Back to resultsVSL#3® vs Placebo in the Treatment of Fatigue and Other Symptoms in Long Covid (DELong#3) (DELong#3)
Primary Purpose
Long COVID
Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
VSL#3®
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Long COVID focused on measuring Long Covid, Fatigue, Gut Microbioma, Dysbiosis, COVID-19, Coronavirus Infections
Eligibility Criteria
Inclusion Criteria: Age >18; <65 yo Previous diagnosis of SARS-CoV-2 infection, documented by nasopharyngeal or antigenic molecular swab; Not currently be in quarantine or isolation; No antibiotics treatment in the 30 days prior to the trial; Chalder Fatigue Scale (in dichotomous form)>=4 possibly associated with signs and symptoms of Long COVID-19 syndrome: signs and symptoms that develop during or after SARS-CoV-2 infection, which persist for more than 4 weeks and are not reasonably explained otherwise; signs and symptoms include: fatigue, sleep disturbances, cognitive deficits (i.e. brain fogging, loss of concentration and memory, anxiety, depression), strength deficits, arthralgias and myalgias, gastroenterological alterations (reduced appetite, nausea, changes in bowel habits, abdominal pain Exclusion Criteria: Cardiovascular and pulmonary disease with moderately severe organ dysfunction (NYHA>2, Borg scale>=2); Decompensated endocrine and metabolic diseases (child cirrhosis >= B, decompensated hypo/hyperthyroidism, decompensated hypoadrenalism) Diagnosis of FM, CFS/ME, and/or IBS prior to SARS-CoV-2 infection; Confirmed diagnoses of neurological pathologies, psychiatric diseases and cognitive disorders prior to SARS-CoV-2 infection; Previous confirmed diagnosis of chronic musculoskeletal pathologies prior to prior to SARS-CoV-2 infection; Refusal to participate in the study / refusal to process personal data; Pregnancy or breastfeeding; Addiction to alcohol or drugs in previous years; Use of other probiotics during the trial; Use of antibiotics during the trial and in the previous 30 days; Substantial change of diet during the trial; Participation in another clinical study in the previous 30 days or previous participation in this same trial; Known intolerance/hypersensitivity to the investigational drug or to the excipients of the placebo formulation
Sites / Locations
- Fondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
VSL#3®
Placebo
Arm Description
VSL#3® 450 billion sachets, two sachets per day (900 billion of bacteria per day) for 28 days
Placebo sachets, two sachets per day for 28 days
Outcomes
Primary Outcome Measures
Assessment of Fatigue variation after 4 weeks of treatment (t4)
To determine if there is a statistically significant variation in the scores on the Chalder Fatigue Scale between the treated group and the placebo group after 4 weeks of treatment (t4)
Secondary Outcome Measures
Assessment of Fatigue variation after 4 weeks of follow-up (t8)
To determine if there is a statistically significant difference in the scores on the Chalder Fatigue Scale between the treated group and the placebo group after 4 weeks of follow-up
Evaluation of Anxiety and Depression variation after 4 weeks of treatment (t4)
To determine if there is a statistically significant difference in the scores on the Hospital Anxiety and Depression Scale (HAD) between the treated group and to the placebo group after 4 weeks of treatment
Evaluation of Anxiety and Depression variation after 4 weeks of follow-up (t8)
To determine if there is a statistically significant difference in the scores on the Hospital Anxiety and Depression Scale (HAD) between the treated group and to the placebo group after 4 weeks of follow-up
Measurement of Quality of Life variation after 4 weeks of treatment (t4)
To determine if there is a statistically significant difference in the scores on the Short Form Health Survey (SF)-36 between the treated group and placebo group after 4 weeks of treatment
Measurement of Quality of Life variation after 4 weeks of follow-up (t8)
To determine if there is a statistically significant difference in the scores on the Short Form Health Survey (SF)-36 between the treated group and the placebo group after 4 weeks of follow-up
Assessment of Gastrointestinal Symptoms variation after 4 weeks of treatment (t4)
To determine if there is a statistically significant difference in the scores on the Structured Assessment of Gastrointestinal Symptoms Scale (SAGIS) between the placebo group and the treated group after 4 weeks of treatment
Assessment of Gastrointestinal Symptoms variation after4 weeks of follow-up (t8)
To determine if there is a statistically significant difference in the scores on the Structured Assessment of Gastrointestinal Symptoms Scale (SAGIS) between the placebo group and the treated group after 4 weeks of follow-up
Analysis of Somatization variation after 4 weeks of treatment (t4)
To identify the level of somatization of symptoms by comparing the scores on the SCL-12 for the somatization of Symptom Checklist-90 (SCL-90) between the treated group and the placebo group after 4 weeks of treatment
Analysis of Somatization variation after 4 weeks of treatment (t4)
To identify the level of somatization of symptoms by comparing the scores on the SCL-12 for the somatization of Symptom Checklist-90 (SCL-90) between the treated groups and the placebo group after 4 weeks of follow-up
Evaluation of Functional Status variation after 4 weeks of treatment (t4)
To assess the general functional status of the patients by comparing the scores on the Karnofsky Performance Status (KPS) Scale between the treated group and the placebo group after 4 weeks of treatment
Evaluation of Functional Status variation after 4 weeks of follow-up (t8)
To assess the general functional status of the patients by comparing the scores on the Karnofsky Performance Status (KPS) Scale between the treated group and the placebo group after 4 weeks of follow-up
Physician's Assessment of General Health variation after 4 weeks of treatment (t4)
To determine the physician's evaluation of the patient's general state of health using a visual-analogue scale (VAS) and comparing it between the treated group and the placebo group after 4 weeks of treatment
Physician's Assessment of General Health variation after 4 weeks of follow-up (t8)
To determine the physician's evaluation of the patient's general state of health using a visual-analogue scale (VAS) and comparing it between the treated group and the placebo group after 4 weeks of follow-up
Analysis of PBMC and Serum Expression of inflammatory mediators at baseline (t0) and after 4 weeks of treatment (t4)
Evaluation of multiple cytokines and chemokines in plasma samples and of immune cell phenotypes in peripheral blood mononuclear cells (PBMCs)
Investigation of Faecal Microbiota Variation after 4 weeks of treatment (t4)
To analyze the variation of the bacterial component of the faecal microbiota in terms of alpha and beta diversity and explore its correlation with clinical response on fatigue in both the placebo group and the treated group by using. Shotgun metagenomics and 16S sequencing of faecal samples at baseline and after 4 weeks of treatment (t4) generate serial gut microbial taxonomic and bacterial functional profiles.
Full Information
NCT ID
NCT05874089
First Posted
May 21, 2023
Last Updated
May 22, 2023
Sponsor
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
1. Study Identification
Unique Protocol Identification Number
NCT05874089
Brief Title
VSL#3® vs Placebo in the Treatment of Fatigue and Other Symptoms in Long Covid (DELong#3)
Acronym
DELong#3
Official Title
The Role of VSL#3® in the Treatment of Fatigue and Other Symptoms in Long Covid-19 Syndrome: a Randomized, Double-blind, Placebo-controlled Study (DELong#3)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 3, 2022 (Actual)
Primary Completion Date
September 3, 2023 (Anticipated)
Study Completion Date
November 3, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This study aims to evaluate the effectiveness of VSL#3® in reducing Fatigue and other symptoms in Long Covid Syndrome compared to placebo.
Detailed Description
Long Covid syndrome is a chronic condition characterized by persistent symptoms experienced by individuals who have recovered from acute coronavirus disease (COVID-19). Among the various symptoms reported, fatigue stands out as a particularly burdensome and pervasive issue, significantly impacting the quality of life and daily functioning of Long Covid patients. Recent studies report that gut microbiota is altered during acute illness and not restored even after several months from recovery. Based on this evidence, modulation of intestinal microbiota can be considered as a possible therapeutic approach for Long Covid Syndrome. On this basis, the aim of this study is to evaluate efficacy of VSL#3® compared to placebo in reducing Fatigue in Long Covid Symptoms.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Long COVID
Keywords
Long Covid, Fatigue, Gut Microbioma, Dysbiosis, COVID-19, Coronavirus Infections
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
This is a single-center randomized, double-blind, placebo-controlled trial. Patients will be recruited from Long Covid out-patient Clinics at Policlinico di Milano Hospital (Milan, Italy) and randomly assigned (1:1) to receive VSL#3® or placebo at the dosage of 2 sachets/die for 28 days. Fasting blood samples and feces will be collected before (t0) and after treatment (t4). Primary and secondary outcome will be assessed at baseline (t0), end of treatment (t4) and end of follow-up (t8) using validated questionnaires (i.e. CFS- Chalder Fatigue Scale; HAD- Hospital Anxiety and Depression Scale, SF36 - Short Form Health Survey, Structured Assessment of Gastrointestinal Symptoms Scale - SAGIS; Symptoms Check List 12 - SCL-12; Karnofsky Performance Status - KPS; Visual Analogue Scale- VAS). Subject participation in this study will be approximately 10 weeks, which include 2-weeks screening/run in period, 4-weeks treatment period and 4-weeks follow-up period.
Masking
ParticipantInvestigator
Masking Description
Double blinding is achieved by packaging probiotics and placebo in the same sealed and consecutively numbered containers with sachets similar in packaging, smell, and taste. All study participants and on-site study personnel will remain masked for the treatment allocation (randomized controlled trial phase) until database lock and signature of the statistical analysis plan.
Allocation
Randomized
Enrollment
96 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
VSL#3®
Arm Type
Active Comparator
Arm Description
VSL#3® 450 billion sachets, two sachets per day (900 billion of bacteria per day) for 28 days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo sachets, two sachets per day for 28 days
Intervention Type
Dietary Supplement
Intervention Name(s)
VSL#3®
Intervention Description
VSL#3® 450 billions/sachets
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo (for VSL#3®)
Intervention Description
Placebo sachets with maltose, cornstarch and dioxide
Primary Outcome Measure Information:
Title
Assessment of Fatigue variation after 4 weeks of treatment (t4)
Description
To determine if there is a statistically significant variation in the scores on the Chalder Fatigue Scale between the treated group and the placebo group after 4 weeks of treatment (t4)
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Assessment of Fatigue variation after 4 weeks of follow-up (t8)
Description
To determine if there is a statistically significant difference in the scores on the Chalder Fatigue Scale between the treated group and the placebo group after 4 weeks of follow-up
Time Frame
8 weeks
Title
Evaluation of Anxiety and Depression variation after 4 weeks of treatment (t4)
Description
To determine if there is a statistically significant difference in the scores on the Hospital Anxiety and Depression Scale (HAD) between the treated group and to the placebo group after 4 weeks of treatment
Time Frame
4 weeks
Title
Evaluation of Anxiety and Depression variation after 4 weeks of follow-up (t8)
Description
To determine if there is a statistically significant difference in the scores on the Hospital Anxiety and Depression Scale (HAD) between the treated group and to the placebo group after 4 weeks of follow-up
Time Frame
8 weeks
Title
Measurement of Quality of Life variation after 4 weeks of treatment (t4)
Description
To determine if there is a statistically significant difference in the scores on the Short Form Health Survey (SF)-36 between the treated group and placebo group after 4 weeks of treatment
Time Frame
4 weeks
Title
Measurement of Quality of Life variation after 4 weeks of follow-up (t8)
Description
To determine if there is a statistically significant difference in the scores on the Short Form Health Survey (SF)-36 between the treated group and the placebo group after 4 weeks of follow-up
Time Frame
8 weeks
Title
Assessment of Gastrointestinal Symptoms variation after 4 weeks of treatment (t4)
Description
To determine if there is a statistically significant difference in the scores on the Structured Assessment of Gastrointestinal Symptoms Scale (SAGIS) between the placebo group and the treated group after 4 weeks of treatment
Time Frame
4 weeks
Title
Assessment of Gastrointestinal Symptoms variation after4 weeks of follow-up (t8)
Description
To determine if there is a statistically significant difference in the scores on the Structured Assessment of Gastrointestinal Symptoms Scale (SAGIS) between the placebo group and the treated group after 4 weeks of follow-up
Time Frame
8 weeks
Title
Analysis of Somatization variation after 4 weeks of treatment (t4)
Description
To identify the level of somatization of symptoms by comparing the scores on the SCL-12 for the somatization of Symptom Checklist-90 (SCL-90) between the treated group and the placebo group after 4 weeks of treatment
Time Frame
4 weeks
Title
Analysis of Somatization variation after 4 weeks of treatment (t4)
Description
To identify the level of somatization of symptoms by comparing the scores on the SCL-12 for the somatization of Symptom Checklist-90 (SCL-90) between the treated groups and the placebo group after 4 weeks of follow-up
Time Frame
8 weeks
Title
Evaluation of Functional Status variation after 4 weeks of treatment (t4)
Description
To assess the general functional status of the patients by comparing the scores on the Karnofsky Performance Status (KPS) Scale between the treated group and the placebo group after 4 weeks of treatment
Time Frame
4 weeks
Title
Evaluation of Functional Status variation after 4 weeks of follow-up (t8)
Description
To assess the general functional status of the patients by comparing the scores on the Karnofsky Performance Status (KPS) Scale between the treated group and the placebo group after 4 weeks of follow-up
Time Frame
8 weeks
Title
Physician's Assessment of General Health variation after 4 weeks of treatment (t4)
Description
To determine the physician's evaluation of the patient's general state of health using a visual-analogue scale (VAS) and comparing it between the treated group and the placebo group after 4 weeks of treatment
Time Frame
4 weeks
Title
Physician's Assessment of General Health variation after 4 weeks of follow-up (t8)
Description
To determine the physician's evaluation of the patient's general state of health using a visual-analogue scale (VAS) and comparing it between the treated group and the placebo group after 4 weeks of follow-up
Time Frame
8 weeks
Title
Analysis of PBMC and Serum Expression of inflammatory mediators at baseline (t0) and after 4 weeks of treatment (t4)
Description
Evaluation of multiple cytokines and chemokines in plasma samples and of immune cell phenotypes in peripheral blood mononuclear cells (PBMCs)
Time Frame
4 weeks
Title
Investigation of Faecal Microbiota Variation after 4 weeks of treatment (t4)
Description
To analyze the variation of the bacterial component of the faecal microbiota in terms of alpha and beta diversity and explore its correlation with clinical response on fatigue in both the placebo group and the treated group by using. Shotgun metagenomics and 16S sequencing of faecal samples at baseline and after 4 weeks of treatment (t4) generate serial gut microbial taxonomic and bacterial functional profiles.
