Long-COVIDSTWandRVDNCT06294756
Sulfureous Water Therapy in Viral Respiratory Diseases
A study testing Inhalation of Sulfurous Thermal Water and Inhalation of Sterile Distilled non-pyrogenic Water in people with Long-COVID and Post COVID-19 Condition, run by University of Roma La Sapienza at 1 site in Italy.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Long-COVID, Post COVID-19 Condition, Chronic COVID-19 Syndrome
- What is being tested?
- Inhalation of Sulfurous Thermal Water and Inhalation of Sterile Distilled non-pyrogenic Water
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- 30 May 2023to 30 Sep 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- · Adults aged from 18 to 75.
- Willing and capable of giving informed consent.
- Participants with smoking habits or not
- Participants with COVID vaccination or not
- Negative to Sars-Cov2 rapid swabs at screening visit
- Certified previous Sars Cov2 infection (Regional Public Health Service archives of Sars Cov2 infection)
Show all 10Show fewer
- Certified diagnosis of long COVID (post-infective onset symptoms only, lasting more than 4 months since swab negativisation).
- Any severity of Covid symptoms during acute infection (Home care, ICU admission, ventilation)
- Participants treated with inhaled bronchodilators or not.
- Willing and able to comply with scheduled visits, laboratory tests, and other study procedures.
Who cannot join
- · Obesity (BMI>32).
- Walking impairment.
- Pre-existing other comorbidities affecting the airways (e.g., asthma, rhinitis, etc.).
- Therapy with inhaled, IV, or IM steroids.
- Pre-existing diagnosis of depression, psychological or psychiatric disorders.
- Patients currently recruited to other clinical trials.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
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.
The main questions it aims to answer are:
Read more
- if STW inhalations are effective on respiratory issues due to long covid compared to the placebo inhalation (SDW)
- if STW inhalations are effective on long covid related fatigue issues compared to the placebo inhalation (SDW)
- 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)
- 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.
Both arms will be tested for:
- cytokines and inflammatory markers concentration (IL1b, IL6, ACE, GSS, S100B, Hs-CRP)
- spirometry (resting, forced, DLCO)
- exertion response (6 minutes walking test)
- nasal microbiome sampling at visit 1 (enrolment), at visit 2(right after the inhalation treatment) and at visit 3 (3 months after treatment).
Researchers will compare results reported by STW to those of SDW group to see if significative differences are detectable.
Read the detailed description
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.
Eligible 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.
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.
At 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).
- Conditions
- Long-COVID, Post COVID-19 Condition, Chronic COVID-19 Syndrome, Post Acute Sequelae of COVID-19
- Being tested
- Inhalation of Sulfurous Thermal Water, Inhalation of Sterile Distilled non-pyrogenic Water
- Keywords
- LONG-COVID, spa, Inhalation therapy, Sulfurous thermal water, H2S, Nasal microbiome
- Medical subject headings
- Post-Acute COVID-19 Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inhalation of Sulfurous Thermal WaterOther
Also called STW aerosol, STW steam inhalation
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.
Inhalation of Sterile Distilled non-pyrogenic WaterOther
Also called SDW aerosol, SDW steam inhalation
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.
| Study group | Role | What they receive |
|---|---|---|
| Long covid patients undergoing inhalations with sulfurous thermal water (STW) | Active comparator | 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.
Active arm treatment consisted of 12 consecutive sessions of sulfurous thermal water (STW) from Visit 1 for 12 days.
Re-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. Receives: Other: Inhalation of Sulfurous Thermal Water |
| Long covid patients undergoing inhalations with Sterile Distilled non-pyrogenic Water (SDW) | Placebo comparator | 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.
Re-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. Receives: Other: Inhalation of Sterile Distilled non-pyrogenic Water |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine whether Sulfurous Thermal water (STW) inhalations may have effects on post covid-pulmonary sequelae assessing changes in pulmonar functionality through spirometric parameters.
