FMT-PACS: FMT for Post-acute COVID-19 Syndrome

Sponsor
Chinese University of Hong Kong (Other)
Overall Status
Recruiting
CT.gov ID
NCT05556733
Collaborator
(none)
60
1
2
21.1
2.8

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Procedure: Faecal Microbiota Transplantation
N/A

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
The intervention group will receive FMT while the control group will not receive FMT.The intervention group will receive FMT while the control group will not receive FMT.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Faecal Microbiota Transplantation for Post-acute COVID-19 Syndrome: a Pilot Open-label Study
Actual Study Start Date :
Sep 28, 2022
Anticipated Primary Completion Date :
Aug 31, 2023
Anticipated Study Completion Date :
Jun 30, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Faecal Microbiota Transplantation

Subjects will receive Faecal Microbiota Transplantation

Procedure: Faecal Microbiota Transplantation
FMT at baseline, week 2, week 4, week 8

No Intervention: Control

The control subjects will not receive FMT

Outcome Measures

Primary Outcome Measures

  1. Change in long COVID symptoms [12 weeks]

    A 13-item self-report questionnaire will be used to evaluate whether 13 common long COVID symptoms are improved, unchanged or worsened after intervention. Symptoms include fatigue, memory problem, difficulty concentrating, difficulty sleeping, anxiety or sadness, hair loss, shortness of breath, coughing, inability to exercise, chest pain, muscle pain, joint pain and digestive problems.

Secondary Outcome Measures

  1. Change in insomnia severity [12 weeks]

    Severity of insomnia will be measured by a 7-item Insomnia Severity Index (ISI). ISI is a self-report questionnaire used to evaluate the nature, severity and impact of insomnia. Total score ranges from 0 to 28. Higher score indicates more severe insomnia.

  2. Change in sleep quality [12 weeks]

    Quality of sleep will be measured by a 19-item Pittsburgh Sleep Quality Index (PSQI). PSQI is a self-report questionnaire used to evaluate sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. Total score ranges from 0 to 21. Lower score indicates healthier sleep quality.

  3. Change in anxiety symptoms [12 weeks]

    Anxiety symptoms will be assessed by a 7-item Generalised Anxiety Disorder-7 scale (GAD-7). GAD-7 is a widely used diagnostic self-report scale for the screening, diagnosis and severity assessment of anxiety disorder. Total score ranges from 0 to 21. Higher score indicates more severe anxiety.

  4. Change in daytime sleepiness [12 weeks]

    Daytime sleepiness will be measured by a 8-item Epworth Sleepiness Scale (ESS). ESS is a widely used self-report questionnaire used to evaluate daytime sleepiness in the field of sleep medicine. Total score ranges from 0 to 24. Higher score indicates more daytime sleepiness.

  5. Change in fatigue symptoms [12 weeks]

    Fatigue symptoms will be assessed by a 20-item Multidimensional Fatigue Inventory (MFI). MFI is a self-report questionnaire used to evaluate five dimensions of fatigue, including general fatigue, physical fatigue, mental fatigue, reduced motivation and reduced activity. Each dimension has four items. Total score of each dimension ranges from 4 to 20. Higher score indicates more severe fatigue for that dimension.

  6. Change in sleep diary parameters [12 weeks]

    Consensus Sleep Diary (CSD) will be used to record sleep time, wake time and subjective sleeping quality daily. Parameters including sleep onset latency, time awake after sleep onset, total wake time, total sleep time and sleep efficiency will be calculated.

  7. Change in gut microbiota composition [12 weeks]

    Relative abundance of gut bacteria at species level will be assessed by metagenomic analysis.

  8. Change in gut microbiota diversity and richness [12 weeks]

    Species diversity (Shannon index) and richness (number of observed species) will be calculated based on the relative abundance of gut bacteria.

  9. Similarity of gut microbiota composition to donor [12 weeks]

    Engraftment of donor species after intervention will be assessed by the similarity of gut microbiota composition to the donor.

  10. Change in blood cytokine profile [12 weeks]

    Change in blood cytokine profile will be assessed, including levels of interferon gamma, interleukins, leptin, vascular endothelial growth factor, membrane-bound immunoglobulin, and tumour necrosis factor-α etc.

  11. Change in blood cortisol [12 weeks]

    Change in blood cortisol will be assessed

  12. Change in Melatonin level [12 weeks]

    Change in blood melatonin will be assessed

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No

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 neurocognitive symptoms of post-acute COVID-19 syndrome consisting of insomnia, poor sleep, anxiety or fatigue 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Prince of Wales Hospital Hong Kong Hong Kong

Sponsors and Collaborators

  • Chinese University of Hong Kong

Investigators

  • Principal Investigator: Siew Chien Ng, PhD, FRCP, Chinese University of Hong Kong

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Siew Chien NG, Professor Siew Chien NG, Chinese University of Hong Kong
ClinicalTrials.gov Identifier:
NCT05556733
Other Study ID Numbers:
  • FMT-PACS
First Posted:
Sep 27, 2022
Last Update Posted:
Jan 5, 2023
Last Verified:
Jan 1, 2023
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Siew Chien NG, Professor Siew Chien NG, Chinese University of Hong Kong
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jan 5, 2023