Clinical trial NCT05556733: FMT for Post-acute COVID-19 Syndrome
Official title: Faecal Microbiota Transplantation for Post-acute COVID-19 Syndrome: a Pilot Open-label Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Post-Acute COVID19 Syndrome
COVID-19
Keywords: Faecal Microbiota Transplantation
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2022-09-27
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The intervention group will receive FMT while the control group will not receive FMT.
Primary purpose: TREATMENT

Brief summary: In recovered COVID-19 patients, emerging global data have reported the presence of long COVID, that is, at least one symptom that an alternative diagnosis cannot explain has been persistent for four or more weeks after the initial infection. We demonstrated previously that almost 80% of recovered COVID-19 patients in Hong Kong suffer from Long COVID for more than 6 months, affecting multiple body systems.

In a recent study, the five most common Long COVID symptoms were fatigue, memory problem, difficulty sleeping, anxiety and hair loss. One promising hypothesis is the involvement of the gut microbiota, a collection of the trillions of gut microorganisms that play important immunomodulatory roles against infections.

Faecal microbiota transplantation (FMT), which is the infusion of processed faeces from healthy donors to the gut of affected subjects, has shown impressive therapeutic effects for recurrent Clostridioides difficile infection and other emerging indications. Gut microorganisms together with the metabolites in the donated faeces could potentially modulate the gut microbiota of the recipient and treat the dysbiosis associated with pathological health conditions. To date, no study has yet to assess the therapeutic effects of FMT in post-COVID-19 neuropsychiatric conditions.

Detailed description: Coronavirus Disease 2019 (COVID-19) is the disease caused by a novel coronavirus SARS- CoV-2. In recovered COVID-19 patients, emerging global data have reported the presence of Long COVID, a condition where at least one symptom that cannot be explained by alternative diagnosis has been persistent for four or more weeks after the initial infection. We demonstrated previously that almost 80% of recovered COVID-19 patients in Hong Kong suffer from Long COVID for more than 6 months, affecting multiple body systems.

In a recent study, the five most common Long COVID symptoms were fatigue, memory problem, difficulty sleeping, anxiety and hair loss. Current treatment for Long COVID only involves symptomatic care, as the exact mechanisms underlying the pathogenesis are still largely unknown. One promising hypothesis is the involvement of the gut microbiota, a collection of the trillions of gut microorganisms that play important immunomodulatory roles against infections. Our recently published findings have shown that patients with Long COVID had a less diverse gut microbiota with significantly fewer health-associated commensal bacteria than those without Long COVID. Previous studies have also proved the association between the gut microbiota and insomnia, circadian disturbance and affective disorders. Thus, gut microbiota modulation could be a novel therapeutic strategy for these neuropsychiatric conditions.

Faecal microbiota transplantation (FMT), which is the infusion of faeces from healthy donors to the gut of affected subjects, has shown impressive therapeutic effects for various diseases. To date, no study has yet to assess the therapeutic effects of FMT in post-COVID-19 neuropsychiatric conditions. In this pilot open-label study, we aim to explore the efficacy of FMT in improving neuropsychiatric symptoms including but not limited to insomnia severity, sleep quality, anxiety and fatigue in recovered COVID-19 patients. FMT will be administrated via Oesophago-gastro-duodenoscopy (OGD) and Flexible Sigmoidoscopy (FS). Two arms will be recruited in a 1:1 ratio. The intervention group will receive FMT while the control group will not receive FMT. Both groups will have the same assessments. Subjects will receive FMT via OGD at week 0, week 2, week 4 and week 8, and via FS at week 0. Final follow-up will be scheduled at weeks 8 and 12 for clinical assessment. To assess the efficacy of FMT in improving neuropsychiatric symptoms, subjects will have to fill in study questionnaires at baseline, week 8 and week 12. Subjects will also be asked to fill in a sleep diary daily until week 12.

Eligibility criteria: Both the interventional group and control group will meet the criteria below and the control group will be age- and sex-matched subjects with the interventional group.

Inclusion Criteria:

* Individuals aged 18 and above
* Subjects who were recovered cases of COVID-19 confirmed by RT-PCR or rapid antigen test (RAT)
* Subjects who had insomnia symptoms of post-acute COVID-19 syndrome at screening visit

Exclusion Criteria:

* Confirmed current active malignancy
* Had abdominal surgery
* Known history of severe organ failure (including decompensated cirrhosis), renal failure on dialysis, suffering from human immunodeficiency virus infection;
* Known pregnancy
* Mental retardation or inability to provide informed consent
* Contraindications to upper GI endoscopy

Primary outcomes:
measure: Change in insomnia severity
timeFrame: 12 weeks
Secondary outcomes:
measure: Change in sleep quality
timeFrame: 12 weeks
measure: Change in anxiety symptoms
timeFrame: 12 weeks
measure: Change in daytime sleepiness
timeFrame: 12 weeks
measure: Change in fatigue symptoms
timeFrame: 12 weeks
measure: Change in sleep diary parameters
timeFrame: 12 weeks
measure: Change in gut microbiota composition
timeFrame: 12 weeks
measure: Change in gut microbiota diversity and richness
timeFrame: 12 weeks
measure: Similarity of gut microbiota composition to donor
timeFrame: 12 weeks
measure: Change in blood cytokine profile
timeFrame: 12 weeks
measure: Change in blood cortisol
timeFrame: 12 weeks
measure: Change in Melatonin level
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
Study officials:
affiliation: Chinese University of Hong Kong
name: Siew Chien Ng, PhD, FRCP
role: PRINCIPAL_INVESTIGATOR
References:
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