Synbiotic Therapy for NP-PASC

Pilot Study of Synbiotic Therapy for Neuropsychiatric PASC

Gut microbiome dysbiosis has been noted in patients with Post-acute sequelae (PASC) of Severe Acute Respiratory Syndrome-CoronaVirus -2 (SARS-CoV-2). A study performed at Columbia found that plasma levels of the short chain fatty acid (SCFA), butyric acid, remained lower in people with Neuropsychiatric PASC (NP-PASC) than in people with PASC after SAR-CoV-2 infection. 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 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 NP-PASC. The intervention will be a mixture of the prebiotic resistant starch and the probiotic Bifidobacterium adolescentis in-vivo selection 1 strain (iVS-1). The placebo will be Maltodextrin.

Study Overview

• Status: Completed
• Conditions: Long COVID-19; Post-Acute COVID-19 Syndrome
• Intervention / Treatment: Dietary supplement: Synbiotic IVS-1; Dietary supplement: Maltodextrin

Detailed Description

In this pilot study, up to 30 participants with NP-PASC at Columbia University Medical Center (CUIMC) will be randomized to take the intervention (n=15) or placebo (n=15). Both intervention and placebo will be similar in terms of appearance and taste, and participants will be asked to take the intervention or placebo with water twice daily, for up to 4 weeks. At the enrollment and study follow-up visit, the investigators will obtain data on acceptability and feasibility, including feasibility of assessing adherence and outcomes, and collect blood, rectal swabs and stool for outcome assessment.

The study intervention is a mixture of the prebiotic potato RS (Bobs Red Mill) and the probiotic IVS-1 (Bifidobacterium adolescentis). One dose will be RS and IVS-1 mixed together in a single-use sachet. The placebo will be Maltodextrin, a carbohydrate, packaged similarly to the intervention. Participants will take one dose twice daily with water, for 4 weeks. Each participant will receive a 4-week supply of sachets at the screening/enrollment visit.

There will be a total of two visits: screening/enrollment/randomization and week 4. During the screening visit, study information will be provided to potential participants, and interested participants will sign an informed consent and undergo screening procedures. Those who meet eligibility criteria will then undergo enrollment and randomization procedures on the same day. Data on sociodemographic and medical history will be collected using surveys, and relevant samples will also be collected at the first visit as well as a self-administered rectal swab, and self-collected stool for gut microbiome studies and blood test for SCFA levels. The participant will then initiate the intervention or placebo, and the study staff will counsel and support the participants on administration of the intervention or placebo. At the 4-week visit, clinical data and samples will be collected, as well as data on acceptability, feasibility, adherence.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. >18 years of age,
2. Prior mild acute SARS-CoV-2 infection (positive testing by FDA approved antigen or molecular test or positive anti-nucleocapsid antibody) and not requiring hospitalization
3. Meeting Center for Disease Control (CDC) criteria for PASC (any new or recurrent symptom present >4 weeks after SARS-COV-2 infection)
4. Meeting 2015 Institute of Medicine (IOM) criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME-CFS) of 3 required symptoms for fatigue to select for individuals specifically with NP-PASC (a substantial reduction or impairment in ability to engage in pre-illness levels of activity, post-exertional malaise, and unrefreshing sleep) and at least one of the two following manifestations (cognitive impairment or orthostatic intolerance).
5. meets cognitive impairment threshold on neurocognitive battery.

Exclusion Criteria:

1. Pregnancy or breastfeeding

2. Currently taking or using the following non-study products within 30 days prior to study entry:

   • probiotics, prebiotics, or fiber supplements
   • immunosuppressive or immunomodulatory drugs
   • antibiotics
3. Heavy drug or alcohol use
4. Known allergy to any of the study products
5. Serious illness requiring systemic treatment and/or hospitalization within 30 prior to study entry
6. Liver cirrhosis, history of inflammatory bowel disease, or other major conditions related to colon
7. Any episode of acute or persistent diarrhea within 1 day prior to study entry

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Synbiotic Therapy; A mixture of the prebiotic potato resistant starch (RS, Bobs Red Mill) and the probiotic IVS-1 (Bifidobacterium adolescentis).	Dietary supplement: Synbiotic IVS-1; A mixture of the prebiotic potato resistant starch (RS, Bobs Red Mill) and the probiotic IVS-1 (Bifidobacterium adolescentis).; Other Names: Prebiotic+Probiotic
Placebo Comparator: Placebo; The placebo to be used is Maltodextrin, a carbohydrate packaged similarly to the study intervention.	Dietary supplement: Maltodextrin; Maltodextrin, a carbohydrate packaged similarly to the study intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in plasma short chain fatty acid (SCFA) levels between study arms	SCFA levels will be measured from plasma samples and compared between the intervention group and the placebo group. In-group differences will also be measured between baseline and 4 weeks.	4 weeks
Difference in gut microbiota between study arms	Bacterial flora will be measured from rectal swab samples and compared between the intervention group and the placebo group. In-group differences will also be measured between baseline and 4 weeks.	4 weeks
Difference in other biomarkers between study arms	Additional biomarkers, such as serotonin and inflammatory cytokines, measured from the plasma samples and rectal swabs, whose concentration will be compared between the intervention group and the placebo group, and in-group differences between timepoints. Additional biomarkers include, but are not limited to, inflammatory cytokines and serotonin.	4 weeks
Difference in clinical profiles between study arms	Survey data will be compared between the intervention group and the placebo group, and in-group differences between timepoints. Survey data includes, but is not limited to, medication, COVID History, Vaccine History, and Medical History.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants enrolled per week and agree to take the intervention	This measures the feasibility and acceptability of the study drug.	4 weeks
Number of participants who successfully take the intervention	This measures the feasibility and acceptability of the study drug.	4 weeks
Difference in NP-PASC symptoms between study arms	NP-PASC symptom severity differences as assessed by the NeuroScreen app between the baseline and the 4 week timepoint, and differences between the intervention and the placebo group.	4 weeks

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Principal Investigator: Michael Yin, MD, MS, Columbia University; Principal Investigator: Rupak Shivakoti, PhD, MHS, Columbia Universtiy Medical Center

Publications and helpful links

General Publications

• Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; Board on the Health of Select Populations; Institute of Medicine. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Washington (DC): National Academies Press (US); 2015 Feb 10. Available from http://www.ncbi.nlm.nih.gov/books/NBK274235/
• Liu Q, Mak JWY, Su Q, Yeoh YK, Lui GC, Ng SSS, Zhang F, Li AYL, Lu W, Hui DS, Chan PK, Chan FKL, Ng SC. Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome. Gut. 2022 Mar;71(3):544-552. doi: 10.1136/gutjnl-2021-325989. Epub 2022 Jan 26.
• Pandey KR, Naik SR, Vakil BV. Probiotics, prebiotics and synbiotics- a review. J Food Sci Technol. 2015 Dec;52(12):7577-87. doi: 10.1007/s13197-015-1921-1. Epub 2015 Jul 22.
• Kearney SM, Gibbons SM, Erdman SE, Alm EJ. Orthogonal Dietary Niche Enables Reversible Engraftment of a Gut Bacterial Commensal. Cell Rep. 2018 Aug 14;24(7):1842-1851. doi: 10.1016/j.celrep.2018.07.032.
• Maldonado-Gomez MX, Martinez I, Bottacini F, O'Callaghan A, Ventura M, van Sinderen D, Hillmann B, Vangay P, Knights D, Hutkins RW, Walter J. Stable Engraftment of Bifidobacterium longum AH1206 in the Human Gut Depends on Individualized Features of the Resident Microbiome. Cell Host Microbe. 2016 Oct 12;20(4):515-526. doi: 10.1016/j.chom.2016.09.001. Epub 2016 Sep 29.
• Sonnenburg ED, Smits SA, Tikhonov M, Higginbottom SK, Wingreen NS, Sonnenburg JL. Diet-induced extinctions in the gut microbiota compound over generations. Nature. 2016 Jan 14;529(7585):212-5. doi: 10.1038/nature16504.
• Grooms KN, Ommerborn MJ, Pham DQ, Djousse L, Clark CR. Dietary fiber intake and cardiometabolic risks among US adults, NHANES 1999-2010. Am J Med. 2013 Dec;126(12):1059-67.e1-4. doi: 10.1016/j.amjmed.2013.07.023. Epub 2013 Oct 15.

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2024
• Primary Completion (Actual): August 6, 2025
• Study Completion (Actual): August 6, 2025

Study Registration Dates

• First Submitted: September 26, 2024
• First Submitted That Met QC Criteria: September 27, 2024
• First Posted (Actual): October 1, 2024

Study Record Updates

• Last Update Posted (Estimated): August 26, 2025
• Last Update Submitted That Met QC Criteria: August 25, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Post-Infectious Disorders; COVID-19; Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Pathological Conditions, Signs and Symptoms; Post-Acute COVID-19 Syndrome; maltodextrin
• Other Study ID Numbers: AAAV3630

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Participant confidentiality will be maintained and individual participant data will not be provided to other researchers, and there is no plan to do so.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No