Long COVIDDELong#3NCT05874089
VSL#3® vs Placebo in the Treatment of Fatigue and Other Symptoms in Long Covid (DELong#3)
A study testing VSL#3® in people with Long COVID, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.
Trial summary
This study aims to evaluate the effectiveness of VSL#3® in reducing Fatigue and other symptoms in Long Covid Syndrome compared to placebo. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Long COVID
- What is being tested?
- VSL#3®
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 96 participants
- Where
- 1 siteItaly
- Study dates
- 3 Nov 2022to 3 Nov 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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;
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- 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
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, MI, 20122
Beatrice Marinoni, MD, +39 02 5503 2141, beatrice.marinoni@unimi.it
About this study
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)
This study aims to evaluate the effectiveness of VSL#3® in reducing Fatigue and other symptoms in Long Covid Syndrome compared to placebo.
Read the 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.
- Conditions
- Long COVID
- Being tested
- VSL#3®, Placebo
- Keywords
- Long Covid, Fatigue, Gut Microbioma, Dysbiosis, COVID-19, Coronavirus Infections
- Medical subject headings
- Post-Acute COVID-19 Syndrome, Fatigue, Dysbiosis, COVID-19, Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VSL#3®Dietary supplement
VSL#3® 450 billions/sachets
PlaceboDietary supplement
Also called Placebo (for VSL#3®)
Placebo sachets with maltose, cornstarch and dioxide
| Study group | Role | What they receive |
|---|---|---|
| VSL#3® | Active comparator | VSL#3® 450 billion sachets, two sachets per day (900 billion of bacteria per day) for 28 days Receives: Dietary Supplement: VSL#3® |
| Placebo | Placebo comparator | Placebo sachets, two sachets per day for 28 days Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 4 weeks
Secondary outcomes (15)
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
Measured: 8 weeks
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
Measured: 4 weeks
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
Measured: 8 weeks
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
Measured: 4 weeks
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
Measured: 8 weeks
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
Measured: 4 weeks
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
Measured: 8 weeks
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
Measured: 4 weeks
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
Measured: 8 weeks
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
Measured: 4 weeks
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
Measured: 8 weeks
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
Measured: 4 weeks
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
Measured: 8 weeks
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)
Measured: 4 weeks
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.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2023
- Study start3 Nov 2022
- Primary completion3 Sep 2023 (estimated)
- Study completion3 Nov 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Long COVIDStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Flavio Caprioli, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
- Investigators
- Flavio Caprioli, MD, PhD, Study director, Fondazione IRCCS Cà Granda, Ospedale Policlinico di Milano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05874089
- Sponsor's protocol ID
- DELong#3
- Acronym
- DELong#3
- Status last verified
- May 2023
- First submitted
- 21 May 2023
- Last updated
- 24 May 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Ancona G, Alagna L, Alteri C, Palomba E, Tonizzo A, Pastena A, Muscatello A, Gori A, Bandera A. Gut and airway microbiota dysbiosis and their role in COVID-19 and long-COVID. Front Immunol. 2023 Mar 8;14:1080043. doi: 10.3389/fimmu.2023.1080043. eCollection 2023.
PubMed 36969243Chalder T, Berelowitz G, Pawlikowska T, Watts L, Wessely S, Wright D, Wallace EP. Development of a fatigue scale. J Psychosom Res. 1993;37(2):147-53. doi: 10.1016/0022-3999(93)90081-p.
PubMed 8463991Ceban F, Ling S, Lui LMW, Lee Y, Gill H, Teopiz KM, Rodrigues NB, Subramaniapillai M, Di Vincenzo JD, Cao B, Lin K, Mansur RB, Ho RC, Rosenblat JD, Miskowiak KW, Vinberg M, Maletic V, McIntyre RS. Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis. Brain Behav Immun. 2022 Mar;101:93-135. doi: 10.1016/j.bbi.2021.12.020. Epub 2021 Dec 29.
PubMed 34973396Chen Y, Gu S, Chen Y, Lu H, Shi D, Guo J, Wu WR, Yang Y, Li Y, Xu KJ, Ding C, Luo R, Huang C, Yu L, Xu M, Yi P, Liu J, Tao JJ, Zhang H, Lv L, Wang B, Sheng J, Li L. Six-month follow-up of gut microbiota richness in patients with COVID-19. Gut. 2022 Jan;71(1):222-225. doi: 10.1136/gutjnl-2021-324090. Epub 2021 Apr 8. No abstract available.
PubMed 33833065Choutka J, Jansari V, Hornig M, Iwasaki A. Unexplained post-acute infection syndromes. Nat Med. 2022 May;28(5):911-923. doi: 10.1038/s41591-022-01810-6. Epub 2022 May 18.
PubMed 35585196Davis HE, McCorkell L, Vogel JM, Topol EJ. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. 2023 Mar;21(3):133-146. doi: 10.1038/s41579-022-00846-2. Epub 2023 Jan 13.
PubMed 36639608Farsi Y, Tahvildari A, Arbabi M, Vazife F, Sechi LA, Shahidi Bonjar AH, Jamshidi P, Nasiri MJ, Mirsaeidi M. Diagnostic, Prognostic, and Therapeutic Roles of Gut Microbiota in COVID-19: A Comprehensive Systematic Review. Front Cell Infect Microbiol. 2022 Mar 4;12:804644. doi: 10.3389/fcimb.2022.804644. eCollection 2022.
PubMed 35310853Fernandez-de-Las-Penas C, Rodriguez-Jimenez J, Cancela-Cilleruelo I, Guerrero-Peral A, Martin-Guerrero JD, Garcia-Azorin D, Cornejo-Mazzuchelli A, Hernandez-Barrera V, Pellicer-Valero OJ. Post-COVID-19 Symptoms 2 Years After SARS-CoV-2 Infection Among Hospitalized vs Nonhospitalized Patients. JAMA Netw Open. 2022 Nov 1;5(11):e2242106. doi: 10.1001/jamanetworkopen.2022.42106.
PubMed 36378309Giannos P, Prokopidis K. Gut dysbiosis and long COVID-19: Feeling gutted. J Med Virol. 2022 Jul;94(7):2917-2918. doi: 10.1002/jmv.27684. Epub 2022 Mar 7. No abstract available.
PubMed 35233795Global Burden of Disease Long COVID Collaborators; Wulf Hanson S, Abbafati C, Aerts JG, Al-Aly Z, Ashbaugh C, Ballouz T, Blyuss O, Bobkova P, Bonsel G, Borzakova S, Buonsenso D, Butnaru D, Carter A, Chu H, De Rose C, Diab MM, Ekbom E, El Tantawi M, Fomin V, Frithiof R, Gamirova A, Glybochko PV, Haagsma JA, Haghjooy Javanmard S, Hamilton EB, Harris G, Heijenbrok-Kal MH, Helbok R, Hellemons ME, Hillus D, Huijts SM, Hultstrom M, Jassat W, Kurth F, Larsson IM, Lipcsey M, Liu C, Loflin CD, Malinovschi A, Mao W, Mazankova L, McCulloch D, Menges D, Mohammadifard N, Munblit D, Nekliudov NA, Ogbuoji O, Osmanov IM, Penalvo JL, Petersen MS, Puhan MA, Rahman M, Rass V, Reinig N, Ribbers GM, Ricchiuto A, Rubertsson S, Samitova E, Sarrafzadegan N, Shikhaleva A, Simpson KE, Sinatti D, Soriano JB, Spiridonova E, Steinbeis F, Svistunov AA, Valentini P, van de Water BJ, van den Berg-Emons R, Wallin E, Witzenrath M, Wu Y, Xu H, Zoller T, Adolph C, Albright J, Amlag JO, Aravkin AY, Bang-Jensen BL, Bisignano C, Castellano R, Castro E, Chakrabarti S, Collins JK, Dai X, Daoud F, Dapper C, Deen A, Duncan BB, Erickson M, Ewald SB, Ferrari AJ, Flaxman AD, Fullman N, Gamkrelidze A, Giles JR, Guo G, Hay SI, He J, Helak M, Hulland EN, Kereselidze M, Krohn KJ, Lazzar-Atwood A, Lindstrom A, Lozano R, Malta DC, Mansson J, Mantilla Herrera AM, Mokdad AH, Monasta L, Nomura S, Pasovic M, Pigott DM, Reiner RC Jr, Reinke G, Ribeiro ALP, Santomauro DF, Sholokhov A, Spurlock EE, Walcott R, Walker A, Wiysonge CS, Zheng P, Bettger JP, Murray CJL, Vos T. Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021. JAMA. 2022 Oct 25;328(16):1604-1615. doi: 10.1001/jama.2022.18931.
