The Probiotic Study: Using Bacteria to Calm Your Mind

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02711800

Enrollment

Registered

2016-03-17

Start date

2016-11-08

Completion date

2017-09-18

Last updated

2019-01-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Anxiety, Abdominal Pain

Brief summary

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.

Interventions

DRUGLactobacillus 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.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

9 Years to 13 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Change in Child Abdominal Pain Rating	One week pre-intervention (Study Day 1), One week post-intervention (Study Day 44)	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.
Change in Child Abdominal Pain Frequency	One week pre-intervention (Study Day 1), One week post-intervention (Study Day 44)	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.
Change in Child Anxiety Symptoms	Baseline and 30 days	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.

Secondary

Measure	Time frame	Description
Change in Beta Diversity (PCoA)	Baseline and 30 days	—
Change in Trait-associated Co-functional Modules of Organisms	Baseline and 30 days	—
Percentage of Adherence to Treatment	30 days	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.
Change in Heart Rate	Baseline and 30 days	Beats per minute (Bpm)
Change in Salivary Cortisol (ug/dL)	Baseline and 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	—

Countries

United States

Participant flow

Participants by arm

Arm	Count
Lactobacillus Rhamnosus The investigators will use Culturelle®, a probiotic composed of the micro-organisms Lactobacillus GG. 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. The intervention duration is 30 days.	9
Total	9

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Lost to Follow-up	1
Overall Study	Withdrawal by Subject	1

Baseline characteristics

Characteristic	Lactobacillus Rhamnosus
Age, Continuous	11.746 years STANDARD_DEVIATION 0.753
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Pain intensity	1.11 units on a scale STANDARD_DEVIATION 1.04
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	3 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	6 Participants
Sex: Female, Male Female	4 Participants
Sex: Female, Male Male	5 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 7
other Total, other adverse events	0 / 7
serious Total, serious adverse events	0 / 7

Outcome results

Primary

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.

Time frame: One week pre-intervention (Study Day 1), One week post-intervention (Study Day 44)

Population: Data was missing for one participant

Arm	Measure	Value (MEAN)	Dispersion
Lactobacillus Rhamnosus	Change in Child Abdominal Pain Frequency	0.40 pain episodes	Standard Deviation 0.61

Primary

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.

Time frame: One week pre-intervention (Study Day 1), One week post-intervention (Study Day 44)

Population: Data was missing for one participant

Arm	Measure	Value (MEAN)	Dispersion
Lactobacillus Rhamnosus	Change in Child Abdominal Pain Rating	0.36 units on a scale	Standard Deviation 0.58

Primary

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.