Clinical trial NCT04949607: Traumatic Brain Injury and the Gut Microbiome
Official title: Traumatic Brain Injury and the Gut Microbiome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Brain Injury, Chronic
Brain Injuries, Traumatic
Lead sponsor: Centre for Neuro Skills
Sponsor class: INDUSTRY
Collaborators: name: University of Texas
First posted: 2021-07-02
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be administered 1-4 grams of Inulin twice daily for 3 months.
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to determine whether administration of a prebiotic, inulin, can improve the symptom complex associated with traumatic brain injury and whether inulin administration can alter the bacteria that live in the gut.

Detailed description: The investigators will study subjects (aged 18-70 years) with a history of moderate/severe traumatic brain injury (n=10) and healthy controls (aged 18-70 years) (n=10). All subjects will undergo a 3-month intervention of oral inulin treatment. The traumatic brain injury subjects will be administered oral inulin twice daily for 3 months. Testing including cognitive function assessment (Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and questionnaires of fatigue, mood and quality of life and sleep will occur at month 0, 3 and 6. Blood sampling for measurement of amino acid levels, hormones, short chain fatty acids and markers of neuroinflammation will be drawn before and 90 minutes (+/- 10 minutes) after a standardized meal will occur at month 0 and month 3. In addition, fecal samples for analysis of the GI microbiome will be collected at month -1, month 0, month 1, month 2, month 3, and month 6 along with an assessment of gastrointestinal health. Traumatic brain injury subjects will be selected from residents at a long term residential rehabilitation center. Healthy control subjects will be administered oral inulin twice daily with meals for 3 months. Quality of life will be assessed by questionnaires at months 0, 3 and 6. Blood sampling for measurement of amino acid levels, hormones, short chain fatty acids and markers of neuroinflammation will be drawn before and 90 minutes (+/- 10 minutes) after a standardized meal will occur at month 0 and month 3. Fecal samples will be collected at month -1, month 0, month 3 and month 6 for analysis of the GI microbiome along with an assessment of gastrointestinal health. A member of the study team will check monthly for adverse events and overall well-being and ensure compliance and ongoing consent.

Eligibility criteria: Inclusion Criteria:

-Traumatic Brain Injury

Head trauma greater than two years prior manifesting in one or more of the following:

1. Loss of consciousness
2. Post-traumatic amnesia
3. Focal neurologic deficits
4. Seizures
5. Persistent symptoms of increased arousal (e.g., difficulty falling or staying asleep, anger and hypervigilance)
6. Impairment in cognitive, social, occupational, or other important areas of functioning (e.g., problems with work and relationships)

Exclusion Criteria:

* Traumatic Brain Injury

  1. Unwilling to give consent. Patients with rights managed by Legal Authorized Representative must consent to participate in addition to consent from their legal agent
  2. \< 2 years post-injury
  3. Known allergy to study agent.
  4. Other medical condition or medication administration deemed exclusionary by the study investigators.

     Inclusion Criteria:
* Healthy Control

  1. Ages 18 to 70 years
  2. Works at Centre for Neuro Skills
  3. Participant is willing and able to give informed consent for participation in the study.

     Exclusion Criteria
* Healthy Control

  1. Subjects with a history of inflammatory bowel disease, Celiac disease or active diverticular disease.
  2. Known allergy to study agent.
  3. Other medical condition or medication administration deemed exclusionary by the study investigators.

Primary outcomes:
measure: Characterization of fecal microbiome using molecular methods at baseline
timeFrame: Baseline
measure: Characterization of fecal microbiome using molecular methods at month 1
timeFrame: month 1
measure: Characterization of fecal microbiome using molecular methods at month 2
timeFrame: month 2
measure: Characterization of fecal microbiome using molecular methods at month 3
timeFrame: month 3
measure: Characterization of fecal microbiome using molecular methods at month 6
timeFrame: month 6
Secondary outcomes:
measure: Sleep Quality as measured by Pittsburgh Sleep Quality Index at baseline
timeFrame: Baseline (month 0)
measure: Sleep Quality as measured by Pittsburgh Sleep Quality Index at month 3
timeFrame: month 3
measure: Sleep Quality as measured by Pittsburgh Sleep Quality Index at month 6
timeFrame: month 6
measure: Symptoms of Growth Hormone Deficiency measured by the questionnaire Quality of Life - Assessment of Growth Hormone Deficiency in Adults at baseline
timeFrame: Baseline (month 0)
measure: Symptoms of Growth Hormone Deficiency measured by the questionnaire Quality of Life - Assessment of Growth Hormone Deficiency in Adults at month 3
timeFrame: month 3
measure: Symptoms of Growth Hormone Deficiency measured by the questionnaire Quality of Life - Assessment of Growth Hormone Deficiency in Adults at month 6
timeFrame: month 6
measure: Depression measured by the Beck Depression Inventory-II at baseline
timeFrame: Baseline (month 0)
measure: Depression measured by the Beck Depression Inventory-II at month 3
timeFrame: month 3
measure: Depression measured by the Beck Depression Inventory-II at month 6
timeFrame: month 6
measure: Gastrointestinal Health measured by the Gastrointestinal Symptom Rating Scale at baseline
timeFrame: Baseline (month 0)
measure: Gastrointestinal Health measured by the Gastrointestinal Symptom Rating Scale at month 1
timeFrame: month 1
measure: Gastrointestinal Health measured by the Gastrointestinal Symptom Rating Scale at month 2
timeFrame: month 2
measure: Gastrointestinal Health measured by the Gastrointestinal Symptom Rating Scale at month 3
timeFrame: month 3
measure: Gastrointestinal Health measured by the Gastrointestinal Symptom Rating Scale at month 6
timeFrame: month 6
measure: Perceptual Fatigue as measured by the Brain Injury Fatigue and Altered Cognition (BIAFAC) Questionnaire at baseline
timeFrame: Baseline (month 0)
measure: Perceptual Fatigue as measured by the Brain Injury Fatigue and Altered Cognition (BIAFAC) Questionnaire at month 3
timeFrame: month 3
measure: Perceptual Fatigue as measured by the Brain Injury Fatigue and Altered Cognition (BIAFAC) Questionnaire at month 6
timeFrame: month 6
measure: Perceptual Cognition as measured by the Brain Injury Fatigue and Altered Cognition (BIAFAC) Questionnaire at baseline
timeFrame: Baseline (month 0)
measure: Perceptual Cognition as measured by the Brain Injury Fatigue and Altered Cognition (BIAFAC) Questionnaire at month 3
timeFrame: month 3
measure: Perceptual Cognition as measured by the Brain Injury Fatigue and Altered Cognition (BIAFAC) Questionnaire at month 6
timeFrame: month 6
measure: Total BIAFAC (Brain Injury Fatigue and Altered Cognition) Score as measured by the Brain Injury Fatigue and Altered Cognition (BIAFAC) Questionnaire at baseline
timeFrame: Baseline (month 0)
measure: Total BIAFAC (Brain Injury Fatigue and Altered Cognition) Score as measured by the Brain Injury Fatigue and Altered Cognition (BIAFAC) Questionnaire at month 3
timeFrame: month 3
measure: Total BIAFAC (Brain Injury Fatigue and Altered Cognition) Score as measured by the Brain Injury Fatigue and Altered Cognition (BIAFAC) Questionnaire at month 6
timeFrame: month 6
measure: Cognition as assessed by the Repeatable Battery Assessment for Neuropsychological Status (RBANS) at baseline
timeFrame: Baseline
measure: Cognition as assessed by the Repeatable Battery Assessment for Neuropsychological Status (RBANS) at month 3
timeFrame: month 3
measure: Cognition as assessed by the Repeatable Battery Assessment for Neuropsychological Status (RBANS) at month 6
timeFrame: month 6
measure: 1 methyl Histidine at baseline
timeFrame: Baseline (month 0)
measure: 1 methyl Histidine at month 3
timeFrame: month 3
measure: 3 methyl Histidine at baseline
timeFrame: Baseline (month 0)
measure: 3 methyl Histidine at month 3
timeFrame: month 3
measure: L-alpha-Aminoadipic acid at baseline
timeFrame: Baseline (month 0)
measure: L-alpha-Aminoadipic acid at month 3
timeFrame: month 3
measure: 2-Aminobutyric Acid at baseline
timeFrame: Baseline (month 0)
measure: 2-Aminobutyric Acid at month 3
timeFrame: month 3
measure: Alanine at baseline
timeFrame: Baseline (month 0)
measure: Alanine at month 3
timeFrame: month 3
measure: Asparagine at baseline
timeFrame: Baseline (month 0)
measure: Asparagine at baseline
timeFrame: month 3
measure: Arginine at baseline
timeFrame: Baseline (month 0)
measure: Arginine at month 3
timeFrame: month 3
measure: Aspartate at baseline
timeFrame: Baseline (month 0)
measure: Aspartate at month 3
timeFrame: month 3
measure: D, L-beta-Aminoisobutyric acid
timeFrame: Baseline (month 0)
measure: D, L-beta-Aminoisobutyric acid
timeFrame: month 3
measure: beta-Alanine at baseline
timeFrame: Baseline (month 0)
measure: beta-Alanine at month 3
timeFrame: month 3
measure: L-Carnosine
timeFrame: Baseline (month 0)
measure: L-Carnosine
timeFrame: month 3
measure: Citrulline at baseline
timeFrame: Baseline (month 0)
measure: Citrulline at month 3
timeFrame: month 3
measure: Cystathionine
timeFrame: Baseline (month 0)
measure: Cystathionine
timeFrame: month 3
measure: Cysteine at baseline
timeFrame: Baseline (month 0)
measure: Cysteine at month 3
timeFrame: month 3
measure: Ethanolamine at baseline
timeFrame: Baseline (month 0)
measure: Ethanolamine at month 3
timeFrame: month 3
measure: Gamma aminobutyric acid at baseline
timeFrame: Baseline (month 0)
measure: Gamma aminobutyric acid at month 3
timeFrame: month 3
measure: Glutamine at baseline
timeFrame: Baseline (month 0)
measure: Glutamine at month 3
timeFrame: month 3
measure: Glutamate at baseline
timeFrame: Baseline (month 0)
measure: Glutamate at month 3
timeFrame: month 3
measure: Glycine at baseline
timeFrame: Baseline (month 0)
measure: Glycine at month 3
timeFrame: month 3
measure: Homocysteine at baseline
timeFrame: Baseline (month 0)
measure: Homocysteine at month 3
timeFrame: month 3
measure: Histidine at baseline
timeFrame: Baseline (month 0)
measure: Histidine at month 3
timeFrame: month 3
measure: Hydroxylysine at baseline
timeFrame: Baseline (month 0)
measure: Hydroxylysine at month 3
timeFrame: month 3
measure: Hydroxyproline at baseline
timeFrame: Baseline (month 0)
measure: Hydroxyproline at month 3
timeFrame: month 3
measure: Isoleucine at baseline
timeFrame: Baseline (month 0)
measure: Isoleucine at month 3
timeFrame: month 3
measure: Leucine at baseline
timeFrame: Baseline (month 0)
measure: Leucine at month 3
timeFrame: month 3
measure: Lysine at baseline
timeFrame: Baseline (month 0)
measure: Lysine at month 3
timeFrame: month 3
measure: Methionine at baseline
timeFrame: Baseline (month 0)
measure: Methionine at month 3
timeFrame: month 3
measure: Norleucine at baseline
timeFrame: Baseline (month 0)
measure: Norleucine at month 3
timeFrame: month 3
measure: Norvaline at baseline
timeFrame: Baseline (month 0)
measure: Norvaline at month 3
timeFrame: month 3
measure: Ornithine at baseline
timeFrame: Baseline (month 0)
measure: Ornithine at month 3
timeFrame: month 3
measure: phospho-ethanolamine at baseline
timeFrame: Baseline (month 0)
measure: phospho-ethanolamine at month 3
timeFrame: month 3
measure: Phenylalanine at baseline
timeFrame: Baseline (month 0)
measure: Phenylalanine at month 3
timeFrame: month 3
measure: Proline at baseline
timeFrame: Baseline (month 0)
measure: Proline at month 3
timeFrame: month 3
measure: phospho-serine at baseline
timeFrame: Baseline (month 0)
measure: phospho-serine at month 3
timeFrame: month 3
measure: Sarcosine at baseline
timeFrame: Baseline (month 0)
measure: Sarcosine at month 3
timeFrame: month 3
measure: Serine at baseline
timeFrame: Baseline (month 0)
measure: Serine at month 3
timeFrame: month 3
measure: Taurine at baseline
timeFrame: Baseline (month 0)
measure: Taurine at month 3
timeFrame: month 3
measure: Threonine at baseline
timeFrame: Baseline (month 0)
measure: Threonine at month 3
timeFrame: month 3
measure: Tryptophan at baseline
timeFrame: Baseline (month 0)
measure: Tryptophan at month 3
timeFrame: month 3
measure: Tyrosine at baseline
timeFrame: Baseline (month 0)
measure: Tyrosine at month 3
timeFrame: month 3
measure: Valine at baseline
timeFrame: Baseline (month 0)
measure: Valine at month 3
timeFrame: month 3
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Centre for Neuro Skills
state: California
Study officials:
affiliation: Centre for Neuro Skills
name: Brent Masel, MD
role: PRINCIPAL_INVESTIGATOR
References: