Evaluating the Effects of a Fermented Diet on Microbiome Diversity in Individuals With Long COVID

NCT ID: NCT06560554

Last Updated: 2025-12-03

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-05
• Study Completion Date: 2026-04-30

Brief Summary

The purpose of this study is to evaluate the effects of fermented foods on bacterial gut microbiome diversity of long-COVID subjects.

Detailed Description

This will be a single-center, longitudinal randomized controlled trial assessing a high fermented food diet intervention among patients with long COVID.

The investigators will adapt the high fermented food diet intervention previously described by Wastyk et al to our population of patients with long COVID. A list of people meeting inclusion criteria who are open to research participation will be generated by the study team members working in the long COVID clinic; eligible patients will be contacted by a different member of the study team (not working in the long COVID clinic).

Participants who agree to take part in the study will be randomized using REDCap into one of two arms, a control arm (no diet intervention), or an intervention arm. 20 participants will be assigned to each group (40 total). The study will consist of 2 in-person visits at baseline and week 13. There will be weekly phone calls during weeks 1 through 12 for participants on the intervention arm; participants in the control arm will be contacted as needed to ensure that they continue to document their diet three days a week.

All participants will provide a total of two stool samples (baseline and week 13), and undergo psychometric evaluation with Hospital Anxiety and Depression Scale (HADS) A/D, Impact of Event Scale - revised (IES-R), Montreal Cognitive Assessment (MoCA)-blind and European Quality of Life 5 Dimensions 5 Level Version (EuroQol-5D-5L) (baseline and week 13). Demographic information on the subjects will also be collected (age, gender, past medical history including mental health diagnoses or cognitive diagnoses, time of COVID infection, etc).

During the baseline visit, the investigators will interview all study participants and ask participants to provide details about their diet and any use of probiotic foods or supplements. All participants will install the food tracking application, Mayo Clinic Diet App, on their personal smart device and will receive instructions on how to use it by a study team member. An account for each participant will be set up by the study team and participants will be given a username and password. The investigators will have access to the data entered. Participants will be instructed to document their food intake at least three days every week, two weekdays and one weekend day as was done in the study by Wastyk et al. After the study, participants may change their password if they would like to continue food tracking.

Intervention Group:

Participants assigned to the intervention arm will receive an in-person teaching session delivered by a trained team member. The session will include introductory education on microbiome and a description on a variety of probiotic fermented foods commercially available (fermented dairy products, fermented vegetables, fermented non-alcoholic drinks). Participants will be able to choose their own probiotic fermented foods based on this education and taste preference.

After the visit, intervention arm participants will begin to incorporate probiotic fermented foods into their diet during weeks 1-4 of the study (ramp up phase). Participants will start with one serving of fermented food of their choice a day, increasing to 6+/day as tolerated by the end of week 4. Weeks 5-12 will serve as the intervention maintenance phase, with the target of a daily intake of 6+ servings per day of fermented foods.

Fermented food intake will be reported as the average number of servings per day for each week of the intervention. One serving of probiotic fermented foods will be defined as: kombucha, yogurt, kefir, buttermilk, kvass, other probiotic fermented liquids = 6 oz, kimchi, sauerkraut, other probiotic fermented veggies = 1/4 cup, vegetable brine drink/gut shot from approved list = 2 oz.

Food logs will be reviewed by the investigators to assess compliance and provide recommendations to increase amounts or variety of fermented foods in the diet as tolerated. Investigators will interact weekly with participants in the intervention arm by phone or zoom to review probiotic fermented food intake, answer questions, inquire about any gastrointestinal symptoms such as bloating or upset stomach, and provide motivation to continue with the diet. Study participants in the intervention arm will also be asked to assess their overall compliance with the diet on a scale of 0-10, with zero being "not at all" and 10 being "exactly as recommended [during the specific phase of the study]".

Control Group:

The participants in the control arm will only complete the baseline and week 13 visits. Participants in the control arm will be contacted as needed to ensure that they document their regular food intake 3 days a week. Control group participants will not be asked to make any changes to their diet, only to document their regular diet 3 days a week.

At approximately 13 weeks, all participants will collect and return a stool sample and repeat the study questionnaires. Participants will be able to complete the questionnaires in person, virtually, or by phone.

Conditions

Long COVID

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Control

The subjects in the control arm will only complete the baseline and week 13 visits. They will not be asked to make any changes to their diet, only to document their regular diet 3 days a week.

Group Type: ACTIVE_COMPARATOR

Control

Intervention Type: OTHER

No information on incorporation of fermented foods will be provided for subjects in the control arm.

Treatment

Will receive an in-person teaching session delivered by a trained team member including introductory education on microbiome and a description on a variety of probiotic fermented foods commercially available (fermented dairy products, fermented vegetables, fermented non-alcoholic drinks). Participants will be able to choose their own probiotic fermented foods based on this education and taste preference. Subjects will be contacted weekly to ensure they are tolerating and adhering to the study protocol.

Group Type: EXPERIMENTAL

Fermented foods

Intervention Type: OTHER

Participants randomized to the intervention arm will begin to incorporate probiotic fermented foods into their diet during weeks 1-4 of the study (ramp up phase). They will start with one serving of fermented food of their choice a day, increasing to 6+/day as tolerated by the end of week 4. Weeks 5-12 will serve as the intervention maintenance phase, with the target of a daily intake of 6+ servings of fermented foods.

Interventions

Fermented foods

Participants randomized to the intervention arm will begin to incorporate probiotic fermented foods into their diet during weeks 1-4 of the study (ramp up phase). They will start with one serving of fermented food of their choice a day, increasing to 6+/day as tolerated by the end of week 4. Weeks 5-12 will serve as the intervention maintenance phase, with the target of a daily intake of 6+ servings of fermented foods.

Intervention Type: OTHER

Control

No information on incorporation of fermented foods will be provided for subjects in the control arm.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Adult (> 18 years old)

2. Patients who have long COVID symptoms

a. Long COVID will be defined as: i. A previously documented COVID + infection within the last year ii. A presence of neurological symptoms that started within 4 weeks of the COVID infection (fatigue, difficulty concentrating, depression, anxiety) as per CDC definition of Long Covid.

3. Own a smart device capable of downloading a food logging application. Able to understand and document informed consent

4. Seen in the Mayo Clinic long-COVID Clinic within the Department of General Internal Medicine

Exclusion Criteria

1. History of dementia, moderate or severe cognitive dysfunction, developmental delay, psychotic disorders such as schizophrenia

2. Unable to tolerate oral foods

3. Potential contraindications to a fermented food diet (chronically immunosuppressed including organ transplant recipients)

4. Neutropenic as listed in the "active problems" list in the EMR

5. Undergoing chemotherapy at the time of consent

6. Taking MAOIs at the time of consent.

7. Active uncontrolled inflammatory bowel disease including ulcerative colitis, Crohn's disease, indeterminate colitis, irritable bowel syndrome (moderate or severe), infectious gastroenteritis, colitis or gastritis, Clostridium difficile infection (recurrent), malabsorptive diseases (such as Celiac disease), major surgery of the GI tract with the exception of cholecystectomy and/or appendectomy in the past 5 years, or any major bowel resection at any time.

8. A reported consumption of 2 servings of probiotic fermented food per day in their normal baseline diet.

9. Pregnancy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Lioudmila Karnatovskaia

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Liousmila V Karnatovskaia, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

References

Wastyk HC, Fragiadakis GK, Perelman D, Dahan D, Merrill BD, Yu FB, Topf M, Gonzalez CG, Van Treuren W, Han S, Robinson JL, Elias JE, Sonnenburg ED, Gardner CD, Sonnenburg JL. Gut-microbiota-targeted diets modulate human immune status. Cell. 2021 Aug 5;184(16):4137-4153.e14. doi: 10.1016/j.cell.2021.06.019. Epub 2021 Jul 12.

Reference Type: BACKGROUND

PMID: 34256014 (View on PubMed)

Other Identifiers

24-005170

Identifier Type: -

Identifier Source: org_study_id