RecruitingNCT05874089DELong#3Updated May 24, 2023

VSL#3® vs Placebo in the Treatment of Fatigue and Other Symptoms in Long Covid (DELong#3)

An interventional study of VSL#3® and Placebo in Long COVID, sponsored by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico. Recruiting at 1 site in Italy. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2023-05-24.

Sponsored by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico · Not applicable, Interventional, and Treatment

From the registry’s dates

Primary completion was expected by Sep 2023, 3 years 1 month ago, but the record still lists the study as recruiting.
Registered 6 months after the study started (first participant enrolled Nov 2022, registered May 2023).
Started Nov 2022; still recruiting 3 years 11 months later.

Phase: Not applicable
Study type: Interventional
Enrollment: 96
Allocation: Randomized
Ages: 18 Years to 65 Years
Sex: All

Study 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 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 studied

Long COVID

Browse trials for

Keywords

Long Covid
Fatigue
Gut Microbioma
Dysbiosis
COVID-19
Coronavirus Infections

In context

Post-Acute COVID-19 Syndrome

520 studies on the registry are indexed under Post-Acute COVID-19 Syndrome; 186 are open to participants now.

This study's planned enrollment of 96 is above the median of 60 across 361 interventional studies indexed under Post-Acute COVID-19 Syndrome.

Browse Post-Acute COVID-19 Syndrome studies →

Lead sponsor

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico is the lead sponsor of 214 studies on the registry; 71 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 65 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Study design

Phase: Not applicable
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 96 participants (estimated)

Study arms

Active comparator
VSL#3®
VSL#3® 450 billion sachets, two sachets per day (900 billion of bacteria per day) for 28 days
Dietary Supplement: VSL#3®
Placebo comparator
Placebo
Placebo sachets, two sachets per day for 28 days
Dietary Supplement: Placebo

Interventions

Dietary supplementVSL#3®
VSL#3® 450 billions/sachets
Dietary supplementPlacebo
Placebo sachets with maltose, cornstarch and dioxide
Also known as: Placebo (for VSL#3®)

What researchers measure

Primary outcomes

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)
Time frame: 4 weeks

Secondary outcomes

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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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.
Time frame: 4 weeks

Study locations

1 of 1 sites recruiting

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, MI 20122, Italy
- Beatrice Marinoni, MD · Contact · beatrice.marinoni@unimi.it · +39 02 5503 2141
Recruiting

References and documents

Publications

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Chalder 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 8463991 ↗
Ceban 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 34973396 ↗
Chen 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 33833065 ↗
Choutka 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. Erratum In: Nat Med. 2022 Aug;28(8):1723. doi: 10.1038/s41591-022-01952-7. PubMed 35585196 ↗
Davis 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. Erratum In: Nat Rev Microbiol. 2023 Jun;21(6):408. doi: 10.1038/s41579-023-00896-0. PubMed 36639608 ↗
Farsi 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 35310853 ↗
Fernandez-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 36378309 ↗
Giannos 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 35233795 ↗
Global 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 36215063 ↗
Guo 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 36758522 ↗
Li 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 31333675 ↗
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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. PubMed 32442562 ↗

Study documents

Protocol and statistical analysis plan · May 14, 2022
Informed consent form · May 15, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Undecided

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on May 24, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT05874089
Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Responsible party: Flavio Caprioli (Associate Professor of Gastroenterology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico) — Principal investigator
First posted: May 24, 2023
Start date: Nov 3, 2022
Primary completion: Sep 3, 2023 (estimated)
Completion: Nov 3, 2023 (estimated)
Last update: May 24, 2023

Study contacts

Flavio Caprioli, MD, PhD

Contact

flavio.caprioli@policlinico.mi.it

+39 02 5503 2141

Beatrice Marinoni, MD

Contact

beatrice.marinoni@unimi.it

+39 02 5503 2141

Flavio Caprioli, MD, PhD

study director · Fondazione IRCCS Cà Granda, Ospedale Policlinico di Milano

Oversight

FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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