Synbiotic Supplement for Colic

Overseen By Stephen VanDien, PhD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Persephone Biosciences

Must not be taking: Probiotics, Antibiotics, Pancreatic enzymes, others

Disqualifiers: Congenital malformations, Infections, Gastroesophageal reflux, others

Compensation: Varies

Number of Visits: 7

Duration: 4 weeks

200 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Participants must stop taking certain medications and supplements before joining the trial. Specifically, infants and toddlers cannot have taken probiotic supplements, antibiotics, or medications affecting digestion, stool, growth, or microbiome within three months prior to enrollment.

What data supports the effectiveness of the treatment Synbiotic Supplement for colic?

Research indicates that synbiotics, which combine probiotics and prebiotics, can help reduce crying time in infants with colic by improving gut health. Specifically, studies have shown that manipulating gut bacteria with synbiotics can lead to noticeable improvements in colic symptoms. ^{1 2 3 4 5}

Is the Synbiotic Supplement safe for use in humans?

The Synbiotic Supplement, which includes a mix of beneficial bacteria, was tested in colicky babies and found to be safe with no reported adverse effects. Another study on a similar probiotic mixture also reported it as safe and well tolerated in infants. ^{2 6 7 8 9}

How does the synbiotic supplement treatment for colic differ from other treatments?

The synbiotic supplement for colic is unique because it combines multiple strains of beneficial bacteria (probiotics) with prebiotics (substances that promote the growth of good bacteria) to improve gut health, which is different from traditional treatments like simethicone that only aim to reduce gas. This approach has shown a significant reduction in crying duration and frequency in colicky babies compared to simethicone. ^{1 2 5 6 9}

What is the purpose of this trial?

Background and Significance: Bifidobacterium longum subspecies infantis (B. infantis) and other infant associated Bifidobacterium (such as Bifidobacterium longum subspecies longum and Bifidobacterium breve) are known to be important bacteria in the infant gut microbiome. A lack of Bifidobacterium in the infant gut may lead to disordered development of the infant microbiome and immune system, which can contribute to the development of gastrointestinal issues, pathogenic infections, and immune-related conditions including allergic disease and autoimmune disorders. The investigators hypothesize that establishing Bifidobacterium in the infant gut through delivery of a synbiotic, containing bifidobacterium and human milk oligosaccharides (HMOs; Bifidobacterium's primary nutrient source) may modulate the microbiome and correct this disruption. Research Question: Does synbiotic supplementation on infants and toddlers of various ages alter the gut microbiome as measured by GI-tolerance, fecal microbiome composition, and fecal metabolic profile? Objectives: * Demonstrate shifts in microbiome composition and metabolism * Demonstrate tolerance by observing neutral or positive shifts in GI related behaviors Study Design Overview: Participants Infants aged 2-24 months will be enrolled to evaluate the ability of a synbiotic (human milk oligosaccharide + a Bifidobacterium blend (B. infantis, B. longum, and B. breve)) to modulate the gut microbiome. Infants will be randomly split into two cohorts, one that receives synbiotic supplementation and one that receives a placebo control (lactose). Initially, only ages 12-24 months will be enrolled (first 25 participants), and a safety review will be performed prior to enrolling younger infants. Cohorts * Cohort 1 (supplementation) participants will be aged 2 months to 24 months. They will receive synbiotic supplementation for 1 month. * Cohort 2 (no supplementation) participants will be aged 2 months to 24 months. Will receive placebo (lactose) over the course of 1 month. Design Caretakers will be recruited and screened using an online questionnaire to determine eligibility and cohort assignment. They will give consent using an online one-party consent form (Appendix 1). Participants will be distributed randomly between cohorts 1 and 2. Participants will be shipped the synbiotic or placebo (lactose) and a set of stool sampling kits. Calls with the participant will take place throughout the study as necessary to explain participant responsibilities and ensure compliance. Two sample types will be collected during the study, a full fecal sample and a DNA/RNA tube only. The full fecal sample will be collected at the beginning and end of supplementation and the DNA/RNA tube only will be collected at all other time points. Samples will be collected at supplementation start, one week after supplementation, four weeks after supplementation start (coinciding with the end of supplementation) and 6 weeks after supplementation start (coinciding with a 2 week washout period). Journals and questionnaires will be used for the duration of supplementation as well as 2 weeks before and after to assess the impact of supplementation. Laboratory Assessments: Stool samples will be obtained for each subject. The first sample will be taken before supplementation start. Additional samples will be collected: after 1 week of supplementation, after 1 month of supplementation, and after a 2 week period of no supplementation (a washout period). All samples will be collected at home and shipped back to Persephone Biosciences for processing. The initial sample and the sample after 4 weeks of supplementation will be full samples for metagenomic, metabolomic, and proteomic analysis. The 1 week after supplementation and 2 week post supplementation samples will be DNA/RNA tube samples for metagenomics only. Microbial whole genome sequencing, metabolite analysis, and immune profiling will be performed on stool from complete stool kits. Microbial whole genome sequencing alone will be performed on the DNA/RNA tube kits. Data Collection: Demographic data, general health information, diet and lifestyle information will be collected from the subjects (all self-reported). Journals and questionnaires will be used to evaluate the impact of the synbiotic.

