Clinical trial NCT05874089: VSL#3® vs Placebo in the Treatment of Fatigue and Other Symptoms in Long Covid (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
Overall status: UNKNOWN
Phase: NA
Conditions: Long COVID
Keywords: Long Covid
Fatigue
Gut Microbioma
Dysbiosis
COVID-19
Coronavirus Infections
Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Sponsor class: OTHER
First posted: 2023-05-24
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Assessment of Fatigue variation after 4 weeks of treatment (t4)
timeFrame: 4 weeks
Secondary outcomes:
measure: Assessment of Fatigue variation after 4 weeks of follow-up (t8)
timeFrame: 8 weeks
measure: Evaluation of Anxiety and Depression variation after 4 weeks of treatment (t4)
timeFrame: 4 weeks
measure: Evaluation of Anxiety and Depression variation after 4 weeks of follow-up (t8)
timeFrame: 8 weeks
measure: Measurement of Quality of Life variation after 4 weeks of treatment (t4)
timeFrame: 4 weeks
measure: Measurement of Quality of Life variation after 4 weeks of follow-up (t8)
timeFrame: 8 weeks
measure: Assessment of Gastrointestinal Symptoms variation after 4 weeks of treatment (t4)
timeFrame: 4 weeks
measure: Assessment of Gastrointestinal Symptoms variation after4 weeks of follow-up (t8)
timeFrame: 8 weeks
measure: Analysis of Somatization variation after 4 weeks of treatment (t4)
timeFrame: 4 weeks
measure: Analysis of Somatization variation after 4 weeks of treatment (t4)
timeFrame: 8 weeks
measure: Evaluation of Functional Status variation after 4 weeks of treatment (t4)
timeFrame: 4 weeks
measure: Evaluation of Functional Status variation after 4 weeks of follow-up (t8)
timeFrame: 8 weeks
measure: Physician's Assessment of General Health variation after 4 weeks of treatment (t4)
timeFrame: 4 weeks
measure: Physician's Assessment of General Health variation after 4 weeks of follow-up (t8)
timeFrame: 8 weeks
measure: Analysis of PBMC and Serum Expression of inflammatory mediators at baseline (t0) and after 4 weeks of treatment (t4)
timeFrame: 4 weeks
measure: Investigation of Faecal Microbiota Variation after 4 weeks of treatment (t4)
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
state: MI
Study officials:
affiliation: Fondazione IRCCS Cà Granda, Ospedale Policlinico di Milano
name: Flavio Caprioli, MD, PhD
role: STUDY_DIRECTOR
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