Clinical trial NCT05554991: Human Milk Oligosaccharide (HMO) Supplementation in Colic Management
Official title: Efficacy and Tolerability of a Composition Comprising of HMO in a Supplement Format on Colic Management: a Double-blind, Randomized, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Colic
Lead sponsor: Société des Produits Nestlé (SPN)
Sponsor class: INDUSTRY
First posted: 2022-09-26
Enrollment: 5
Sex: ALL
Minimum age (years): 2
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blinded, placebo-controlled, parallel-arm, intervention study
Primary purpose: OTHER

Brief summary: Efficacy and tolerability of a composition comprising of HMO in a supplement format on colic management: a double-blind, randomized, placebo-controlled trial

Detailed description: This is a double-blinded, randomized, placebo-controlled trial. The purpose of this trial is to investigate the efficacy and tolerability of a composition comprising of HMO in a supplement format in the management of colicky infants aged 2-12 weeks.

Eligibility criteria: Inclusion criteria:

1. Infants 2 weeks - 12 weeks of age at enrolment
2. Infants diagnosed with colic according to Rome IV criteria: Diagnostic criteria for research purposes (infant must meet all Rome IV criteria):

   1. An infant who is less than 5 months of age (in the current clinical trial, only infants 2 weeks to 8 weeks of age will be enrolled) when the symptoms start and stop
   2. Recurrent and prolonged periods of infant crying, fussing, or irritability reported by caregivers that occur without obvious cause and cannot be prevented or resolved by caregivers
   3. No evidence of infant failure to thrive, fever, or illness
   4. Excessive crying/fussiness for 3 or more hours per day during 3 or more days in the past 7 days as reported by parents to the clinician
   5. Total 24-hour crying plus fussing is 3 hours or more when measured by at least one prospectively kept 24-hour behavior diary. (The Structured Infant Crying and Fussing Diary will be dispensed at the screening visit (V0), completed for two 24-hour periods at H0 (days -3 to -1), and returned at V1 to be used as part of the diagnostic criteria for infantile colic.)
3. Term infants (≥ 37 weeks) generally healthy with normal birth weight (≥2.5kg) and singleton born
4. Predominantly formula fed\* (formula fed ≥ 80% of the time) for at least 7 days before randomization and the choice of formula feeding has been made by the parents before the beginning of the trial.
5. Infants who have been on the same formula for the past 5 days
6. Signed informed consent obtained for infant's and parents'/Legally Acceptable Representative (LAR) participation in the study
7. Parent/LAR of infant agrees not to enroll infant in another interventional clinical research study while participating in this study
8. Parent of the infant/LAR is willing and able to fulfill the requirements of the study protocol
9. Parent of infant can be contacted throughout the study

   * Predominantly formula feeding defined in the study means that the infant's predominant source of nourishment is formula. Specifically, infants are fed with formula for at least 80% of total milk feeds per day.

Exclusion criteria:

1. Presence of any congenital condition and/or previous or current illness/infection and (or) medication use that could interfere with the main study outcomes.
2. Clinical evidence of chronic illness or gastrointestinal disorders, major medical problems (e.g. ill, immunocompromised, major developmental or genetic abnormality).
3. Known cow's milk protein allergy, lactose intolerance, or galactosaemia; including presence of any allergic manifestations.
4. Received any special formula (e.g. lactose-free, hydrolyzed protein) within 5 days before randomization or switched formulas within 5 days before randomization.
5. Received any of the following products/medication within 5 days before randomization:

   * Antibiotics
   * Alginate
   * Prokinetics
   * Proton pump inhibitors
   * Simethicone
   * L. reuteri probiotic
   * Formula containing Human milk Oligosaccharides
6. Other infant(s) \<6months of age living in the same household.
7. Current participation in another interventional clinical trial.

