Ignite Creation Date:
2025-12-24 @ 11:38 PM
Ignite Modification Date:
2025-12-25 @ 9:28 PM
Study NCT ID:
NCT06294756
Status:
COMPLETED
Last Update Posted:
2024-03-06
First Post:
2024-02-09
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Sulfureous Water Therapy in Viral Respiratory Diseases
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000094024', 'term': 'Post-Acute COVID-19 Syndrome'}], 'ancestors': [{'id': 'D000086382', 'term': 'COVID-19'}, {'id': 'D011024', 'term': 'Pneumonia, Viral'}, {'id': 'D011014', 'term': 'Pneumonia'}, {'id': 'D012141', 'term': 'Respiratory Tract Infections'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D018352', 'term': 'Coronavirus Infections'}, {'id': 'D003333', 'term': 'Coronaviridae Infections'}, {'id': 'D030341', 'term': 'Nidovirales Infections'}, {'id': 'D012327', 'term': 'RNA Virus Infections'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D000094025', 'term': 'Post-Infectious Disorders'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR'], 'maskingDescription': "Neither the participants nor any of the medical researchers or laboratory staff involved in the screening, enrolment, clinical evaluation, monitoring, and laboratory as well as statistics of the participant's analyses were aware of the study intervention received (STW vs SDW). A randomization list (1:1 active vs placebo) was created prior to recruiting. The inhalation assistant randomized the participant according to the list and administered the intervention. Therefore, the inhalation assistant was unblinded to the treatment assigned but blinded to the medical condition of the participants."}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'The study is a double-blind, interventional, randomized case-control, pilot trial assessing the efficacy of sulfureous thermal water (STW) inhalations in patients diagnosed with long-COVID. The eligible subjects were randomized in a 1:1 ratio to either: active (STW) or placebo (SDW) group for the inhalation therapy and tested at 3 timepoints: Visit 1 (prior treatment), Visit 2 (just after treatment) , Visit 3 (3 months after treatment).'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 30}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2023-05-30', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-03', 'completionDateStruct': {'date': '2023-09-30', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-03-02', 'studyFirstSubmitDate': '2024-02-09', 'studyFirstSubmitQcDate': '2024-03-02', 'lastUpdatePostDateStruct': {'date': '2024-03-06', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2024-03-06', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2023-08-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'to assess whether thermal water inhalation determine changes in the perceived impact of respiratory related impairment on the quality of life (Qol) through a validate Saint George respiratory questionnaire', 'timeFrame': 'Day 1', 'description': 'Impact of post covid respiratory-related impairment on the quality of life prior treatment is evaluated using the Saint George respiratory questionnaire (SGRQ)'}, {'measure': 'to assess whether thermal water inhalation determine changes in the perceived impact of respiratory related impairment on the quality of life (Qol) through a validate Saint George respiratory questionnaire', 'timeFrame': 'Day 90', 'description': '90 days after treatment Impact of post covid respiratory-related impairment on the quality of life is evaluated using the Saint George respiratory questionnaire (SGRQ)'}], 'primaryOutcomes': [{'measure': 'To determine whether Sulfurous Thermal water (STW) inhalations may have effects on post covid-pulmonary sequelae assessing changes in pulmonar functionality through spirometric parameters.', 'timeFrame': 'Day1', 'description': 'To assess the prior treatment whole pulmonary functionality by spirometry and DLCO spirometry'}, {'measure': 'To determine whether Sulfurous Thermal water (STW) inhalations may have effects on post covid-pulmonary sequelae assessing changes in pulmonar functionality through spirometric parameters.', 'timeFrame': 'Day 14', 'description': 'To assess the whole pulmonary functionality at 14 days since inhalations start by spirometry and DLCO spirometry'}, {'measure': 'To determine whether Sulfurous Thermal water (STW) inhalations may have effects on post covid-pulmonary sequelae assessing changes in pulmonar functionality through spirometric parameters', 'timeFrame': 'Day 90', 'description': 'To assess the whole pulmonary functionality at 90 days since inhalations start by spirometry and DLCO spirometry.'}, {'measure': 'To determine whether Sulfurous Thermal water (STW) inhalations can improve the cardiopulmonary response to physical exertion measured as SpO2, Heart rate, Borg score and traversed meters in patients affected by long COVID', 'timeFrame': 'Day 1', 'description': 'To assess the cardiopulmonary response to physical exertion prior inhalations therapy with the six minutes walking test (6MWT)'}, {'measure': 'To determine whether Sulfurous Thermal water (STW) inhalations can improve the cardiopulmonary response to physical exertion measured as SpO2, Heart rate, Borg score and traversed meters in patients affected by long COVID', 'timeFrame': 'Day 14', 'description': 'To assess the cardiopulmonary response involved during physical exertion at 14 days since inhalations start with the six minutes walking test (6MWT)'}, {'measure': 'To determine whether Sulfurous Thermal water (STW) inhalations can improve the cardiopulmonary response to physical exertion measured as SpO2, Heart rate, Borg score and traversed meters in patients affected by long COVID', 'timeFrame': 'Day 90', 'description': 'To assess the cardiopulmonary response to physical exertion at 90 days since inhalations start with the six minutes walking test (6MWT)'}], 'secondaryOutcomes': [{'measure': 'To assess if H2S present in STW can interfere with concentration of inflammatory markers ( as IL1B, IL-6, ACE, S100B, GSS, Hs-CRP) typically alterated in long covid patients.', 'timeFrame': 'Day 1', 'description': 'To assess serum inflammatory responses prior inhalations treatment by determining IL-6, IL-1β, S100B, GSS, ACE serum concentration'}, {'measure': 'To assess if H2S present in STW can interfere with concentration of inflammatory markers ( as IL1B, IL-6, ACE, S100B, GSS, Hs-CRP) typically alterated in long covid patients.', 'timeFrame': 'Day 14', 'description': 'To assess serum inflammatory responses at 14 days since inhalations treatment start by determining IL-6, IL-1β, S100B, GSS, ACE serum concentration'}, {'measure': 'To assess if H2S present in STW can interfere with concentration of inflammatory markers ( as IL1B, IL-6, ACE, S100B, GSS, Hs-CRP) typically alterated in long covid patients.', 'timeFrame': 'Day 90', 'description': 'To assess serum inflammatory responses at 90 days since inhalations treatment start by determining IL-6, IL-1β, S100B, GSS, ACE serum concentration'}, {'measure': 'to assess whether thermal water inhalation with sulfurous water may determine qualitative and quantitative changes of the nasal microbiome by assessing alpha and beta diversity after nasal sample collection', 'timeFrame': 'Day 1', 'description': 'Collection with swabs and 16SrDNA analysis of the nasopharyngeal secretions prior inhalations treatment.'}, {'measure': 'to assess whether thermal water inhalation with sulfurous water may determine qualitative and quantitative changes of the nasal microbiome by assessing alpha and beta diversity after nasal sample collection', 'timeFrame': 'Day 14', 'description': 'Collection with swabs and 16S rDNA analysis of the nasopharyngeal secretions at 14 days since inhalations treatment start'}, {'measure': 'to assess whether thermal water inhalation with sulfurous water may determine qualitative and quantitative changes of the nasal microbiome by assessing alpha and beta diversity after nasal sample collection', 'timeFrame': 'Day 90', 'description': 'Collection with swabs and 16S rDNA analysis of the nasopharyngeal secretions at 90 days since inhalations treatment start'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['LONG-COVID', 'spa', 'Inhalation therapy', 'Sulfurous thermal water', 'H2S', 'Nasal microbiome'], 'conditions': ['Long-COVID', 'Post COVID-19 Condition', 'Chronic COVID-19 Syndrome', 'Post Acute Sequelae of COVID-19']}, 'referencesModule': {'references': [{'pmid': '38193730', 'type': 'BACKGROUND', 'citation': 'Fowora MA, Aiyedogbon A, Omolopo I, Tajudeen AO, Olanlege A-L, Abioye A, Akintunde GB, Salako BL. Effect of nasal carriage of Bacillus species on COVID-19 severity: a cross-sectional study. Microbiol Spectr. 