Eligibility Criteria

This trial is for infants and toddlers aged 2-24 months who suffer from colic. Initially, only those aged 12-24 months will be included until a safety review allows younger participants. Infants with certain health conditions or dietary restrictions may not qualify.

Inclusion Criteria

The PI considers the Caregiver likely to adequately comply with the study protocol requirements based on demonstrated compliance with initial questionnaires and agreement to complete all diaries

- Legal Guardian of the Infant

- Reads, writes, and speaks English

Exclusion Criteria

I am not taking any medications or supplements that affect my condition.

- Exposure to COVID-19

My microbiome is being considered for this study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Online questionnaire

Treatment

Participants receive daily synbiotic supplementation or placebo for 1 month

4 weeks

Home-based sample collection at start, 1 week, and 4 weeks

Washout

Participants undergo a 2-week washout period with no supplementation

2 weeks

Home-based sample collection at 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Journals and questionnaires

Treatment Details

Interventions

• Synbiotic Supplement

Trial Overview The study tests if a synbiotic supplement (a mix of Bifidobacterium and human milk oligosaccharides) can positively change the gut microbiome compared to a lactose placebo over one month. Participants are randomly assigned to either the synbiotic or placebo group.

Participant Groups

Group I: Synbiotic Supplement Active Control 1 Intervention

Participants aged 2 months to 24 months will receive daily synbiotic supplementation (probiotic+ prebiotic) for 1 month

Group II: Lactose Placebo Group 1 Intervention

Participants aged 2 months to 24 months will receive daily placebo (lactose) for 1 month

Who Is Running the Clinical Trial?

Persephone Biosciences

Lead Sponsor

Trials

6

Recruited

6,100+

Findings from Research

The lactose-reduced synbiotic formula significantly decreased crying time in infants with colic by an average of 2.7 hours compared to only 1.2 hours in the control group, indicating its efficacy in managing colic symptoms.

Parents reported a significant improvement in quality of life (QoL) for both themselves and their infants when using the intervention formula, with greater improvements noted compared to the control group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovative Dietary Intervention Answers to Baby Colic. Xinias, I., Analitis, A., Mavroudi, A., et al.[2020]

Lactobacillus reuteri DSM17938 significantly reduces crying and fussing time in breastfed infants with colic, with an average decrease of 25.4 minutes compared to a placebo group, based on a meta-analysis of 345 infants.

The probiotic was found to be nearly twice as effective in achieving treatment success in breastfed infants, but its effectiveness in formula-fed infants remains unclear and requires further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactobacillus reuteri to Treat Infant Colic: A Meta-analysis. Sung, V., D'Amico, F., Cabana, MD., et al.[2022]

A systematic review of five randomized controlled trials found that the probiotic Lactobacillus reuteri significantly reduces crying and fussing time in breastfed infants with colic, with a 2.3-fold greater chance of improvement compared to controls.

Probiotic supplementation with L. reuteri was shown to be safe, with no reported adverse events, suggesting it is a viable option for managing infantile colic in breastfed infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotics for the Treatment of Infantile Colic: A Systematic Review. Schreck Bird, A., Gregory, PJ., Jalloh, MA., et al.[2022]

Lactobacillus reuteri DSM 17938 significantly improved treatment effectiveness for infantile colic, reducing crying time at two and three weeks, based on a meta-analysis of six randomized controlled trials involving 423 infants.

