Efficacy of Lactobacillus Paracasei PS23 for Patients With Post-COVID-19 Syndrome

Study Overview
=================
Brief Summary
-----------------
To evaluate whether probiotics PS23 can improve the symptoms of patients with long COVID-19 ; also to evaluate the effects on blood cortisol and inflammation-related indicators in patients.

Detailed Description
-----------------
It is expected that a total of 120 subjects will be recruited within 3 years after IRB approval, divided into two groups of 60 subjects, respectively consuming PS23 heat-treated bacteria or placebo, and completing the 6-week period.

Official Title
-----------------
Efficacy of Lactobacillus Paracasei PS23 for Patients With Post-COVID-19 Syndrome

Conditions
-----------------
Post-COVID-19 Syndrome

Intervention / Treatment
-----------------
* Dietary Supplement: PS23 heat-treated


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged above 20 years old and below 65 years old. Those who consciously have long COVID-19 symptoms or actively respond to website advertisements to express interest in participating in this clinical researcher. Those who received the confirmation SMS or the COVID-19 rapid test positive 4 weeks ago. Exclusion Criteria: Have taken antibiotics within one month or are receiving antibiotic treatment. Have taken probiotic products have been used within two weeks (excluding yogurt, yogurt, Yakult and other related foods). Cancer or immunocompromised patients undergoing treatment. Those who are allergic to lactic acid bacteria products. Diagnosed with dementia before being diagnosed with COVID-19. Prior to or currently taking medication for acute or psychiatric illness prior to the diagnosis of COVID-19. The investigator judges that it is not suitable to participate in the researcher.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Heat-treated PS23<br>PS23 heat-treated, 2 caps daily use | Dietary Supplement: PS23 heat-treated<br>* PS23 heat-treated, 2 caps daily use<br>|
| Placebo Comparator: Placebo<br>The placebo , 2 caps daily use | Dietary Supplement: PS23 heat-treated<br>* PS23 heat-treated, 2 caps daily use<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression scales of Severity rated by clinician（CGI） | The CGIC is a single-item questionnaire that asks the investigator to assess a patient's TD symptoms at specific visits after initiating therapy. The CGIC uses a 7 point Likert Scale, ranging from very much worse (-3) to very much improved (+3), to assess overall response to therapy. A treatment success was defined as much improved or very much improved at the week 6 visit. | From Baseline to 6 Weeks Assessed | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wechsler Adult Intelligence Scale 4th version | The WAIS-IV is a measure of cognitive function in older adolescents and adults. Participants complete the Digit Span subtest, which measures auditory working memory for numerical information. | From Baseline to 6 Weeks Assessed | 
| Color Trails Test（CTT） | There are two subtests: CTT1 & CTT2. The time spend to complete the two subtest is used representing executive function of the participants. | From Baseline to 6 Weeks Assessed | 
| Insomnia Severity Index（ISI） | The Insomnia Severity Index (ISI) is a brief instrument that was designed to assess the severity of both nighttime and daytime components of insomnia. | From Baseline to 6 Weeks Assessed | 
| The Quality of Life, Enjoyment, and Satisfaction Questionnaire-16, QLESQ-16 | The Quality of Life, Enjoyment, and Satisfaction Questionnaire-16 (QLESQ-16) is a valid, reliable self-report instrument for assessing quality of life. | From Baseline to 6 Weeks Assessed | 
| State and Trait Anxiety Index (STAI) | The State-Trait Anxiety Inventory (STAI) is a commonly used measure of trait and state anxiety. All items are rated on a 4-point scale (e.g., from Almost Never to Almost Always). Higher scores indicate greater anxiety. | From Baseline to 6 Weeks Assessed | 
| Patient Heath Questionnaire-9 (PHQ-9) | The PHQ-9 is a multipurpose instrument for screening, diagnosing, monitoring and measuring the severity of depression: The PHQ-9 incorporates DSM-IV depression diagnostic criteria with other leading major depressive symptoms into a brief self-report tool.Depression Severity: 0- none, 1-4 minimal, 5-9 mild, 10-14 moderate, 15-19 moderately severe, 20-27 severe. Validity has been assessed against an independent structured mental health professional (MHP) interview. PHQ-9 score ≥10 had a sensitivity of 88% and a specificity of 88% for major depression. | From Baseline to 6 Weeks Assessed | 
| Visual Analogue Scale-GI (VAS-GI) | Visual Analogue Scale for GI symptoms, VAS-GI (visual analogue scale, VAS 0-10) was designed to measure the response of symptoms and well-being in patients after taking probiotics or placebo. | From Baseline to 6 Weeks Assessed | 
| Patient Global Impression scales of Improvement rated by patient（PGI-C） | The PGIC consists of one item taken from the clinical global impression and adapted to the patient. The minimum total score possible is 1 and the maximum total score possible is 7. Higher values represent a worse outcome. | From Baseline to 6 Weeks Assessed |