2024 Feb 6;12(2):e0184323. doi: 10.1128/spectrum.01843-23. Epub 2024 Jan 9.'}, {'pmid': '36639608', 'type': 'RESULT', 'citation': '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.'}, {'pmid': '36685609', 'type': 'RESULT', 'citation': 'Huerne K, Filion KB, Grad R, Ernst P, Gershon AS, Eisenberg MJ. Epidemiological and clinical perspectives of long COVID syndrome. Am J Med Open. 2023 Jun;9:100033. doi: 10.1016/j.ajmo.2023.100033. Epub 2023 Jan 18.'}, {'pmid': '37064029', 'type': 'RESULT', 'citation': 'Low RN, Low RJ, Akrami A. A review of cytokine-based pathophysiology of Long COVID symptoms. Front Med (Lausanne). 2023 Mar 31;10:1011936. doi: 10.3389/fmed.2023.1011936. eCollection 2023.'}, {'pmid': '36662879', 'type': 'RESULT', 'citation': 'Ribeiro Carvalho CR, Lamas CA, Chate RC, Salge JM, Sawamura MVY, de Albuquerque ALP, Toufen Junior C, Lima DM, Garcia ML, Scudeller PG, Nomura CH, Gutierrez MA, Baldi BG; HCFMUSP Covid-19 Study Group. Long-term respiratory follow-up of ICU hospitalized COVID-19 patients: Prospective cohort study. PLoS One. 2023 Jan 20;18(1):e0280567. doi: 10.1371/journal.pone.0280567. eCollection 2023.'}, {'pmid': '34273080', 'type': 'RESULT', 'citation': 'Maccarone MC, Masiero S. Spa therapy interventions for post respiratory rehabilitation in COVID-19 subjects: does the review of recent evidence suggest a role? Environ Sci Pollut Res Int. 2021 Sep;28(33):46063-46066. doi: 10.1007/s11356-021-15443-8. Epub 2021 Jul 17.'}, {'pmid': '28106111', 'type': 'RESULT', 'citation': 'Bazhanov N, Escaffre O, Freiberg AN, Garofalo RP, Casola A. Broad-Range Antiviral Activity of Hydrogen Sulfide Against Highly Pathogenic RNA Viruses. Sci Rep. 2017 Jan 20;7:41029. doi: 10.1038/srep41029.'}, {'pmid': '32710297', 'type': 'RESULT', 'citation': 'Antonelli M, Donelli D. Respiratory rehabilitation for post-COVID19 patients in spa centers: first steps from theory to practice. Int J Biometeorol. 2020 Oct;64(10):1811-1813. doi: 10.1007/s00484-020-01962-5. Epub 2020 Jul 24.'}, {'pmid': '36195943', 'type': 'RESULT', 'citation': 'Merenstein C, Bushman FD, Collman RG. Alterations in the respiratory tract microbiome in COVID-19: current observations and potential significance. Microbiome. 2022 Oct 5;10(1):165. doi: 10.1186/s40168-022-01342-8.'}], 'seeAlsoLinks': [{'url': 'https://www.termediroma.org/pdf/analisi-chimico-fisico-2018.pdf', 'label': 'Chemical composition of STW: Acque Albule, Terme di Roma'}]}, 'descriptionModule': {'briefSummary': 'The goal of this double-blind, interventional, randomized case-control, pilot trial is to evaluate the effects of active sulfurous (STW) versus placebo (SDW) inhalations on blood test parameters, serum inflammatory cytokines, spirometry data, as well as qualitative and quantitative changes in the nasal microbiome of subjects affected by long Covid.\n\nThe main questions it aims to answer are:\n\n* if STW inhalations are effective on respiratory issues due to long covid compared to the placebo inhalation (SDW)\n* if STW inhalations are effective on long covid related fatigue issues compared to the placebo inhalation (SDW)\n* if H2S inhaled with STW is effective in modulating (decreasing) cytokines which are related to long covid cytokine storm compared to placebo inhalation with no H2S (SDW)\n* if STW inhalation modify nasal microbiome both from a qualitative and quantitative point of view respect to placebo inhalation (SDW) Participants will be randomly assigned to active inhalations (STW) or placebo inhalations (SDW) arm and subjected to 12 consecutive sessions of 20 minutes.\n\nBoth arms will be tested for:\n\n* cytokines and inflammatory markers concentration (IL1b, IL6, ACE, GSS, S100B, Hs-CRP)\n* spirometry (resting, forced, DLCO)\n* exertion response (6 minutes walking test)\n* nasal microbiome sampling at visit 1 (enrolment), at visit 2(right after the inhalation treatment) and at visit 3 (3 months after treatment).\n\nResearchers will compare results reported by STW to those of SDW group to see if significative differences are detectable.', 'detailedDescription': "The study is a double-blind, interventional, randomized case-control, pilot trial assessing the efficacy of sulfureous thermal water (STW) inhalations in patients diagnosed with long-COVID. The study was performed from May to October 2023 at the Acque Albule spa facility, Terme di Roma, Tivoli Terme, Rome, Italy. The SPA-center rehab program included 12 consecutive sessions for 20 minutes each from day 1 for 12 days. Re-assessment of study analyses was performed on day 14 after (Visit 2). The follow-up (Visit 3) was 90 days after Visit 1.\n\nEligible subjects were adult outpatients, presenting to the spa facility with an independent prescription of inhalation therapy with sulfurous water for post-COVID respiratory issues. The participants had previously tested positive in certified PCR screening for SARS-Cov-2 infection (data from the Regional Archive of Health Service for SARS-Cov-2 Infection) and, at the time of the study, had a positive diagnosis of long-COVID syndrome with pulmonary involvement.\n\nNeither the participants nor any of the medical researchers or laboratory staff involved in the screening, enrolment, clinical evaluation, monitoring, and laboratory as well as statistics of the participant's analyses were aware of the study intervention received (STW vs SDW). A randomization list (1:1 active vs placebo) was created prior to recruiting. The inhalation assistant randomized the participant according to the list and administered the intervention. Therefore, the inhalation assistant was unblinded to the treatment assigned but blinded to the medical condition of the participants.\n\nAt each session of treatment delivered at Visit 1 and Visit 2, participants were tested for SARS-Cov-2 infection, underwent resting plus forced spirometry and alveolar-capillary diffusion of carbon monoxide (DLCO) spirometry, and performed the the six minutes walking test (6MWT). St George Respiratory Questionnaire (SGQ) used to determine the impact of pulmonary impairment on the quality of life was completed at Visit 1 and Visit 3, patient satisfaction survey was submitted to participants at Visit 3 only. Moreover, blood samples for routine analysis, urine sample collections, and nasal swabs for microbiome sampling were collected at each visit. At the end of Visit 1 (screening/enrolment day), the eligible subjects were randomized in a 1:1 ratio to either: active (STW) or placebo (SDW) group for the inhalation therapy. Both active and controls underwent inhalation therapy once a day for 12 days (from day 1)."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* · Adults aged from 18 to 75.\n\n * Willing and capable of giving informed consent.\n * Participants with smoking habits or not\n * Participants with COVID vaccination or not\n * Negative to Sars-Cov2 rapid swabs at screening visit\n * Certified previous Sars Cov2 infection (Regional Public Health Service archives of Sars Cov2 infection)\n * Certified diagnosis of long COVID (post-infective onset symptoms only, lasting more than 4 months since swab negativisation).\n * Any severity of Covid symptoms during acute infection (Home care, ICU admission, ventilation)\n * Participants treated with inhaled bronchodilators or not.\n * Willing and able to comply with scheduled visits, laboratory tests, and other study procedures.\n\nExclusion Criteria:\n\n* · Obesity (BMI\\>32).\n\n * Walking impairment.\n * Pre-existing other comorbidities affecting the airways (e.g., asthma, rhinitis, etc.).\n * Therapy with inhaled, IV, or IM steroids.\n * Pre-existing diagnosis of depression, psychological or psychiatric disorders.\n * Patients currently recruited to other clinical trials.'}, 'identificationModule': {'nctId': 'NCT06294756', 'acronym': 'STWandRVD', 'briefTitle': 'Sulfureous Water Therapy in Viral Respiratory Diseases', 'organization': {'class': 'OTHER', 'fullName': 'University of Roma La Sapienza'}, 'officialTitle': 'Effects of Sulfurous Thermal Waters Inhalations on Long-COVID Syndrome: a Double-blinded, Interventional, Randomized Case-control, Pilot Study on a Spa Centered Rehab Program', 'orgStudyIdInfo': {'id': 'acquealbuleroma1'}, 'secondaryIdInfos': [{'id': 'AR1221816703484E', 'type': 'OTHER_GRANT', 'domain': 'La Sapienza University, Rome, Italy'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Long covid patients undergoing inhalations with sulfurous thermal water (STW)', 'description': 'Adult Outpatients aged 18-75, presenting to the spa facility with an independent prescription of inhalation therapy with sulfurous water for post-COVID respiratory issues.\n\nActive arm treatment consisted of 12 consecutive sessions of sulfurous thermal water (STW) from Visit 1 for 12 days.\n\nRe-assessment of study analyses was performed on Visit 2 after, 14 days from Visit 1. The follow-up (Visit 3) was 90 days after Visit 1.', 'interventionNames': ['Other: Inhalation of Sulfurous Thermal Water']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Long covid patients undergoing inhalations with Sterile Distilled non-pyrogenic Water (SDW)', 'description': 'Adult Outpatients aged 18-75, presenting to the spa facility with an independent prescription of inhalation therapy with sulfurous water for post-COVID respiratory issues. Placebo arm treatment consisted of 12 consecutive sessions of Sterile Distilled non-pyrogenic Water (SDW) from Visit 1 for 12 days.\n\nRe-assessment of study analyses was performed on Visit 2 after, 14 days from Visit 1. The follow-up (Visit 3) was 90 days after Visit 1.', 'interventionNames': ['Other: Inhalation of Sterile Distilled non-pyrogenic Water']}], 'interventions': [{'name': 'Inhalation of Sulfurous Thermal Water', 'type': 'OTHER', 'otherNames': ['STW aerosol', 'STW steam inhalation'], 'description': 'Active Inhalation protocol based on 12 consecutive sessions, 20 minutes each, once a day from Visit 1 through a conventional thermal water aerosolization Faset™system (Faset Spa, Trezzano sul Naviglio, Milan, Italy) delivering particles of TW with a diameter between 0.6 µm \\<MMAD \\< 5 µm. Treatment consisted of 10 minutes of warm steam and 10 minutes of aerosol inhalation with nasal prongs.', 'armGroupLabels': ['Long covid patients undergoing inhalations with sulfurous thermal water (STW)']}, {'name': 'Inhalation of Sterile Distilled non-pyrogenic Water', 'type': 'OTHER', 'otherNames': ['SDW aerosol', 'SDW steam inhalation'], 'description': 'Placebo Inhalation protocol based on 12 consecutive sessions, 20 minutes each, once a day from Visit 1 through a modified thermal water aerosolization Faset™system, previously disconnected from the hydraulic circuit that supplied TW and connected to non-pyrogenic sterile water reservoirs (Highly depurated water- Pharmaceutical grade FU-for external and internal use, Makeitlab, Canosa di Puglia, BT, Italy). Treatment consisted of 10 minutes of warm steam and 10 minutes of aerosol inhalation with nasal prongs delivering particles of SDW with a diameter between 0.6 µm \\<MMAD \\< 5 µm.', 'armGroupLabels': ['Long covid patients undergoing inhalations with Sterile Distilled non-pyrogenic Water (SDW)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '00019', 'city': 'Tivoli', 'state': 'Rome', 'country': 'Italy', 'facility': 'Acque Albule, Terme di Roma', 'geoPoint': {'lat': 41.95952, 'lon': 12.8016}}], 'overallOfficials': [{'name': 'Mario Fontana, Prof, MD', 'role': 'STUDY_CHAIR', 'affiliation': 'La Sapienza, University of Rome'}, {'name': 'Serena Crucianelli, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'La Sapienza, University of Rome'}, {'name': 'Alessia Mariano, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'La Sapienza, University of Rome'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Roma La Sapienza', 'class': 'OTHER'}, 'collaborators': [{'name': 'Università degli studi di Roma Foro Italico', 'class': 'OTHER'}, {'name': 'Queen Mary University of London', 'class': 'OTHER'}, {'name': 'Bios Prevention Srl', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Associate Professor of Biochemistry, Resident physician', 'investigatorFullName': 'Mario Fontana', 'investigatorAffiliation': 'University of Roma La Sapienza'}}}}