Clinical trial NCT06607523: The Gut-Brain Axis During Neurorehabilitation; Prebiotic Treatment to Alter the Gut Microbiome and Neurologic Symptoms
Official title: The Gut-Brain Axis During Neurorehabilitation; Prebiotic Treatment to Alter the Gut Microbiome and Neurologic Symptoms
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Brain Injuries
Keywords: Brain Injury
Neurorehabilitation
Fatigue
Cognition
Lead sponsor: The University of Texas Medical Branch, Galveston
Sponsor class: OTHER
Collaborators: name: The Moody Foundation
First posted: 2024-09-23
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to characterize the microbiome of patients undergoing post-acute residential neurorehabilitation compared to community controls and to determine if a dietary fiber, Inulin, can create a shift in the microbiome leading to changes in fatigue and cognition.

Detailed description: The investigative research team previously described Brain Injury Associated Fatigue and Altered Cognition (BIAFAC) as a treatable syndrome that occurs in a subset of patients following traumatic brain injury (TBI). In addition to fatigue and brain fog, BIAFAC patients have altered growth hormone (GH) secretion, reduced serum amino acid levels, and an altered (dysbiotic) gut microbiome. GH treatment dramatically improves patient symptoms but is not curative; symptoms return when GH treatment ends and the associated gut dysbiosis is not corrected. In preliminary work with mouse models created using human fecal transplants from clinical BIAFAC subjects, transplanting the dysbiotic gut bacteria from BIAFAC patients alone caused fatigue, altered cognition, and dysregulated GH secretion without any trauma or head injury. These mouse models indicate that gut dysbiosis has a causative role in the development of BIAFAC by triggering both altered GH secretion and neurologic symptoms. In this clinical trial a dietary fiber, Inulin, will be administered to patients undergoing neurorehabilitation after brain injury to create a shift in their microbiome.

Specific Aims

Aim 1. Identify differences in blood and fecal microbiome biomarkers of neurorehabilitation patients.

Specific Aim 1a. Identify differences in blood and fecal microbiome biomarkers between patients entering an inpatient post-acute neurorehabilitation program and community controls.

Specific Aim 1b. Identify correlations between biomarkers (blood and fecal microbiome), demographics (e.g. age, sex), and clinical factors (e.g. medical history) of post-acute neurorehabilitation patients.

Specific Aim 1c. Document longitudinal change in blood and fecal microbiome biomarkers of patients during inpatient post-acute neurorehabilitation.

Aim 2. Determine the effect of dietary inulin supplement on patients undergoing post-acute neurorehabilitation.

Specific Aim 2a. Determine how dietary inulin supplementation impacts the gut microbiome profile and function in brain injury patients during inpatient post-acute neurorehabilitation.

Specific Aim 2b. Determine if dietary inulin supplementation affects fatigue and cognition in patients during inpatient post-acute neurorehabilitation.

Aim 3. Determine if short-term early intervention dietary inulin supplementation during post-acute neurorehabilitation affects longer-term patient-reported outcomes.

Eligibility criteria: Brain Injury Patients

Inclusion

* Ages 18 and above
* Admitted to Moody Neurorehabilitation Institute for care
* Less than 6 months post-injury
* English speaking
* Must be able to eat and drink by mouth
* Willing and able to comply with study procedures
* Willing and able to provide consent (with LAR if needed)

Exclusion

* Significant heart, liver, kidney, blood or respiratory disease
* HIV, Hepatitis B or Hepatitis C
* Pregnancy or becoming pregnant during the study
* History of inflammatory bowel disease
* History of celiac disease
* Active diverticular disease
* Known allergy to study agent
* Any medical condition that, in the opinion of the investigator, would place the subject at increased risk for participation

Community Control Subjects

Inclusion

* Ages 18 and above
* Have a family member who is admitted to Moody Neurorehabilitation Institute for care OR is working at Moody Neurorehabilitation Institute
* English speaking
* Willing and able to comply with study procedures
* Willing and able to provide consent
* FACs score ≤ 50

Exclusion

* Trauma to head in last 6 months
* Stroke in last 6 months
* Significant heart, liver, kidney, blood or respiratory disease
* HIV, Hepatitis B or Hepatitis C
* Pregnancy or becoming pregnant during the study
* History of inflammatory bowel disease
* History of celiac disease
* Active diverticular disease
* Any medical condition that, in the opinion of the investigator, would place the subject at increased risk for participation

Primary outcomes:
measure: Quantify absolute abundance of gut microbiome using using metagenomic analysis at baseline
timeFrame: baseline
measure: Quantify absolute abundance of gut microbiome using using metagenomic analysis after 42 days of inulin supplementation
timeFrame: 42 days inulin treatment
measure: Quantify absolute abundance of gut microbiome using using metagenomic analysis at 3 months of discontinuation of inulin
timeFrame: 3 months of discontinuation of inulin
measure: Quantify absolute abundance of gut microbiome using using metagenomic analysis at 6 months of discontinuation of inulin
timeFrame: 6 months of discontinuation of inulin
measure: Fold change in relative abundance of gut microbiome using using metatranscriptomic analysis from baseline to 42 days of inulin treatment
timeFrame: From baseline to 42 days of inulin treatment
measure: Fold change in relative abundance of gut microbiome using using metatranscriptomic analysis from baseline to 3 months after discontinuation of inulin treatment
timeFrame: From baseline to 3 months after discontinuation of inulin treatment
measure: Fold change in relative abundance of gut microbiome using using metatranscriptomic analysis from baseline to 6 months after discontinuation of inulin treatment
timeFrame: From baseline to 6 months after discontinuation of inulin treatment
Secondary outcomes:
measure: Fatigue and Cognition as measured by the Fatigue and Altered Cognition Scale at baseline
timeFrame: baseline
measure: Fatigue and Cognition as measured by the Fatigue and Altered Cognition Scale after 42 days of inulin treatment
timeFrame: 42 days of inulin treatment
measure: Fatigue and Cognition as measured by the Fatigue and Altered Cognition Scale at 3 months after discontinuation of inulin
timeFrame: 3 months discontinuation of inulin
measure: Fatigue and Cognition as measured by the Fatigue and Altered Cognition Scale at 6 months discontinuation of inulin
timeFrame: 6 months discontinuation of inulin
Other outcomes:
Locations:
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
Study officials:
affiliation: University of Texas
name: Randall Urban, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Moody Neurorehabilitation Institute
name: Ana Durand, MD
role: STUDY_DIRECTOR
References: