Synbiotic Therapy for NP-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.

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.

Eligibility Criteria:
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