PubMed 36215063Guo C, Che X, Briese T, Ranjan A, Allicock O, Yates RA, Cheng A, March D, Hornig M, Komaroff AL, Levine S, Bateman L, Vernon SD, Klimas NG, Montoya JG, Peterson DL, Lipkin WI, Williams BL. Deficient butyrate-producing capacity in the gut microbiome is associated with bacterial network disturbances and fatigue symptoms in ME/CFS. Cell Host Microbe. 2023 Feb 8;31(2):288-304.e8. doi: 10.1016/j.chom.2023.01.004.
PubMed 36758522Li N, Ma WT, Pang M, Fan QL, Hua JL. The Commensal Microbiota and Viral Infection: A Comprehensive Review. Front Immunol. 2019 Jul 4;10:1551. doi: 10.3389/fimmu.2019.01551. eCollection 2019.
PubMed 31333675Marasco G, Cremon C, Barbaro MR, Cacciari G, Falangone F, Kagramanova A, Bordin D, Drug V, Miftode E, Fusaroli P, Mohamed SY, Ricci C, Bellini M, Rahman MM, Melcarne L, Santos J, Lobo B, Bor S, Yapali S, Akyol D, Sapmaz FP, Urun YY, Eskazan T, Celebi A, Kacmaz H, Ebik B, Binicier HC, Bugdayci MS, Yagci MB, Pullukcu H, Kaya BY, Tureyen A, Hatemi I, Koc ES, Sirin G, Caliskan AR, Bengi G, Alis EE, Lukic S, Trajkovska M, Hod K, Dumitrascu D, Pietrangelo A, Corradini E, Simren M, Sjolund J, Tornkvist N, Ghoshal UC, Kolokolnikova O, Colecchia A, Serra J, Maconi G, De Giorgio R, Danese S, Portincasa P, Di Sabatino A, Maggio M, Philippou E, Lee YY, Salvi D, Venturi A, Borghi C, Zoli M, Gionchetti P, Viale P, Stanghellini V, Barbara G; GI-COVID19 study group. Post COVID-19 irritable bowel syndrome. Gut. 2022 Dec 9:gutjnl-2022-328483. doi: 10.1136/gutjnl-2022-328483. Online ahead of print.
PubMed 36591612Nagata N, Takeuchi T, Masuoka H, Aoki R, Ishikane M, Iwamoto N, Sugiyama M, Suda W, Nakanishi Y, Terada-Hirashima J, Kimura M, Nishijima T, Inooka H, Miyoshi-Akiyama T, Kojima Y, Shimokawa C, Hisaeda H, Zhang F, Yeoh YK, Ng SC, Uemura N, Itoi T, Mizokami M, Kawai T, Sugiyama H, Ohmagari N, Ohno H. Human Gut Microbiota and Its Metabolites Impact Immune Responses in COVID-19 and Its Complications. Gastroenterology. 2023 Feb;164(2):272-288. doi: 10.1053/j.gastro.2022.09.024. Epub 2022 Sep 23.
PubMed 36155191Sherif ZA, Gomez CR, Connors TJ, Henrich TJ, Reeves WB; RECOVER Mechanistic Pathway Task Force. Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC). Elife. 2023 Mar 22;12:e86002. doi: 10.7554/eLife.86002.
