Synbiotic Therapy for Long COVID Syndrome

Overseen By Jayesh Shah

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Columbia University

Must not be taking: Probiotics, Prebiotics, Antibiotics, others

Disqualifiers: Pregnancy, Heavy drug use, Liver cirrhosis, others

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with ongoing symptoms after a mild COVID infection, known as Long COVID. The goal is to determine if a special combination of probiotics and prebiotics (healthful bacteria and fibers), called Synbiotic IVS-1, can improve gut health and reduce symptoms such as brain fog and fatigue. Participants will receive either this synbiotic mix or a placebo (a harmless substance resembling the treatment). Ideal candidates for the trial are those who have experienced Long COVID symptoms like fatigue and brain fog for more than four weeks and have not recently used probiotics or taken certain medications. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research on Long COVID.

Will I have to stop taking my current medications?

The trial requires that you stop taking probiotics, prebiotics, fiber supplements, immunosuppressive or immunomodulatory drugs, and antibiotics at least 30 days before joining the study.

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

Research has shown that synbiotics, a mix of prebiotics and probiotics, are generally well-tolerated. Studies have found these mixtures can improve gut health without major side effects. A similar synbiotic mix was tested in Hong Kong for individuals with post-acute COVID-19 syndrome, and no significant negative effects were reported, suggesting its safety.

The synbiotic treatment under investigation includes resistant starch, a type of fiber, and Bifidobacterium adolescentis, a bacterial strain. Both are considered safe for most people. Although this specific combination hasn't been extensively studied in the U.S. for long COVID, synbiotics generally have a strong safety record. Prospective trial participants can feel confident that the treatment is expected to be well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike other treatments for Long COVID that often involve symptom management through medications like steroids, antihistamines, or antidepressants, Synbiotic IVS-1 offers a novel approach by targeting gut health. This treatment combines a prebiotic, potato resistant starch, and a probiotic, Bifidobacterium adolescentis, to potentially rebalance the gut microbiome, which researchers believe could play a role in alleviating Long COVID symptoms. This synbiotic therapy could address underlying causes rather than just symptoms, opening up a new avenue for effective treatment. Researchers are excited because this approach could improve overall health and immunity, providing a holistic benefit beyond what's currently available.

What evidence suggests that synbiotic therapy might be an effective treatment for Long COVID?

This trial will evaluate the effectiveness of Synbiotic IVS-1 for long COVID syndrome. Research has shown that synbiotics, like the one tested in this trial, can aid recovery from long COVID by improving gut health. In earlier studies, a synbiotic formula called SIM01 boosted antibody levels in COVID-19 patients. Synbiotics are known to increase short-chain fatty acids (SCFAs), crucial for gut health and often lower in people with long COVID. A synbiotic combines a prebiotic (food for good bacteria) and a probiotic (good bacteria), improving gut balance and potentially easing long COVID symptoms. Early signs suggest this method might help manage symptoms by enhancing gut function and the immune system. ^{1 2 4 5 6}

Who Is on the Research Team?

Michael Yin, MD, MS

Principal Investigator

Columbia University

Rupak Shivakoti, PhD, MHS

Principal Investigator

Columbia Universtiy Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals experiencing long-term symptoms after COVID-19, known as Post-COVID Syndrome or Long COVID. Participants should have neuropsychiatric symptoms and will be assessed to ensure their condition aligns with the study's focus on gut health related to post-COVID recovery.

Inclusion Criteria

I experience severe fatigue, unrefreshing sleep, and worsen after physical or mental activity.

I am older than 18 years.

I have long-term symptoms from COVID-19 lasting more than 4 weeks.

Exclusion Criteria

Pregnancy or breastfeeding

Heavy drug or alcohol use

Known allergy to any of the study products

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants receive either the synbiotic therapy or placebo for 4 weeks

4 weeks

1 visit (in-person) at week 4

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Synbiotic IVS-1

Trial Overview The trial is testing Synbiotic IVS-1—a combination of a prebiotic (resistant starch) and a probiotic (Bifidobacterium adolescentis strain iVS-1)—against Maltodextrin, which serves as a placebo. The goal is to see if Synbiotic IVS-1 can improve gut health by increasing beneficial fatty acids in people with Long COVID.

How Is the Trial Designed?

Group I: Synbiotic Therapy Experimental Treatment 1 Intervention

A mixture of the prebiotic potato resistant starch (RS, Bobs Red Mill) and the probiotic IVS-1 (Bifidobacterium adolescentis).

Group II: Placebo Placebo Group 1 Intervention

The placebo to be used is Maltodextrin, a carbohydrate packaged similarly to the study intervention.

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Published Research Related to This Trial

In a randomized, double-blind, placebo-controlled trial involving 463 patients with post-acute COVID-19 syndrome (PACS), the synbiotic preparation SIM01 significantly alleviated symptoms such as fatigue, memory loss, and difficulty in concentration after 6 months of treatment.

The safety profile of SIM01 was comparable to placebo, with similar rates of adverse events, suggesting it is a safe option for managing PACS symptoms through modulation of the gut microbiome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial. Lau, RI., Su, Q., Lau, ISF., et al.[2023]

A study involving 200 hospitalized COVID-19 patients found that a multi-strain probiotic did not significantly affect overall mortality or major health outcomes, such as the need for intensive care or mechanical ventilation.