The treatment was found to be safe, with no adverse effects on infants' growth measurements, but its benefits may diminish over time as infants naturally improve, highlighting the need for further high-quality studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of the Probiotic Bacterium Lactobacillus reuteri DSM 17938 for Infantile Colic: A Meta-Analysis of Randomized Controlled Trials. Xu, M., Wang, J., Wang, N., et al.[2022]

In a clinical trial involving 50 breastfed infants with colic, a synbiotic treatment significantly reduced crying time, with 82.6% of infants showing improvement at day 7 compared to 35.7% in the placebo group.

By day 30, the synbiotic group maintained a higher treatment success rate of 87% versus 46% for placebo, and no complications were reported from the synbiotic use, indicating it is a safe and effective option for managing infant colic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synbiotic in the management of infantile colic: a randomised controlled trial. Kianifar, H., Ahanchian, H., Grover, Z., et al.[2022]

In a study of 87 infants with colic, a multi-strain synbiotic significantly reduced crying days and evening crying duration compared to simethicone, with responder rates of 72% and 85% respectively, indicating its potential efficacy in treating infantile colic.

Both treatments were safe, with no adverse effects reported, suggesting that the multi-strain synbiotic could be a promising option for further research in managing colicky infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a nine-strain bacterial synbiotic compared to simethicone in colicky babies - an open-label randomised study. Piątek, J., Bernatek, M., Krauss, H., et al.[2021]

In a pilot study involving 184 infants, daily supplementation with Lactobacillus rhamnosus GG (LGG) did not significantly reduce the incidence of colic compared to a control group, with colic rates of 9.8% in the LGG group versus 5.4% in the control group.

The study found no significant differences in colic diagnosis rates by either parent-reported symptoms or physician diagnosis, indicating that LGG supplementation is not effective in preventing colic in infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Analysis of Early Lactobacillus rhamnosus GG for Infant Colic Prevention. Cabana, MD., McKean, M., Beck, AL., et al.[2022]

In a study involving 150 colicky infants over 28 days, the probiotic Bifidobacterium breve CECT7263 significantly reduced daily crying time more effectively than simethicone, showing results as early as the first week.

B. breve CECT7263 not only decreased crying but also improved sleep quality for infants and enhanced parental mood, demonstrating its safety and efficacy as a treatment for infantile colic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Bifidobacterium breve CECT7263 for infantile colic treatment: an open-label, parallel, randomised, controlled trial. Maldonado-Lobón, JA., Blanco-Rojo, R., Maldonado, J., et al.[2021]

In a study of 53 exclusively breastfed infants with colic, those treated with a probiotic-mixture experienced significantly less crying time per day compared to the placebo group, indicating its effectiveness in reducing symptoms of colic.

The probiotic-mixture was found to be safe, with no reported adverse events, and it also improved the quality of life for parents, suggesting a positive impact on both infants and their families.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of a Probiotic-Mixture for the Treatment of Infantile Colic: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial with Fecal Real-Time PCR and NMR-Based Metabolomics Analysis. Baldassarre, ME., Di Mauro, A., Tafuri, S., et al.[2018]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Innovative Dietary Intervention Answers to Baby Colic. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Lactobacillus reuteri to Treat Infant Colic: A Meta-analysis. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Probiotics for the Treatment of Infantile Colic: A Systematic Review. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of the Probiotic Bacterium Lactobacillus reuteri DSM 17938 for Infantile Colic: A Meta-Analysis of Randomized Controlled Trials. [2022]

5. Australia pubmed.ncbi.nlm.nih.gov

Synbiotic in the management of infantile colic: a randomised controlled trial. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of a nine-strain bacterial synbiotic compared to simethicone in colicky babies - an open-label randomised study. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Pilot Analysis of Early Lactobacillus rhamnosus GG for Infant Colic Prevention. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of Bifidobacterium breve CECT7263 for infantile colic treatment: an open-label, parallel, randomised, controlled trial. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of a Probiotic-Mixture for the Treatment of Infantile Colic: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial with Fecal Real-Time PCR and NMR-Based Metabolomics Analysis. [2018]