Trial Outcomes & Findings for Biological Signatures, Probiotic Among Those With mTBI and PTSD (NCT NCT02723344)

NCT ID: NCT02723344

Last Updated: 2020-08-18

Results Overview

Inflammation - Biological Signature (Blood)

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 75 participants
• Primary outcome timeframe: Baseline and approximately 10 weeks
• Results posted on: 2020-08-18

Participant Flow

Although 75 participants were consented and enrolled in the study, 31 participants met inclusion criteria and continued participation.

Participant milestones

Measure	Placebo Allocated to Placebo	L Reuteri Allocated to L reuteri
Overall Study STARTED	15	16
Overall Study COMPLETED	15	12
Overall Study NOT COMPLETED	0	4

Reasons for withdrawal

Measure	Placebo Allocated to Placebo	L Reuteri Allocated to L reuteri
Overall Study Lost to Follow-up	0	4

Baseline Characteristics

Biological Signatures, Probiotic Among Those With mTBI and PTSD

Baseline characteristics by cohort

Measure	Placebo n=15 Participants Sham Probiotic	L Reuteri n=16 Participants Probiotic	Total n=31 Participants Total of all reporting groups
Age, Continuous	36.7 years STANDARD_DEVIATION 6.2 • n=5 Participants	37.9 years STANDARD_DEVIATION 7.3 • n=7 Participants	37.4 years STANDARD_DEVIATION 6.7 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	16 Participants n=7 Participants	31 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and approximately 10 weeks

Population: A sufficient amount of plasma was not available to run CRP on 1 participant in the placebo group and 2 participants in the L reuteri group.

Inflammation - Biological Signature (Blood)

Outcome measures

Measure	Placebo n=14 Participants Allocated to Placebo	L Reuteri n=10 Participants Allocated to L reuteri
C-Reactive Protein Change	0.113 mg/L Standard Deviation 1.2	-0.625 mg/L Standard Deviation 1.1

SECONDARY outcome

Timeframe: 2 weeks and approximately 10 weeks

Population: A sufficient amount of plasma was not available to run TNF on 1 participant in the placebo group and 3 participants in the L reuteri group.

Inflammation - Biological Signature (Blood)

Outcome measures

Measure	Placebo n=14 Participants Allocated to Placebo	L Reuteri n=9 Participants Allocated to L reuteri
Tumor Necrosis Factor Change	-0.62 pg/ml Standard Deviation 1.4	-2.1 pg/ml Standard Deviation 8.2

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately 10 weeks

Population: VAS was administered at T3 therefore data was only available on participants who completed the study.

The VAS was administered during the Trier Social Stress Task (TSST). The VAS is self-reported stress response on a Likert scale (1-10). A higher score indicates greater perceived stress. In the TSST, participants are asked to give a 5-minute speech and perform a math task. The VAS was administered at the baseline of the TSST, after the Speech Task, and after the Math Task.

Outcome measures

Measure	Placebo n=15 Participants Allocated to Placebo	L Reuteri n=12 Participants Allocated to L reuteri
Visual Analog Scale TSST Baseline	4.13 score on a scale Interval 2.77 to 5.5	5.38 score on a scale Interval 3.85 to 6.9
Visual Analog Scale TSST After Speech	5.29 score on a scale Interval 4.04 to 6.54	6.25 score on a scale Interval 4.87 to 7.63
Visual Analog Scale TSST After Math	6.44 score on a scale Interval 5.06 to 7.84	7.13 score on a scale Interval 5.6 to 8.65

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 weeks and approximately 10 weeks

Population: A sufficient amount of plasma was not available to run IL6 on 1 participant in the placebo group and 3 participants in the L reuteri group.

Inflammation - Biological Signature (Blood)

Outcome measures

Measure	Placebo n=14 Participants Allocated to Placebo	L Reuteri n=9 Participants Allocated to L reuteri
Interleukin 6 Change	.22 pg/ml Standard Deviation 2.4	-.07 pg/ml Standard Deviation 7.7

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 weeks and approximately 10 weeks

Population: A sufficient amount of plasma was not available to run IL10 on 1 participant in the placebo group and 3 participants in the L reuteri group.

Inflammation - Biological Signature (Blood)

Outcome measures

Measure	Placebo n=14 Participants Allocated to Placebo	L Reuteri n=9 Participants Allocated to L reuteri
Interleukin 10 Change	0.15 pg/ml Standard Deviation 0.85	-0.23 pg/ml Standard Deviation 2.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 weeks and approximately 10 weeks

Population: A sufficient amount of plasma was not available to run IFABP on 3 participants in the placebo group and 2 participants in the L reuteri group.

Gut Permeability (Blood) - IFABP, measured by ELISA

Outcome measures

Measure	Placebo n=12 Participants Allocated to Placebo	L Reuteri n=10 Participants Allocated to L reuteri
Intestinal Fatty Acid Binding Protein (IFABP) Change	-0.09 pg/ml Standard Deviation 0.45	-0.04 pg/ml Standard Deviation 0.16

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 weeks and approximately 10 weeks

Population: A sufficient amount of plasma was not available to run DAO on 5 participants in the placebo group and 4 participants in the L reuteri group.

Gut Permeability (Blood) - DAO, measured by ELISA

Outcome measures

Measure	Placebo n=10 Participants Allocated to Placebo	L Reuteri n=8 Participants Allocated to L reuteri
D-amino Acid Oxidase (DAO) Change	-0.11 pg/ml Standard Deviation 0.24	0.03 pg/ml Standard Deviation 0.12

OTHER_PRE_SPECIFIED outcome

Timeframe: Time 1 (Baseline), Time 2 (2 weeks), and Time 3 (10 weeks)

Population: 2 participants in the L reuteri group were lost to follow at Time 2, and then 2 more participants were lost to follow at Time 3.

This measure of tolerability consists of 36 symptom descriptions organized by body parts. Participants are asked to rate if these symptoms were either "not present", "mild", "moderate", or "severe" in the past week related to supplementation. Total severity scores range 0-108. A higher severity score indicates more symptom severity. Total symptom scores range 0-36. A higher symptom score indicates more symptoms.

Outcome measures

Measure	Placebo n=15 Participants Allocated to Placebo	L Reuteri n=16 Participants Allocated to L reuteri
Generic Assessment of Side Effects-Probiotics (GASE-P) Time 1 - Severity	25.6 score on a scale Standard Deviation 13.9	28.1 score on a scale Standard Deviation 12.7
Generic Assessment of Side Effects-Probiotics (GASE-P) Time 1 - Symptom Count	14.4 score on a scale Standard Deviation 5.5	15.9 score on a scale Standard Deviation 6.4
Generic Assessment of Side Effects-Probiotics (GASE-P) Time 2 - Severity	22.1 score on a scale Standard Deviation 13.2	23.7 score on a scale Standard Deviation 8.8
Generic Assessment of Side Effects-Probiotics (GASE-P) Time 2 - Symptom Count	12.4 score on a scale Standard Deviation 6.4	15.6 score on a scale Standard Deviation 4.8
Generic Assessment of Side Effects-Probiotics (GASE-P) Time 3 - Severity	11.7 score on a scale Standard Deviation 11.3	14.3 score on a scale Standard Deviation 12.0
Generic Assessment of Side Effects-Probiotics (GASE-P) Time 3 - Symptom Count	6.5 score on a scale Standard Deviation 4.5	9.8 score on a scale Standard Deviation 8.5

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

L Reuteri

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Lisa A Brenner

Eastern Colorado Health Care System, Rocky Mountain MIRECC

Phone: 720-723-6488

Email: lisa.brenner@va.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place