However, the probiotic was effective in reducing the duration of diarrhea associated with COVID-19 and preventing hospital-acquired diarrhea in patients receiving a single antibiotic, indicating its potential benefit in managing gastrointestinal symptoms during COVID-19 treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of a Probiotic Consisting of Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301 in the Treatment of Hospitalized Patients with COVID-19: a Randomized Controlled Trial. Ivashkin, V., Fomin, V., Moiseev, S., et al.[2023]

A 2-month nutritional intervention using a high-fiber formula significantly alleviated gastrointestinal symptoms in a patient with post-acute COVID-19 syndrome, leading to improvements in appetite, anxiety, and medication dosage for nausea.

The intervention resulted in beneficial changes in the patient's gut microbiota, including the increase of short-chain fatty acid-producing bacteria, which may be linked to symptom relief, highlighting the potential of gut microbiota modulation as a therapeutic strategy for post-COVID-19 gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional Modulation of Gut Microbiota Alleviates Severe Gastrointestinal Symptoms in a Patient with Post-Acute COVID-19 Syndrome. Wang, Y., Wu, G., Zhao, L., et al.[2022]

In a study of 44 moderate/severe COVID-19 inpatients, those who received an oral booster of single-strain probiotic bifidobacteria had a significantly shorter hospital stay (median of 7.6 days) compared to those who did not receive the probiotic.

The probiotic group also showed improved clinical outcomes, including better radiological improvement and lower levels of interleukin-6, with a mortality rate of 5% compared to 25% in the non-probiotic group, suggesting that probiotics may enhance recovery in severe COVID-19 cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral booster probiotic bifidobacteria in SARS-COV-2 patients. Bozkurt, HS., Bilen, Ö.[2022]

In a study involving 25 hospitalized COVID-19 patients, the synbiotic formula SIM01 significantly improved antibody response against SARS-CoV-2, with 88% of patients developing IgG antibodies compared to 63.3% in the control group by Day 16.

Patients receiving SIM01 also showed reduced levels of pro-inflammatory markers and a significant decrease in nasopharyngeal viral load, indicating that this synbiotic may help restore gut health and improve immune responses in COVID-19 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gut microbiota-derived synbiotic formula (SIM01) as a novel adjuvant therapy for COVID-19: An open-label pilot study. Zhang, L., Xu, Z., Mak, JWY., et al.[2022]

Healthy gut microbiota plays a crucial role in reducing the severity of COVID-19, and gut dysbiosis is linked to worse outcomes in infected individuals.

There are currently 19 clinical trials investigating the use of probiotics and synbiotics to prevent and treat COVID-19, highlighting the potential of gut microbiota modulation as a therapeutic strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of Gut Microbiota for the Prevention and Treatment of COVID-19. Chen, J., Vitetta, L.[2021]

In a randomized placebo-controlled trial involving 78 hospitalized COVID-19 patients, synbiotic supplementation significantly reduced serum levels of the pro-inflammatory marker interleukin-6 (IL-6) after 2 weeks, suggesting its potential to modulate inflammatory responses during COVID-19 infection.

The synbiotic group also showed a significant increase in white blood cell (WBC) counts from pre to post-treatment, indicating an immune response, although other inflammatory markers like C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) did not show significant differences compared to the placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of synbiotic adjunct therapy on clinical and paraclinical outcomes in hospitalized COVID-19 patients: A randomized placebo-controlled trial. Vaezi, M., Ravanshad, S., Akbari Rad, M., et al.[2023]

In a study of 100 adult patients with moderate pneumonia caused by SARS-CoV-2, the use of sorbed Bifidobacterium bifidum 1 significantly improved symptoms such as weakness, hypoosmia/dysgeusia, and cough, reducing their duration and frequency compared to standard treatment.

The probiotic also lowered the risk of antibiotic-associated diarrhea by 20% and did not show any side effects, indicating a high safety profile while enhancing patient well-being during recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficiency of application of sorbed probiotics in complex therapy of pneumonia caused by SARS-CoV-2. Part 1. Heating clinical displays period]. Meskina, ER., Tselipanova, EE., Khadisova, MK., et al.[2022]

Citations

1. thelancet.com thelancet.com/journals/laninf/article/piis1473-3099(23)00685-0/fulltext

A synbiotic preparation (SIM01) for post-acute COVID-19 ... Treatment with SIM01 alleviates multiple symptoms of PACS. Our findings have implications on the management of PACS through gut microbiome ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06620406?cond=Post-Acute%20COVID19%20Syndrome&limit=100&aggFilters=status:rec&rank=25

NCT06620406 | Synbiotic Therapy for NP-PASC The purpose of this pilot study is to characterize changes in plasma SCFA levels and gut microbiome after treatment with synbiotics and placebo in people with ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12375777/

The resident gut microbiome modulates the effect of synbiotics ... The study aims to tackle the seed and soil microbiome and mechanisms that contribute to the effect of synbiotics in enhancing immunogenicity ...

4. withpower.com withpower.com/trial/phase-post-acute-covid-19-syndrome-8-2024-47c32

Synbiotic Therapy for Long COVID Syndrome In a study involving 25 hospitalized COVID-19 patients, the synbiotic formula SIM01 significantly improved antibody response against SARS-CoV-2, with 88% of ...

5. ctv.veeva.com ctv.veeva.com/study/synbiotic-therapy-for-np-pasc

Synbiotic Therapy for NP-PASC - ClinicalTrials.Veeva Synbiotics improve SCFA levels and are well-tolerated in the general population but have not been studied among people with PASC in the United States. The ...

6. reaganudall.org reaganudall.org/clinical-trial/synbiotic-therapy-np-pasc

Synbiotic Therapy for NP-PASC Gut microbiome dysbiosis has been noted in patients with Post-acute sequelae (PASC) ofSevere Acute Respiratory Syndrome-CoronaVirus -2 (SARS-CoV-2).