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 trial aims to explore how two different treatments can improve brain function. One treatment uses a device called tVNS to stimulate a nerve, potentially reducing inflammation and boosting cognition. The other involves taking a probiotic supplement (live biotherapeutic product) to balance gut bacteria, particularly for those with HIV who consume alcohol. This trial suits individuals aged 35-70 who speak English or Spanish, drink alcohol, and experience some cognitive difficulties. As an unphased trial, it offers a unique opportunity to contribute to groundbreaking research and potentially benefit from innovative treatments.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that probiotics are generally safe, with rare side effects that usually resolve on their own. Probiotics improve gut health and may also enhance brain function in older adults.

Studies on transcutaneous vagal nerve stimulation (tVNS) indicate it is safe, with mostly mild and short-term side effects. As a non-invasive method, it does not involve surgery. Most people tolerate it well, making it a promising option for improving brain health.

Both treatments have demonstrated good safety records in previous research, suggesting they could be safe options for those considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine two innovative approaches to potentially boost cognitive function. Unlike typical medications or therapies, the probiotic supplement Visbiome introduces beneficial bacteria to support gut health, which may have a positive impact on brain function through the gut-brain axis. Meanwhile, Transcutaneous Vagal Nerve Stimulation (tVNS) uses a non-invasive device to stimulate the vagus nerve, which is thought to enhance brain activity and improve cognition. This combination of gut microbiome support and nerve stimulation offers a fresh, holistic approach that stands apart from traditional cognitive treatments.

What evidence suggests that this trial's treatments could be effective for cognition improvement?

Research has shown that probiotics can greatly improve brain function. A recent study found that a specific probiotic supplement helped mice remember better and reduced brain inflammation. Another review of studies found that probiotics helped people with memory problems think more clearly. In this trial, some participants will receive a probiotic supplement to evaluate its effects on cognition.

Transcutaneous Vagal Nerve Stimulation (tVNS) also shows promise for boosting brain power. Research suggests that tVNS can improve memory, especially verbal memory, and help people process information faster. Other participants in this trial will receive tVNS to assess its impact on cognitive enhancement. Both treatments focus on the connection between the gut and the brain and may enhance thinking skills. ^{1 4 6 7 8}

Who Is on the Research Team?

Robert L Cook, MD

Principal Investigator

University of Florida

Eric Porges, PhD

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

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9548122/

Recent developments in the probiotics as live biotherapeutic ... Randomized clinical trial examining the impact of Lactobacillus rhamnosus GG probiotic supplementation on cognitive functioning in middle-aged ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36629438/

Probiotic supplements are effective in people with cognitive ... According to this meta-analysis, probiotic supplementation had a highly significant effect on cognitive function in people with cognitive impairment or ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2950194625002651

The role of probiotics in personalized therapeutics Emerging evidence supports the role of personalized probiotics in managing conditions like inflammatory bowel diseases and metabolic syndromes by correcting ...

4. imrpress.com imrpress.com/journal/JIN/22/4/10.31083/j.jin2204092/htm

Probiotics Improve Cognitive Impairment by Decreasing ... Results: ProBiotic-4-treated SAMP8 mice showed improvement in memory deficits, synaptic and cerebral neuronal injuries, and microglial ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2772753X25000358

A review on probiotics and dietary bioactives This review explores the impact of probiotics and dietary bioactives on gut microbiota, inflammatory responses, and metabolic well-being.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7319051/

Live Biotherapeutic Products, A Road Map for Safety ... This section propose a risk analysis generally applicable to all LBPs, taking into account the microorganisms themselves and the characteristics ...

7. eurjmedres.biomedcentral.com eurjmedres.biomedcentral.com/articles/10.1186/s40001-021-00509-7

Factors that influence clinical efficacy of live biotherapeutic ... While probiotics are generally considered safe and adverse events of probiotics are rare and almost always reversible, the problem may arise ...

8. jocmr.org jocmr.org/index.php/JOCMR/article/view/4575/25893467

Microbial Therapeutics in Neurocognitive and Psychiatric ... It was also found that probiotic and selenium co-supplementation resulted in a significant improvement in cognition over a 12-week period in AD ...