Primary outcomes:
measure: Difference in average infant daily crying and fussing duration
timeFrame: At the end of the intervention period (day 21)
Secondary outcomes:
measure: Modulation of infant gut microbiota (communities of microbes, their taxonomy, strain composition, diversity, ecology, functionalities, and the metabolites produced)
timeFrame: V1 (day 0), V2 (day 7), and V4 (day 21)
measure: Difference in average infant daily crying duration
timeFrame: Change from baseline (V1) to intervention end (V4)
measure: Difference in average infant daily fussing duration
timeFrame: Change from baseline (V1) to intervention end (V4)
measure: Difference in average infant daily crying and fussing duration in the IG
timeFrame: Change from baseline (V1) to intervention end (V4)
measure: Difference in average infant daily crying duration in the Intervention group
timeFrame: Change from baseline (V1) to intervention end (V4)
measure: Difference in average infant daily fussing duration in the Intervention group
timeFrame: Change from baseline (V1) to intervention end (V4)
measure: Infant daily crying and fussing duration assessed longitudinally
timeFrame: Longitudinal changes across specific visits V1 (day 0), V2 (day 7), V3 (day 14) and V4 (day 21)
measure: Infant crying/fussing per 24 hours
timeFrame: At specific visits V1 (day 0), V2 (day 7), V3 (day 14) and V4 (day 21)
measure: Percentage of children achieving a reduction in daily crying and fussing
timeFrame: At specific visits V1 (day 0), V2 (day 7), V3 (day 14) and V4 (day 21)
measure: Incidence of infantile colic
timeFrame: At specific visits V1 (day 0), V2 (day 7), V3 (day 14) and V4 (day 21)
measure: Parental perception of colic severity
timeFrame: At specific visits V1 (day 0), V2 (day 7), V3 (day 14) and V4 (day 21)
measure: Overall GI tolerance and individual GI symptoms
timeFrame: V1 (day 0), V2 (day 7), V3 (day 14) and V4 (day 21)
measure: Overall GI tolerance and individual GI symptoms
timeFrame: Baseline to intervention end (day 21)
measure: Overall GI tolerance and individual GI symptoms
timeFrame: At V1 (day 0), V2 (day 7), V3 (day 14) and V4 (day 21)
measure: Overall GI tolerance and individual GI symptoms
timeFrame: From baseline to intervention end (day 21)
measure: Overall GI tolerance and individual GI symptoms
timeFrame: 1-day retrospective GI diary at V1 (day 0) and prospective 3-Day GI symptom diary diaries at home (H2, H3 and H4) just prior to V2 (day 7), V3 (day 14) and V4 (day 21)
measure: Infant sleep
timeFrame: V1 (day 0), V2 (day 7), V3 (day 14) and V4 (day 21)
measure: Infant Quality of life
timeFrame: V1 (day 0), V2 (day 7), V3 (day 14) and V4 (day 21)
measure: Parental and family quality of life
timeFrame: V1 (day 0), V2 (day 7), V3 (day 14) and V4 (day 21)
measure: Infant fecal gut microbiota
timeFrame: V1 (day 0), V2 (day 7), and V4 (day 21)
measure: Fecal metabolism
timeFrame: V1 (day 0), V2 (day 7), and V4 (day 21)
measure: Fecal markers of inflammation calprotectin
timeFrame: V1 (day 0) and V4 (day 21)
measure: Fecal markers of inflammation lipocalin
timeFrame: V1 (day 0) and V4 (day 21)
measure: Infant anthropometry weight
timeFrame: V1 (day 0), V2 (day 7), V3 (day 14) (optional if V3 is a phone call) and V4 (day 21)
measure: Infant anthropometry length
timeFrame: V1 (day 0), V2 (day 7), V3 (day 14) (optional if V3 is a phone call) and V4 (day 21)
measure: Infant anthropometry head circumference
timeFrame: V1 (day 0), V2 (day 7), V3 (day 14) (optional if V3 is a phone call) and V4 (day 21)
measure: Infant anthropometry weight gain
timeFrame: V1 (day 0), V2 (day 7), V3 (day 14) (optional if V3 is a phone call) and V4 (day 21)
measure: Infant anthropometry length gain
timeFrame: V1 (day 0), V2 (day 7), V3 (day 14) (optional if V3 is a phone call) and V4 (day 21)
measure: Infant illness and infection and medication usage
timeFrame: V1 (day 0) until V4 (day 21)
Other outcomes:
measure: Duration and number of episodes of infant crying type based on a crying-type classification of the audio recording
timeFrame: 24 hours after V1 (day 0), V2 (day 7), V3 (day 14) and for 3 days prior to V4 (day 21)
measure: Proportion of children with a specific crying type based on a crying-type classification of the audio recording
timeFrame: 24 hours after V1 (day 0), V2 (day 7), V3 (day 14) and for 3 days prior to V4 (day 21)
measure: Duration of crying based on a crying-type classification of the audio recording
timeFrame: 24 hours after V1 (day 0), V2 (day 7), V3 (day 14) and for 3 days prior to V4 (day 21)
measure: Duration of fussing based on a crying-type classification of the audio recording
timeFrame: 24 hours after V1 (day 0), V2 (day 7), V3 (day 14) and for 3 days prior to V4 (day 21)
measure: Duration of crying and fussing combined based on a crying-type classification of the audio recording
timeFrame: 24 hours after V1 (day 0), V2 (day 7), V3 (day 14) and for 3 days prior to V4 (day 21)
measure: Crying and fussing comparison between the structured infant crying and fussing diary and the crying-type classification of the recording of infant crying/fussing across the intervention
timeFrame: V1 (day 0), V2 (day 7), V3 (day 14) and V4 (day 21)
measure: Maternal Postpartum depression/ anxiety
timeFrame: V1 (day 0) and V4 (day 21)
Locations:
city: Bari
country: Italy
facility: Ospedale Pediatrico Giovanni XXIII, Policlinico di Bari
city: Milano
country: Italy
facility: ASST FBF Sacco
city: Palermo
country: Italy
facility: AOUP Paolo Giaccone
city: Pisa
country: Italy
facility: Azienda Ospedaliero -Universitaria Pisana
city: Murcia
country: Spain
facility: Centro de Salud El Ranero
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago de Compostela
city: Sevilla
country: Spain
facility: Unidad de Estudios e Investigación IHP
Study officials:
References: