PROVID-LD: WHO COVID-19 - Evaluation of the Efficacy of Probiotics to Reduce the Occurrence of Long COVID

Sponsor

Centre de recherche du Centre hospitalier universitaire de Sherbrooke (Other)

Overall Status

Recruiting

CT.gov ID

NCT05080244

Collaborator

Lallemand Health Solutions (Industry)

618

Enrollment

Location

Arms

9.1

Anticipated Duration (Months)

67.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Probiotics may be considered as an option of treatment for long COVID since they have anti-viral effect, trigger immunomodulation and have low side-effects. This randomized controlled trial aims to reduce the number of patients with long COVID by 25% 90 days after the COVID-19 diagnosis by taking probiotics in a symptomatic population, self-caring at home. During the acute phase of the disease, participants will take two capsules (probiotics or placebo) per day for 10 days and one capsule (probiotics or placebo) per day for the following 15 days. A follow-up will be done twice during the acute phase, 14 days and 28 days after starting to take the investigational product (compliance to treatment, side effects, etc.). At inclusion and at Day14, Day30 and Day90 after the COVID-19 diagnosis, a questionnaire will be administered (COVID-19 symptoms, anxiety, functioning difficulties, etc.) and 2 saliva and 2 stool (viral and microbiota analyzes) self-samples will be performed.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Dietary Supplement: Probiotics Dietary Supplement: Placebo	N/A

Detailed Description

Rational:

COVID-19 disease caused by a new coronavirus (SARS-CoV-2) has received worldwide attention. No effective treatment against COVID-19 is available and the current vaccination appears essential to control the pandemic. However, many questions remain, such as the durability of immunity and the appearance of variants. While the acute phase has been widely studied, the long-term consequences are unknown, and a new burden is emerging: the long COVID. The long COVID is defined by the persistence of symptoms of the disease for more than 4 weeks after diagnosis. Several strong arguments support the study of probiotics for COVID-19: 1) probiotics act on viruses by various well described mechanisms (reduction of absorption, cellular internalization of the virus, production of metabolites/substances having a direct antiviral effect and immunomodulation); 2) probiotics are considered with a high level of evidence (meta-analysis) to reduce diarrhea (associated with antibiotics and Clostridium difficile) and for respiratory tract infections and 3) probiotics are affordable and available with low side-effects.

Objectives:

Primary objective: Reduce the number of patients with long COVID by 25% 90 days after the COVID-19 diagnosis by taking probiotics during the acute phase of the disease.

Secondary objectives (SO).

SO1: Reduce the number of patients with long COVID by 25% 30 days after the COVID-19 diagnosis by taking probiotics during the acute phase of the disease.

SO2: Improve the understanding of the mechanism of action of probiotics on long COVID from salivary and fecal virological and microbiota analyzes.

SO3: Identify the prognostic factors measured at the baseline (inclusion) associated with long COVID (socio-demographic, clinical, virological, microbiological factors) and the time-dependent factors after the baseline.

Population:

618 men and women, 18 years or older, with a first positive test for COVID-19 in the last 10 days, having symptoms of the COVID-19, self-caring at home, living in Quebec for the next 90 days, able to take medication alone, with access to a phone or to the Internet.

Randomization:

Patients will be randomized in one of the study groups (stratified by age and gender). The randomization is double-blinded and uses a ratio 1:1. Group A: will take probiotics for 25 days / Group B: will take placebo for 25 days.

Intervention:

During the acute phase of the disease, participants will take two capsules (probiotics or placebo) per day (one closed capsule to swallow and one open capsule mixed with maple syrup) for 10 days and one closed capsule (probiotics or placebo) per day to swallow for the following 15 days.

Data collection:

A follow-up will be done twice during the acute phase, 14 days and 28 days after starting to take the investigational product to evaluate compliance to treatment, medication intake, side effects, etc. At inclusion and at Day14, Day30 and Day90 after the COVID-19 diagnosis, the participant will complete a questionnaire that will focus on COVID-19 symptoms, food intake, anxiety, functioning difficulties, quality of life, etc. For those who will be admitted to hospital, data on their admission, complications and treatments will be collected.

Samples:

At inclusion and at Day14, Day30 and Day90 after the COVID-19 diagnosis, 2 saliva and 2 stool (viral and microbiota analyzes) self-samples will be performed.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

618 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Evaluation of the Efficacy of Probiotics Taken During the Acute Phase of COVID-19 to Reduce the Occurrence of Long COVID

Actual Study Start Date :

Oct 28, 2021

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Aug 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Probiotics Two probiotic strains will constitute the experimental arm (Probiotics). Participants will take two capsules per day (one closed capsule to swallow and one open capsule mixed with maple syrup) for 10 days and one closed capsule per day to swallow for the following 15 days. They will stop the treatment if they are admitted to the hospital. The treatment will last a maximum of 25 days.	Dietary Supplement: Probiotics 2 strains 10x10^9 UFC/capsule
Placebo Comparator: Placebo Potato starch and magnesium stearate will constitute the comparator arm (Placebo). Participants will take two capsules per day (one closed capsule to swallow and one open capsule mixed with maple syrup) for 10 days and one closed capsule per day to swallow for the following 15 days. They will stop the treatment if they are admitted to the hospital. The treatment will last a maximum of 25 days.	Dietary Supplement: Placebo Potato starch and magnesium stearate

Arm

Intervention/Treatment

Experimental: Probiotics

Two probiotic strains will constitute the experimental arm (Probiotics). Participants will take two capsules per day (one closed capsule to swallow and one open capsule mixed with maple syrup) for 10 days and one closed capsule per day to swallow for the following 15 days. They will stop the treatment if they are admitted to the hospital. The treatment will last a maximum of 25 days.

Dietary Supplement: Probiotics

2 strains 10x10^9 UFC/capsule

Placebo Comparator: Placebo

Potato starch and magnesium stearate will constitute the comparator arm (Placebo). Participants will take two capsules per day (one closed capsule to swallow and one open capsule mixed with maple syrup) for 10 days and one closed capsule per day to swallow for the following 15 days. They will stop the treatment if they are admitted to the hospital. The treatment will last a maximum of 25 days.

Dietary Supplement: Placebo

Potato starch and magnesium stearate

Outcome Measures

Primary Outcome Measures

Number of patients with long COVID 90 days after the COVID-19 diagnosis [90 days after the COVID-19 diagnosis.]
COVID-19 symptoms (FLU-PRO), anxiety (GAD-7) and functioning difficulties (WG-SS)

Secondary Outcome Measures

Number of patients with long COVID 30 days after the COVID-19 diagnosis [30 days after the COVID-19 diagnosis.]
COVID-19 symptoms (FLU-PRO), anxiety (GAD-7) and functioning difficulties (WG-SS)
Describe and compare the salivary and fecal microbiota of patients on probiotics or placebo according to the progression of long COVID. [Inclusion, Day14, Day30 and Day90 after the COVID-19 diagnosis]
Microbiota analyzes (Metagenomic sequencing).
Compare the salivary and fecal viral load of patients on probiotics or placebo according to the progression of long COVID. [Inclusion, Day14, Day30 and Day90 after the COVID-19 diagnosis]
Viral load analyzes (qPCR).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

18 years and over
≤ 10 days between the COVID-19 diagnosis and the inclusion
Having symptoms of the COVID-19 at inclusion
Living in Quebec for the next 90 days
Self-caring at home
Able to take medication alone
With access to a phone or to the Internet
Able to give informed consent

Exclusion Criteria:

Taking probiotic supplements at inclusion
Taking antibiotics for a reason other than COVID-19 at inclusion
Allergies to soy, lactose, yeast, maltodextrin, vitamin C, potato starch, magnesium stearate, hypromellose or titanium dioxide
Has a chronically weakened immune system (AIDS, lymphoma, chemo-radio-corticosteroid therapy, immunosuppressive pathology)
Was treated with chemo-radio-corticosteroid therapy in the last 6 months
Has active cancer
Taking immunosuppressive drugs (e.g. anti-rejection treatment after organ transplant)
Already participating in another randomized clinical trial
Is pregnant, expects to become pregnant in the next few months or is breastfeeding
Has any other condition that would prevent safe participation in the study