Time Frame
4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age >18; <65 yo
Previous diagnosis of SARS-CoV-2 infection, documented by nasopharyngeal or antigenic molecular swab;
Not currently be in quarantine or isolation;
No antibiotics treatment in the 30 days prior to the trial;
Chalder Fatigue Scale (in dichotomous form)>=4 possibly associated with signs and symptoms of Long COVID-19 syndrome: signs and symptoms that develop during or after SARS-CoV-2 infection, which persist for more than 4 weeks and are not reasonably explained otherwise; signs and symptoms include: fatigue, sleep disturbances, cognitive deficits (i.e. brain fogging, loss of concentration and memory, anxiety, depression), strength deficits, arthralgias and myalgias, gastroenterological alterations (reduced appetite, nausea, changes in bowel habits, abdominal pain
Exclusion Criteria:
Cardiovascular and pulmonary disease with moderately severe organ dysfunction (NYHA>2, Borg scale>=2);
Decompensated endocrine and metabolic diseases (child cirrhosis >= B, decompensated hypo/hyperthyroidism, decompensated hypoadrenalism)
Diagnosis of FM, CFS/ME, and/or IBS prior to SARS-CoV-2 infection;
Confirmed diagnoses of neurological pathologies, psychiatric diseases and cognitive disorders prior to SARS-CoV-2 infection;
Previous confirmed diagnosis of chronic musculoskeletal pathologies prior to prior to SARS-CoV-2 infection;
Refusal to participate in the study / refusal to process personal data;
Pregnancy or breastfeeding;
Addiction to alcohol or drugs in previous years;
Use of other probiotics during the trial;
Use of antibiotics during the trial and in the previous 30 days;
Substantial change of diet during the trial;
Participation in another clinical study in the previous 30 days or previous participation in this same trial;
Known intolerance/hypersensitivity to the investigational drug or to the excipients of the placebo formulation
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Flavio Caprioli, MD, PhD
Phone
+39 02 5503 2141
Email
flavio.caprioli@policlinico.mi.it
First Name & Middle Initial & Last Name or Official Title & Degree
Beatrice Marinoni, MD
Phone
+39 02 5503 2141
Email
beatrice.marinoni@unimi.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Flavio Caprioli, MD, PhD
Organizational Affiliation
Fondazione IRCCS Cà Granda, Ospedale Policlinico di Milano
Official's Role
Study Director
Facility Information:
Facility Name
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
City
Milan
State/Province
MI
ZIP/Postal Code
20122
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Beatrice Marinoni, MD
Phone
+39 02 5503 2141
Email
beatrice.marinoni@unimi.it
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Citation
Zuo T, Zhang F, Lui GCY, Yeoh YK, Li AYL, Zhan H, Wan Y, Chung ACK, Cheung CP, Chen N, Lai CKC, Chen Z, Tso EYK, Fung KSC, Chan V, Ling L, Joynt G, Hui DSC, Chan FKL, Chan PKS, Ng SC. Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization. Gastroenterology. 2020 Sep;159(3):944-955.e8. doi: 10.1053/j.gastro.2020.05.048. Epub 2020 May 20.
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VSL#3® vs Placebo in the Treatment of Fatigue and Other Symptoms in Long Covid (DELong#3)
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