1. open-label treatment arm for 18 non-malnourished primarily breastfed infants - B. infantis alone (Bif)
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Pilot of a Prebiotic and Probiotic Trial in Young Infants With Severe Acute Malnutrition
Actual Study Start Date : October 15, 2018
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 15, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malnutrition

Arm Intervention/treatment
Active Comparator: B. infantis alone (Bif) in SAM infants
B. infantis alone (Bif) in Severe Acute Malnourished infants
Other: Bifidobacterium infantis with prebiotic Lacto-N-neotetraose [LNnT]
Bifidobacterium infantis with prebiotic Lacto-N-neotetraose [LNnT]

Other: Placebo (Lactose)
Placebo (Lactose)

Active Comparator: B. infantis + prebiotic Lacto-N-neotetraose [LNnT]
B. infantis + prebiotic Lacto-N-neotetraose [LNnT] (Bif+prebiotic) in Severe Acute Malnourished infants
Other: Bifidobacterium infantis
Bifidobacterium longum subsp. infantis (EVC001)

Placebo Comparator: Placebo (Lactose)
Placebo (Lactose) in Severe Acute Malnourished infants
Other: Bifidobacterium infantis
Bifidobacterium longum subsp. infantis (EVC001)

Other: Bifidobacterium infantis with prebiotic Lacto-N-neotetraose [LNnT]
Bifidobacterium infantis with prebiotic Lacto-N-neotetraose [LNnT]

Active Comparator: B. infantis alone (Bif) in Not SAM Infants
B. infantis alone (Bif) in not Severe Acute Malnourished infants
Other: Bifidobacterium infantis
Bifidobacterium longum subsp. infantis (EVC001)

Other: Bifidobacterium infantis with prebiotic Lacto-N-neotetraose [LNnT]
Bifidobacterium infantis with prebiotic Lacto-N-neotetraose [LNnT]

Other: Placebo (Lactose)
Placebo (Lactose)




Primary Outcome Measures :
  1. Number of colonization of Bifidobacterium infantis in the intestine of the study participants as measured by qPCR during and after 28 days of supplementation (with and without prebiotics) [ Time Frame: 28 days ]
    Number of colonization of Bifidobacterium infantis in the intestine of the study participants as measured by qPCR during and after 28 days of supplementation (with and without prebiotics)


Secondary Outcome Measures :
  1. Baseline composition of gut microbiota of the study participants as estimated by metagenomic analysis [ Time Frame: 28 days ]
    Baseline composition of gut microbiota of the study participants as estimated by metagenomic analysis

  2. Bifidobacterium colonization (relative abundance) estimated by metagenomic analysis during/after supplementation of 28 days [ Time Frame: 28 days ]
    Bifidobacterium colonization (relative abundance) estimated by metagenomic analysis during/after supplementation of 28 days

  3. Colonization of naturally occurring Bifidobacterium infantis strains identified by qPCR [ Time Frame: 28 days ]
    Colonization of naturally occurring Bifidobacterium infantis strains identified by qPCR

  4. Baseline stool pH [ Time Frame: At screening ]
    Baseline stool pH

  5. Change from baseline in stool pH during supplementation for 28 days [ Time Frame: 28 days ]
    Change from baseline in stool pH during supplementation for 28 days

  6. Composition of breast milk microbiota [ Time Frame: 28 days ]
    Composition of breast milk microbiota

  7. Breast milk Human Milk oligosaccharide contents [ Time Frame: 28 days ]
    Breast milk Human Milk oligosaccharide contents

  8. Rate of body weight gain (g/kg per day) by the study participants (Secondary clinical outcome for Severe Acute Malnourished infants) [ Time Frame: 8 weeks ]
    Rate of body weight gain (g/kg per day) by the study participants

  9. Morbidity during Nutrition Rehabilitation Unit stay and post-discharge including number of (Secondary clinical outcome for Severe Acute Malnourished infants) [ Time Frame: 8 weeks ]
    Morbidity during Nutrition Rehabilitation Unit stay and post-discharge including number of episodes requiring re-hospitalization

  10. Recovery from Severe Acute Malnourished state by the infants as measured by absence (Secondary clinical outcome for Severe Acute Malnourished infants) [ Time Frame: 2 weeks (approximated) ]
    Recovery from Severe Acute Malnourished state by the infants as measured by absence of bi-pedal edema and or achievement of Weight-for-Length Z-score ≥ -2

