Probiotics + tVNS for Cognition Improvement

Overseen By Emily Carter

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Florida

Must not be taking: Antibiotics, Probiotics

Disqualifiers: Major psychiatric illness, Opioid use, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This project uses a hybrid trial design to evaluate two biomedical interventions targeting the gut-brain axis. One intervention is portable Transcutaneous Vagus Nerve Stimulator, tVNS, that is hypothesized to stimulate the autonomic nervous system, resulting in decreased inflammation and improved cognition. The second intervention is a probiotic supplement intended to replace gut bacteria that are associated with dysbiosis in persons with HIV and alcohol consumption.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using antibiotics or probiotics.

Is the combination of probiotics and tVNS generally safe for humans?

Research on probiotics shows they can influence brain function and behavior through the gut-brain axis, and they have been used safely in various studies. However, specific safety data on the combination of probiotics with transcutaneous vagal nerve stimulation (tVNS) is not provided in the available research. ^{1 2 3 4 5}

How is the Probiotics + tVNS treatment for cognition improvement different from other treatments?

This treatment is unique because it combines probiotics, which can influence brain function through the gut-brain axis, with transcutaneous vagal nerve stimulation (tVNS), a non-invasive method that stimulates the vagus nerve to potentially enhance cognitive function. This dual approach targets both the gut microbiome and neural pathways, offering a novel way to improve cognition compared to traditional treatments. ^{1 2 3 4 6}

What data supports the effectiveness of the treatment Probiotics + tVNS for Cognition Improvement?

Research shows that probiotics can enhance cognitive function and affect brain activity through the gut-brain axis, which involves the vagus nerve. Additionally, probiotics have been found to improve cognitive impairment in both humans and animals, suggesting potential benefits for cognition improvement. ^{1 3 4 6 7}

Who Is on the Research Team?

Eric Porges, PhD

Principal Investigator

University of Florida

Robert L Cook, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for English or Spanish speakers aged 35-70 who consume alcohol, have a CD4 count over 350, and some cognitive impairment. It's not for those with recent opioid use, past-year intensive addiction treatment, current antibiotic or probiotic use, major psychiatric illness, or very high alcohol consumption.

Inclusion Criteria

I have difficulty with memory or thinking clearly.

I am between 35 and 70 years old.

Current CD4>350

Exclusion Criteria

Current probiotic use

Diagnosed major psychiatric illness

I have not been in intensive treatment for addiction in the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the Visbiome probiotic supplement or Transcutaneous Vagal Nerve Stimulation (tVNS) to target the gut-brain axis

12 weeks

Multiple visits for neuropsychological tests and stool sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Probiotic Supplement
• Transcutaneous Vagal Nerve Stimulation (tVNS)

Trial Overview The study tests two interventions: a portable Transcutaneous Vagus Nerve Stimulator (tVNS) thought to reduce inflammation and boost cognition; and a probiotic supplement aimed at improving gut health in people with HIV affected by alcohol.

How Is the Trial Designed?

Group I: Dietary Supplement (e.g., vitamins, minerals) Experimental Treatment 1 Intervention

Visbiome probiotic supplement

Group II: Device (including sham) Active Control 1 Intervention

Transcutaneous Vagal Nerve Stimulation (tVNS)

Probiotic Supplement is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Probiotics for:

• Supportive therapy for gastrointestinal health
• Prevention of antibiotic-associated diarrhea

Approved in United States as Probiotics for:

• Dietary supplement for gut health
• Prevention of necrotizing enterocolitis in preterm infants

Approved in Canada as Probiotics for:

• Natural health product for digestive health
• Supportive therapy for irritable bowel syndrome

Approved in Japan as Probiotics for:

• Food for specified health uses (FOSHU) for gut health
• Prevention of allergic diseases

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

University of Miami

Collaborator

Trials

976

Recruited

423,000+

University of Louisville

Collaborator

Trials

353

Recruited

76,400+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Exegi Pharma, LLC

Industry Sponsor

Trials

3

Recruited

220+

Soterix Medical

Industry Sponsor

Trials

12

Recruited

410+

Exegi Pharma, LLC

Collaborator

Trials

2

Recruited

170+

Published Research Related to This Trial

A meta-analysis of 7 human trials and 11 animal studies found that probiotics significantly enhance cognitive function, with a moderate effect size of 0.24 in humans and a strong effect size of 0.90 in animals.

Probiotics were particularly effective in cognitively impaired individuals compared to healthy individuals, suggesting that tailored probiotic interventions may be beneficial for those with cognitive disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotics treatment improves cognitive impairment in patients and animals: A systematic review and meta-analysis. Lv, T., Ye, M., Luo, F., et al.[2021]

Ingestion of the probiotic Lactobacillus rhamnosus (JB-1) significantly increased neuronal activity in the mesenteric nerve bundle of mice, indicating that it influences gut-brain signaling through vagal afferents.

The effects of JB-1 on neuronal firing were completely blocked by prior vagotomy, suggesting that the gut-brain communication facilitated by this probiotic is dependent on the vagus nerve, highlighting its potential role in psychiatric treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents. Perez-Burgos, A., Wang, B., Mao, YK., et al.[2022]

A 3-week intake of probiotics significantly improved body composition in normal weight obese (NWO) and preobese-obese (PreOB/OB) women, leading to reductions in BMI and fat mass, and increases in fat-free mass.

Probiotic treatment also resulted in lower psychological distress and improved gut health, as indicated by reduced symptoms of bacterial overgrowth and better orocecal transit time, suggesting a beneficial effect on both physical and mental health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can psychobiotics intake modulate psychological profile and body composition of women affected by normal weight obese syndrome and obesity? A double blind randomized clinical trial. De Lorenzo, A., Costacurta, M., Merra, G., et al.[2018]

In a study involving 22 healthy participants, a probiotic mixture was found to alter brain activity and functional connectivity during emotional tasks, suggesting that probiotics can influence brain function beyond changes in gut microbiota composition.

The probiotic intervention led to increased activation in the orbitofrontal cortex, a key area for emotional processing, indicating potential mechanisms through which probiotics may affect emotional regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses Toward an Emotional Task in Healthy Subjects: A Randomized Clinical Trial. Rode, J., Edebol Carlman, HMT., König, J., et al.[2022]

In a study involving 22 healthy participants, a probiotic blend significantly reduced brain activation in areas associated with stress processing, suggesting it may help manage stress responses.

The probiotics did not change salivary cortisol levels or cognitive performance, indicating that while they can subtly influence brain activity related to stress, they may not affect all physiological stress markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses to an Arithmetic Stress Task in Healthy Subjects: A Randomised Clinical Trial and Proof-of-Concept Study. Edebol Carlman, HMT., Rode, J., König, J., et al.[2022]

Probiotic treatment with Lactobacillus rhamnosus and Bifidobacterium animalis significantly increased the excitability of hippocampal CA1 pyramidal neurons in male germ-free mice, indicating a direct effect on neuronal activity.

The effects of probiotics on neuronal excitability were reversed when the gut microbiome was reintroduced, highlighting the importance of gut microbiota status in mediating the neuronal effects of probiotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Homeostatic regulation of neuronal excitability by probiotics in male germ-free mice. Kim, J., Kim, DW., Lee, A., et al.[2022]

In a study using Swiss albino mice, oral Ampicillin caused gut dysbiosis, leading to cognitive decline and neuronal damage, as indicated by reduced levels of beneficial gut bacteria and increased oxidative stress.

Probiotic treatment alongside the antibiotic partially reversed the negative effects on cognition and protected hippocampal neurons from inflammation and oxidative damage, suggesting a neuroprotective role of probiotics against gut-related cognitive impairments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotics protect against gut dysbiosis associated decline in learning and memory. Roy Sarkar, S., Mitra Mazumder, P., Banerjee, S.[2020]

Citations

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

Probiotics treatment improves cognitive impairment in patients and animals: A systematic review and meta-analysis. [2021]

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

Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Can psychobiotics intake modulate psychological profile and body composition of women affected by normal weight obese syndrome and obesity? A double blind randomized clinical trial. [2018]

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

Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses Toward an Emotional Task in Healthy Subjects: A Randomized Clinical Trial. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses to an Arithmetic Stress Task in Healthy Subjects: A Randomised Clinical Trial and Proof-of-Concept Study. [2022]

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

Homeostatic regulation of neuronal excitability by probiotics in male germ-free mice. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Probiotics protect against gut dysbiosis associated decline in learning and memory. [2020]