PubMed 36947108
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05874089
- Acronym / sponsor ID
- DELong#3 / DELong#3
- Conditions
- Long COVID
- Keywords
- Long Covid, Fatigue, Gut Microbioma, Dysbiosis, COVID-19, Coronavirus Infections
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoUniversity, hospital or other
- Study start
- 3 Nov 2022 (actual)
- Primary completion
- 3 Sep 2023 (estimated)
- Study completion
- 3 Nov 2023 (estimated)
- First posted
- 24 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| VSL#3® | Active comparator | Dietary Supplement: VSL#3®VSL#3® 450 billion sachets, two sachets per day (900 billion of bacteria per day) for 28 days |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboPlacebo sachets, two sachets per day for 28 days |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (13 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VSL#3®VSL#3® 450 billions/sachets | Dietary supplement | VSL#3® |
| PlaceboAlso: Placebo (for VSL#3®)Placebo sachets with maltose, cornstarch and dioxide | Dietary supplement | Placebo |
Primary outcome
Assessment of Fatigue variation after 4 weeks of treatment (t4)
Time frame: 4 weeks
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)
15 secondary outcomes
Assessment of Fatigue variation after 4 weeks of follow-up (t8)
Time frame: 8 weeks
Evaluation of Anxiety and Depression variation after 4 weeks of treatment (t4)
Time frame: 4 weeks
Evaluation of Anxiety and Depression variation after 4 weeks of follow-up (t8)
Time frame: 8 weeks
Measurement of Quality of Life variation after 4 weeks of treatment (t4)
Time frame: 4 weeks
Measurement of Quality of Life variation after 4 weeks of follow-up (t8)
Time frame: 8 weeks
Assessment of Gastrointestinal Symptoms variation after 4 weeks of treatment (t4)
Time frame: 4 weeks
Assessment of Gastrointestinal Symptoms variation after4 weeks of follow-up (t8)
Time frame: 8 weeks
Analysis of Somatization variation after 4 weeks of treatment (t4)
Time frame: 4 weeks
Analysis of Somatization variation after 4 weeks of treatment (t4)
Time frame: 8 weeks
Evaluation of Functional Status variation after 4 weeks of treatment (t4)
Time frame: 4 weeks
Evaluation of Functional Status variation after 4 weeks of follow-up (t8)
Time frame: 8 weeks
Physician's Assessment of General Health variation after 4 weeks of treatment (t4)
Time frame: 4 weeks
Physician's Assessment of General Health variation after 4 weeks of follow-up (t8)
Time frame: 8 weeks
Analysis of PBMC and Serum Expression of inflammatory mediators at baseline (t0) and after 4 weeks of treatment (t4)
Time frame: 4 weeks
Investigation of Faecal Microbiota Variation after 4 weeks of treatment (t4)
Time frame: 4 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2023.
- Background: PubMed 36969243Ancona G, Alagna L, Alteri C, Palomba E, Tonizzo A, Pastena A, Muscatello A, Gori A, Bandera A. Gut and airway microbiota dysbiosis and their role in COVID-19 and long-COVID. Front Immunol. 2023 Mar 8;14:1080043. doi: 10.3389/fimmu.2023.1080043. eCollection 2023.
- Background: PubMed 8463991Chalder T, Berelowitz G, Pawlikowska T, Watts L, Wessely S, Wright D, Wallace EP. Development of a fatigue scale. J Psychosom Res. 1993;37(2):147-53. doi: 10.1016/0022-3999(93)90081-p.
- Background: PubMed 34973396Ceban F, Ling S, Lui LMW, Lee Y, Gill H, Teopiz KM, Rodrigues NB, Subramaniapillai M, Di Vincenzo JD, Cao B, Lin K, Mansur RB, Ho RC, Rosenblat JD, Miskowiak KW, Vinberg M, Maletic V, McIntyre RS. Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis. Brain Behav Immun. 2022 Mar;101:93-135. doi: 10.1016/j.bbi.2021.12.020. Epub 2021 Dec 29.
- Background: PubMed 33833065Chen Y, Gu S, Chen Y, Lu H, Shi D, Guo J, Wu WR, Yang Y, Li Y, Xu KJ, Ding C, Luo R, Huang C, Yu L, Xu M, Yi P, Liu J, Tao JJ, Zhang H, Lv L, Wang B, Sheng J, Li L. Six-month follow-up of gut microbiota richness in patients with COVID-19. Gut. 2022 Jan;71(1):222-225. doi: 10.1136/gutjnl-2021-324090. Epub 2021 Apr 8. No abstract available.
- Background: PubMed 35585196Choutka J, Jansari V, Hornig M, Iwasaki A. Unexplained post-acute infection syndromes. Nat Med. 2022 May;28(5):911-923. doi: 10.1038/s41591-022-01810-6. Epub 2022 May 18.
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- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Flavio Caprioli, MD, PhD study director
Fondazione IRCCS Cà Granda, Ospedale Policlinico di Milano
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing VSL#3® in people with Long COVID, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Flavio Caprioli, MD, PhD (+39 02 5503 2141, flavio.caprioli@policlinico.mi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of Fatigue variation after 4 weeks of treatment (t4) (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05874089, which also lists 19 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2023; AzTrials last refreshed its copy on 8 Nov 2026.