The Probiotic Study: Using Bacteria to Calm Your Mind

Probiotic Treatment: The Role of the Gut Microbiome in Childhood Abdominal Pain and Anxiety

The investigators seek to conduct the first open-label trial of probiotics in young children to reduce their anxiety and abdominal pain. Likewise, the investigators aim to assess the feasibility and efficacy of this treatment and to elucidate the enteric microbiota in the middle-lower GI tract. Self-report measures and a laboratory task will be collected from children, ages 9-13 years of age, and self-report measures from their primary caregivers prior to and following a 30-day probiotic administration. Children who score above cutoff in anxiety and/or abdominal pain meet the inclusion criteria for this study. Because of limited sample size and the iterative nature of intervention development, criteria for success at the pilot phase are based primarily on clinical rather than statistical criteria. The study personnel will do their best to keep and ensure the privacy and confidentiality of our participants; however, some of the risks of this study may include psychological discomfort, legal risks, and loss of confidentially.

Study Overview

• Status: Completed
• Conditions: Abdominal Pain; Anxiety
• Intervention / Treatment: Drug: Lactobacillus rhamnosus

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27701
      • Duke Center for Developmental Epedimiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 13 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Participants need to meet the criteria for functional abdominal pain as specified by the Rome III:

Scenario #1 Criteria for inclusion

1. In the last 2 months, how often did the child have pain or an uncomfortable feeling in the upper abdomen above the belly button? If ≥ 8 (or if the combination of #1 and #2 is ≥8)
2. In the last 2 months, how often did the child have pain or an uncomfortable feeling in the upper abdomen below the belly button? If ≥ 8 (or if the combination of #1 and #2 is ≥8)

Scenario #2 Criteria for inclusion 3. In the last 2 months, when the child hurt or felt uncomfortable above (below) the belly button, how often did your child miss school or stop activities? If #1 and #2 is ≥ 2 (or if the combination of #1 and #2 is ≥2) and #3 is ≥ 25% of the time.

They also have to be at or above cutoff (i.e. TS>= 55) for Beck Youth Inventory (BYI) which can be determined by finding the corresponding raw score, gender, and age on Appendix A in the BYI manual.

Exclusion Criteria:

1. Participants with immune disorders will be automatically excluded from this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Lactobacillus rhamnosus; The investigators will use Culturelle®, a probiotic composed of the micro-organisms Lactobacillus GG. This formulation has been used for the treatment of gastrointestinal inflammation in numerous clinical trials. Dosing will follow the manufacturer's recommendation for children (1 capsule/packet per day), and will be monitored by Dr. Patrick Seed from the department of pediatrics. Weekly side effects and clinical changes will be monitored by both study therapist and caregiver using the Children's Global Assessment Scale and the Clinical Global Impression Scale (Severity, Improvement, and Efficacy). The intervention duration is 30 days.

Drug: Lactobacillus rhamnosus; The investigators will use Culturelle®, a probiotic composed of the micro-organisms Lactobacillus GG. This formulation has been used for the treatment of gastrointestinal inflammation in numerous clinical trials. Dosing will follow the manufacturer's recommendation for children (1 capsule/packet per day), and will be monitored by the study Co-PI, Dr. Seed. Weekly side effects and clinical changes will be monitored by both study therapist and caregiver using the Children's Global Assessment Scale and the Clinical Global Impression Scale (Severity, Improvement, and Efficacy). The treatment duration is 30 days.; Other Names: Culturelle Kids

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Child Abdominal Pain Rating	Child and parent report is used to obtain ratings of pain intensity on a 0-12 scale. A lower score equates to lower pain intensity. Ratings are obtained for a one-week period pre and post intervention, and measured 3 times daily. Pre-treatment assessments took place days 1-7, participants were treated days 8-36, and post-intervention assessments were completed days 37-44. All time points will be averaged and combined across raters (child and parent) resulting in an average pain severity rating pre and post-treatment. The change in this average rating will be assessed as pain severity outcome. This measure was averaged with the pain frequency average score (see Primary Outcome 2) to result in one primary severity/frequency pain rating pre and post treatment. The change in this combined measure is our primary index of change.	One week pre-intervention (Study Day 1), One week post-intervention (Study Day 44)
Change in Child Abdominal Pain Frequency	Child and parent report is used to obtain ratings of pain frequency, the number of distinct occasions that pain was reported. Frequency was obtained for a one-week period pre and post intervention, and measured 3 times daily during these intervals. During the 30-day intervention, end of day frequencies were made. Pre-treatment assessments took place days 1-7, participants were treated days 8-36, and post-intervention assessments were completed days 37-44. The average number of episodes across these time points will be calculated pre and post treatment. The change in this average frequency from pre to post treatment will be the measure of change.	One week pre-intervention (Study Day 1), One week post-intervention (Study Day 44)
Change in Child Anxiety Symptoms	We report the change in magnitude of self-reported state anxiety derived from summed raw scores obtained through the six-item short-form of the state scale of the Spielberger State-Trait Anxiety Inventory at baseline and 30 days from baseline. Scores in the scale range from 6-24, with greater scores indicating worse anxiety. We obtained the summed raw scores after reverse scoring items 1, 4 & 5.	Baseline and 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Adherence to Treatment	Adherence was calculated as: ("the days probiotic was taken"/"total number of days of treatment") x 100, with results ranging from 0% (no probiotics taken at all) to 100% (probiotics taken 30 days out of the 30 day-treatment period). Researcher will subtract the number of pills/packets taken from the total amount.	30 days
Change in Relative Quantities of Taxa Among Groups Relative to Probiotic Administration		Baseline and 30 days
Change in Alpha Diversity		Baseline and 30 days
Change in Beta Diversity (PCoA)		Baseline and 30 days
Change in Trait-associated Co-functional Modules of Organisms		Baseline and 30 days
Change in Salivary Cortisol (ug/dL)		Baseline and 30 days
Change in Heart Rate	Beats per minute (Bpm)	Baseline and 30 days

Collaborators and Investigators

• Sponsor: Nancy Zucker
• Investigators: Principal Investigator: Nancy Zucker, Ph.D., Duke University

Publications and helpful links

General Publications

• Marteau TM, Bekker H. The development of a six-item short-form of the state scale of the Spielberger State-Trait Anxiety Inventory (STAI). Br J Clin Psychol. 1992 Sep;31(3):301-6. doi: 10.1111/j.2044-8260.1992.tb00997.x. Erratum In: Br J Clin Psychol. 2020 Jun;59(2):276.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 8, 2016
• Primary Completion (ACTUAL): September 18, 2017
• Study Completion (ACTUAL): September 18, 2017

Study Registration Dates

• First Submitted: January 22, 2016
• First Submitted That Met QC Criteria: March 11, 2016
• First Posted (ESTIMATE): March 17, 2016

Study Record Updates

• Last Update Posted (ACTUAL): January 3, 2019
• Last Update Submitted That Met QC Criteria: December 12, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Signs and Symptoms, Digestive; Abdominal Pain
• Other Study ID Numbers: Pro00063870

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Given the pilot nature of the study, resulting data may not be appropriate for sharing within a larger data repository. We will change this policy if we learn otherwise.