  11. Recovery from moderate acute malnutrition (MAM) measured by achievement of Weight-for-Length Z-score ≥ -1 (Secondary clinical outcome for Severe Acute Malnourished infants) [ Time Frame: 8 weeks ]
    Recovery from moderate acute malnutrition (MAM) measured by achievement of Weight-for-Length Z-score ≥ -1

  12. Length-for-age Z score measured by length (Secondary clinical outcome for Severe Acute Malnourished infants) [ Time Frame: 8 weeks ]
    Length-for-age Z score measured by length

  13. Fecal Myeloperoxidase levels (Secondary clinical outcome for Severe Acute Malnourished infants) [ Time Frame: 28 days ]
    Fecal Myeloperoxidase levels.

  14. Duration of hospital stay (Secondary clinical outcome for Not Severe Acute Malnourished infants) [ Time Frame: Through study completion, an average of 2 weeks ]
    Duration of hospital stay

  15. Re-hospitalization rates (Secondary clinical outcome for Not Severe Acute Malnourished infants) [ Time Frame: 6 weeks ]
    Re-hospitalization rates

  16. Fecal Myeloperoxidase levels. (Secondary clinical outcome for Not Severe Acute Malnourished infants) [ Time Frame: 28 days ]
    Fecal Myeloperoxidase levels.



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.


Layout table for eligibility information
Ages Eligible for Study:   2 Months to 6 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Group 1 (SAM):

  • Infants between 2 and <6 months old with SAM as defined by weight-for-length <-3 Z-score
  • either sex
  • caregiver willing to provide consent for enrolment of the infant
  • caregiver willing to stay in the Nutritional Rehabilitation Unit for about 15 days
  • residence within 15 km from icddr,b

Group 2 (non-malnourished):

  • Non-malnourished infants (WLZ ≥ -1) <6 months old who are hospitalized for treatment with antibiotics for infection
  • infant receiving at least 50% of nutritional intake from breast milk at the time of hospitalization
  • either sex
  • residence within 15 km from icddr,b

Exclusion Criteria:

  • Septic shock or very severe pneumonia requiring assisted ventilation
  • acute kidney injury on admission
  • congenital defects interfering with feeding such as cleft palate
  • chromosomal anomalies
  • jaundice
  • tuberculosis
  • presence of bilateral pedal edema ongoing maternal antibiotic usage for breastfeeding infants

Group 1 (SAM) additional exclusion criteria:

Infants receiving ≥75% of nutrition from breast milk

Group 2 (non-malnourished) additional exclusion criteria:

Infants receiving <50% of nutrition from breast milk


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): NCT03666572


Contacts
Layout table for location contacts
Contact: M.A Salam Khan +880-2-9827001-10 ext 3206 salamk@icddrb.org

Locations
Layout table for location information
Bangladesh
Dhaka Hospital, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) Recruiting
Dhaka, Bangladesh
Contact: Md Munirul Islam, MBBS, PhD         
Principal Investigator: Tahmeed Ahmed, MBBS, PhD         
Sub-Investigator: Sharika Nuzhat, MBBS, DCH         
Sub-Investigator: Md. Shafiqul Alam Sarker, MD, PhD         
Sub-Investigator: Mustafa Mahfuz, MBBS, MPH         
Sub-Investigator: Md Munirul Islam, MBBS, PhD         
Sponsors and Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh
Investigators
Layout table for investigator information
Principal Investigator: Tahmeed Ahmed, MBBS, PhD International Centre for Diarrhoeal Disease Research, Bangladesh

Publications:

Layout table for additonal information
Responsible Party: International Centre for Diarrhoeal Disease Research, Bangladesh
ClinicalTrials.gov Identifier: NCT03666572     History of Changes
Other Study ID Numbers: PR-17112
First Posted: September 12, 2018    Key Record Dates
Last Update Posted: February 28, 2019
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by International Centre for Diarrhoeal Disease Research, Bangladesh:
Severe Acute Malnutrition
Young Infants under 6 months age
Microbiome
Prebiotics
Probiotics

Additional relevant MeSH terms:
Layout table for MeSH terms
Malnutrition
Severe Acute Malnutrition
Nutrition Disorders