To assess the prior treatment whole pulmonary functionality by spirometry and DLCO spirometry
Measured: Day1
To determine whether Sulfurous Thermal water (STW) inhalations may have effects on post covid-pulmonary sequelae assessing changes in pulmonar functionality through spirometric parameters.
To assess the whole pulmonary functionality at 14 days since inhalations start by spirometry and DLCO spirometry
Measured: Day 14
To determine whether Sulfurous Thermal water (STW) inhalations may have effects on post covid-pulmonary sequelae assessing changes in pulmonar functionality through spirometric parameters
To assess the whole pulmonary functionality at 90 days since inhalations start by spirometry and DLCO spirometry.
Measured: Day 90
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
To assess the cardiopulmonary response to physical exertion prior inhalations therapy with the six minutes walking test (6MWT)
Measured: Day 1
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
To assess the cardiopulmonary response involved during physical exertion at 14 days since inhalations start with the six minutes walking test (6MWT)
Measured: Day 14
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
To assess the cardiopulmonary response to physical exertion at 90 days since inhalations start with the six minutes walking test (6MWT)
Measured: Day 90
Secondary outcomes (6)
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.
To assess serum inflammatory responses prior inhalations treatment by determining IL-6, IL-1β, S100B, GSS, ACE serum concentration
Measured: Day 1
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.
To assess serum inflammatory responses at 14 days since inhalations treatment start by determining IL-6, IL-1β, S100B, GSS, ACE serum concentration
Measured: Day 14
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.
To assess serum inflammatory responses at 90 days since inhalations treatment start by determining IL-6, IL-1β, S100B, GSS, ACE serum concentration
Measured: Day 90
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
Collection with swabs and 16SrDNA analysis of the nasopharyngeal secretions prior inhalations treatment.
Measured: Day 1
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
Collection with swabs and 16S rDNA analysis of the nasopharyngeal secretions at 14 days since inhalations treatment start
Measured: Day 14
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
Collection with swabs and 16S rDNA analysis of the nasopharyngeal secretions at 90 days since inhalations treatment start
Measured: Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2024
- Study start30 May 2023
- Primary completion1 Aug 2023
- Study completion30 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)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 University of Roma La SapienzaThe 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
- 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).
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Roma La Sapienza
- Sponsor type
- University, hospital or other
- Collaborators
- Università degli studi di Roma Foro Italico, Queen Mary University of London, Bios Prevention Srl
- Responsible party
- Principal investigator, Mario Fontana, University of Roma La Sapienza
- Investigators
- Mario Fontana, Prof, MD, Study chair, La Sapienza, University of RomeSerena Crucianelli, MD, Principal investigator, La Sapienza, University of RomeAlessia Mariano, PhD, Principal investigator, La Sapienza, University of Rome
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06294756
- Sponsor's protocol ID
- acquealbuleroma1
- Other IDs
- AR1221816703484E
- Acronym
- STWandRVD
- Status last verified
- Mar 2024
- First submitted
- 9 Feb 2024
- Last updated
- 6 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38193730Davis 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 36639608Huerne 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.
PubMed 36685609Low 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.
PubMed 37064029Ribeiro 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.
PubMed 36662879Maccarone 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.
PubMed 34273080Bazhanov 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.
PubMed 28106111Antonelli 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.
PubMed 32710297Merenstein 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.
PubMed 36195943
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06294756
- Acronym / sponsor ID
- STWandRVD / acquealbuleroma1
- Conditions
- Long-COVID, Post COVID-19 Condition, Chronic COVID-19 Syndrome, Post Acute Sequelae of COVID-19
- Keywords
- LONG-COVID, spa, Inhalation therapy, Sulfurous thermal water, H2S, Nasal microbiome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of Roma La SapienzaUniversity, hospital or other
- Collaborators
- Università degli studi di Roma Foro Italico, Queen Mary University of London, Bios Prevention Srl
- Study start
- 30 May 2023 (actual)
- Primary completion
- 1 Aug 2023 (actual)
- Study completion
- 30 Sep 2023 (actual)
- First posted
- 6 Mar 2024 (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.
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.
The main questions it aims to answer are:
- if STW inhalations are effective on respiratory issues due to long covid compared to the placebo inhalation (SDW)
- if STW inhalations are effective on long covid related fatigue issues compared to the placebo inhalation (SDW)
- 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)
- 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.
Both arms will be tested for:
- cytokines and inflammatory markers concentration (IL1b, IL6, ACE, GSS, S100B, Hs-CRP)
- spirometry (resting, forced, DLCO)
- exertion response (6 minutes walking test)
- nasal microbiome sampling at visit 1 (enrolment), at visit 2(right after the inhalation treatment) and at visit 3 (3 months after treatment).
Researchers will compare results reported by STW to those of SDW group to see if significative differences are detectable.
Detailed description
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.
Eligible 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.
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.
At 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| Long covid patients undergoing inhalations with sulfurous thermal water (STW) | Active comparator | Other: Inhalation of Sulfurous Thermal WaterAdult Outpatients aged 18-75, presenting to the spa facility with an independent prescription of inhalation therapy with sulfurous water for post-COVID respiratory issues. Active arm treatment consisted of 12 consecutive sessions of sulfurous thermal water (STW) from Visit 1 for 12 days. Re-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. |
| Long covid patients undergoing inhalations with Sterile Distilled non-pyrogenic Water (SDW) | Placebo comparator | Other: Inhalation of Sterile Distilled non-pyrogenic WaterAdult 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. Re-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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- · Adults aged from 18 to 75.
Key exclusion criteria (6 listed)
- · Obesity (BMI>32).
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 |
|---|---|---|
| Inhalation of Sulfurous Thermal WaterAlso: STW aerosol, STW steam inhalationActive 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. | Other | Long covid patients undergoing inhalations with sulfurous thermal water (STW) |
| Inhalation of Sterile Distilled non-pyrogenic WaterAlso: SDW aerosol, SDW steam inhalationPlacebo 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. | Other | Long covid patients undergoing inhalations with Sterile Distilled non-pyrogenic Water (SDW) |
Primary outcome
To determine whether Sulfurous Thermal water (STW) inhalations may have effects on post covid-pulmonary sequelae assessing changes in pulmonar functionality through spirometric parameters.
Time frame: Day1
To assess the prior treatment whole pulmonary functionality by spirometry and DLCO spirometry
To determine whether Sulfurous Thermal water (STW) inhalations may have effects on post covid-pulmonary sequelae assessing changes in pulmonar functionality through spirometric parameters.
Time frame: Day 14
To assess the whole pulmonary functionality at 14 days since inhalations start by spirometry and DLCO spirometry
To determine whether Sulfurous Thermal water (STW) inhalations may have effects on post covid-pulmonary sequelae assessing changes in pulmonar functionality through spirometric parameters
Time frame: Day 90
To assess the whole pulmonary functionality at 90 days since inhalations start by spirometry and DLCO spirometry.
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
Time frame: Day 1
To assess the cardiopulmonary response to physical exertion prior inhalations therapy with the six minutes walking test (6MWT)
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
Time frame: Day 14
To assess the cardiopulmonary response involved during physical exertion at 14 days since inhalations start with the six minutes walking test (6MWT)
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
Time frame: Day 90
To assess the cardiopulmonary response to physical exertion at 90 days since inhalations start with the six minutes walking test (6MWT)
6 secondary outcomes
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.
Time frame: Day 1
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.
Time frame: Day 14
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.
Time frame: Day 90
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
Time frame: Day 1
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
Time frame: Day 14
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
Time frame: Day 90
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2024.
- Background: PubMed 38193730Fowora 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.
- Results publication: PubMed 36639608Davis 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.
- Results publication: PubMed 36685609Huerne 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.
- Results publication: PubMed 37064029Low 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.
- Results publication: PubMed 36662879Ribeiro 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.
- Results publication: PubMed 34273080Maccarone 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.
- Results publication: PubMed 28106111Bazhanov 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.
- Results publication: PubMed 32710297Antonelli 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.
- