Inulin for Traumatic Brain Injury

Overseen By Christopher Danesi, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The University of Texas Medical Branch, Galveston

Disqualifiers: Heart, liver, kidney, blood, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

130 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

What data supports the effectiveness of the treatment Inulin for Traumatic Brain Injury?

Research shows that inulin, a type of prebiotic fiber, can help improve recovery from mild traumatic brain injury by promoting the growth of beneficial gut bacteria, which in turn can enhance brain health and function. In studies with mice, inulin was found to restore blood flow in the brain and improve brain structure after injury. ^{1 2 3 4 5}

Is inulin safe for humans?

Inulin, a type of prebiotic fiber, is generally considered safe for humans and has been shown to promote the growth of beneficial gut bacteria and improve bowel function. Studies have found it beneficial for gut health in a wide age range, from infants to the elderly, without significant safety concerns. ^{1 3 4 6 7}

How does the treatment Inulin differ from other treatments for traumatic brain injury?

Inulin is unique because it targets gut health by promoting beneficial bacteria and increasing short-chain fatty acids, which can help reduce inflammation and improve brain recovery after a traumatic brain injury. Unlike other treatments, it focuses on mitigating gut dysbiosis (imbalance of gut bacteria) to protect brain structure and function, and there are currently no standard treatments for mild traumatic brain injury. ^{1 4 8 9 10}

Research Team

Randall Urban, MD

Principal Investigator

University of Texas

Ana Durand, MD

Principal Investigator

Moody Neurorehabilitation Institute

Eligibility Criteria

This trial is for individuals in post-acute residential neurorehabilitation after a traumatic brain injury. It's designed to see if their gut bacteria (microbiome) can be altered by a dietary fiber called Inulin, which might help with fatigue and thinking problems.

Inclusion Criteria

Willing and able to provide consent (with LAR if needed)

Have a family member who is admitted to Moody Neurorehabilitation Institute for care OR is working at Moody Neurorehabilitation Institute

My injury occurred less than 6 months ago.

Exclusion Criteria

I have active diverticular disease.

I have not had a stroke in the last 6 months.

Pregnancy or becoming pregnant during the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily oral inulin supplementation (4g 2x daily) during inpatient post-acute neurorehabilitation

6 weeks

Regular visits during inpatient stay

Follow-up

Participants are monitored for changes in gut microbiome and neurologic symptoms after discontinuation of inulin

6 months

Periodic assessments at 3 and 6 months

Long-term Follow-up

Participants' fatigue and cognition are assessed using the Fatigue and Altered Cognition Scale

6 months

Treatment Details

Interventions

• Inulin

Trial Overview The study tests whether taking Inulin, a type of dietary fiber, changes the gut microbiome and improves neurological symptoms like fatigue and cognition in people recovering from traumatic brain injuries.

Participant Groups

Group I: Community Controls Active Control 1 Intervention

Community Control subjects will not receive intervention.

Group II: Brain Injury Patients - no intervention Active Control 1 Intervention

Brain injury patients receiving residential standard of care post-acute neurorehabilitation.

Group III: Brain Injury Patients - inulin intervention Active Control 1 Intervention

Brain injury patients receiving residential standard of care post-acute neurorehabilitation plus 42 days of daily oral inulin supplementation (4g 2x daily).

Inulin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Inulin for:

• Dietary supplement
• Prebiotic

Approved in United States as Inulin for:

• Dietary supplement
• Prebiotic

Approved in Canada as Inulin for:

• Dietary supplement
• Prebiotic

Approved in Japan as Inulin for:

• Dietary supplement
• Prebiotic

Approved in China as Inulin for:

• Dietary supplement
• Prebiotic

Approved in Switzerland as Inulin for:

• Dietary supplement
• Prebiotic

Who Is Running the Clinical Trial?

The University of Texas Medical Branch, Galveston

Lead Sponsor

Trials

263

Recruited

55,400+

The Moody Foundation

Collaborator

Trials

5

Recruited

210+

Findings from Research

Mild traumatic brain injury (mTBI) causes significant changes in the gut microbiome, leading to dysbiosis that can worsen brain health, with these changes peaking at 1.5 months post-injury in a study involving male mice over a 3-month recovery period.

Feeding prebiotic inulin after the injury improved gut microbiome composition by increasing beneficial bacteria and restoring cerebral blood flow, suggesting that dietary interventions could enhance recovery from mTBI and may lead to new treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inulin Supplementation Mitigates Gut Dysbiosis and Brain Impairment Induced by Mild Traumatic Brain Injury during Chronic Phase. Yanckello, LM., Fanelli, B., McCulloch, S., et al.[2023]

In a study of 46 neurocritical care patients, the enteric formula with prebiotic content (EFPC) led to significantly higher total energy, carbohydrate, protein, lipid, and fluid intake compared to the standard enteral formula (SEF), suggesting better nutritional support during critical care.

Patients receiving EFPC showed a non-significant trend towards achieving target nutritional doses more frequently and earlier, along with a significantly lower rate and faster improvement of diarrhea compared to those on SEF, highlighting potential benefits of prebiotics in enteral nutrition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of standard enteral formula versus enteric formula with prebiotic content in nutrition therapy: A randomized controlled study among neuro-critical care patients. Tuncay, P., Arpaci, F., Doganay, M., et al.[2019]

In a 3-month randomized, placebo-controlled trial involving 24 obese patients, the intake of inulin-type fructans (ITF) significantly increased levels of beneficial gut bacteria, specifically Bifidobacterium, and reduced fecal calprotectin, a marker of gut inflammation.

The study suggests that ITF may help improve gut health in obese individuals by decreasing inflammation and potentially influencing gut microbiota-derived metabolites, although it did not significantly change short-chain fatty acid levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prebiotic dietary fibre intervention improves fecal markers related to inflammation in obese patients: results from the Food4Gut randomized placebo-controlled trial. Neyrinck, AM., Rodriguez, J., Zhang, Z., et al.[2022]

Feeding prebiotic inulin to young mice before a closed head injury significantly reduced harmful bacteria and increased beneficial short-chain fatty acid-producing bacteria, which helped maintain gut health after the injury.

Inulin treatment improved recovery outcomes by protecting cerebral blood flow and white matter integrity, suggesting it could be a promising intervention for individuals at risk of mild traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inulin supplementation prior to mild traumatic brain injury mitigates gut dysbiosis, and brain vascular and white matter deficits in mice. Yanckello, LM., Chang, YH., Sun, M., et al.[2023]

Inulin-type fructans (ITF) have been shown to positively influence the intestinal microbiota by increasing beneficial bacteria such as Bifidobacterium and Lactobacillus, which can lead to improved gut health and function.

ITF intake is associated with several health benefits, including better intestinal barrier function, improved insulin sensitivity, lower triglycerides, enhanced mineral absorption, and increased feelings of fullness, although more research is needed to understand how chain length affects these outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Prebiotic Potential of Inulin-Type Fructans: A Systematic Review. Hughes, RL., Alvarado, DA., Swanson, KS., et al.[2023]

Chicory-derived inulin-type fructans, consumed at doses of 3-20 g/day, significantly increase the abundance of beneficial gut bacteria, specifically Bifidobacterium, in a diverse population of 2525 participants across 50 studies.

These fructans not only promote gut health by enhancing Bifidobacterium levels but also improve bowel function in healthy individuals, although their effects were less pronounced in those with gastrointestinal disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of chicory-derived inulin-type fructans on abundance of Bifidobacterium and on bowel function: a systematic review with meta-analyses. Nagy, DU., Sándor-Bajusz, KA., Bódy, B., et al.[2022]

In a review of 19 randomized controlled trials involving 777 participants, inulin-type fructan (ITF) supplementation showed limited effects on appetite and energy intake, with most studies indicating no significant changes.

However, there is some evidence suggesting that long-term ITF supplementation may help reduce body weight, particularly in nonobese adolescents and some adults, indicating potential benefits for weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of inulin-type fructans on appetite, energy intake, and body weight in children and adults: systematic review of randomized controlled trials. Liber, A., Szajewska, H.[2018]

Fructans, such as fructo-oligosaccharides and inulin, were found to directly influence inflammatory responses in endotoxemic mice, promoting the production of beneficial short-chain fatty acids like acetate and propionate, challenging previous beliefs about their microbiota-independent effects.

Long-term intake of prebiotic fibers reduced bacterial load in the spleen and lymph nodes but did not improve short-chain fatty acid synthesis or epithelial barrier function impaired by LPS, indicating that while these fibers have anti-inflammatory properties, their effects on gut health may vary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microbiota-related effects of prebiotic fibres in lipopolysaccharide-induced endotoxemic mice: short chain fatty acid production and gut commensal translocation. [2021]

Combining native chicory inulin with 2'-fucosyllactose (2'-FL) enhances the fermentation process in infant gut microbiota, leading to increased production of beneficial compounds like acetate and lactate.

The fermentation products from these non-digestible carbohydrates (NDCs) have varying immune-modulatory effects, suggesting that tailored formulations could be beneficial for infants with different immune system conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chicory inulin enhances fermentation of 2'-fucosyllactose by infant fecal microbiota and differentially influences immature dendritic cell and T-cell cytokine responses under normal and Th2-polarizing conditions. Akkerman, R., Logtenberg, MJ., Beukema, M., et al.[2023]

Inulin, particularly long-chain inulin, has been shown to reduce inflammation and endotoxemia in mice fed a high-fat diet by promoting beneficial gut bacteria like Bifidobacterium and Lactobacillus.

The study suggests that dietary inulin can be an effective prebiotic strategy to combat the negative health effects of high-fat diets by enhancing the production of short-chain fatty acids and improving gut microbiota balance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inulin with different degrees of polymerization protects against diet-induced endotoxemia and inflammation in association with gut microbiota regulation in mice. Li, LL., Wang, YT., Zhu, LM., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Inulin Supplementation Mitigates Gut Dysbiosis and Brain Impairment Induced by Mild Traumatic Brain Injury during Chronic Phase. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Use of standard enteral formula versus enteric formula with prebiotic content in nutrition therapy: A randomized controlled study among neuro-critical care patients. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

Prebiotic dietary fibre intervention improves fecal markers related to inflammation in obese patients: results from the Food4Gut randomized placebo-controlled trial. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Inulin supplementation prior to mild traumatic brain injury mitigates gut dysbiosis, and brain vascular and white matter deficits in mice. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

The Prebiotic Potential of Inulin-Type Fructans: A Systematic Review. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Effect of chicory-derived inulin-type fructans on abundance of Bifidobacterium and on bowel function: a systematic review with meta-analyses. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of inulin-type fructans on appetite, energy intake, and body weight in children and adults: systematic review of randomized controlled trials. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Microbiota-related effects of prebiotic fibres in lipopolysaccharide-induced endotoxemic mice: short chain fatty acid production and gut commensal translocation. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Chicory inulin enhances fermentation of 2'-fucosyllactose by infant fecal microbiota and differentially influences immature dendritic cell and T-cell cytokine responses under normal and Th2-polarizing conditions. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Inulin with different degrees of polymerization protects against diet-induced endotoxemia and inflammation in association with gut microbiota regulation in mice. [2021]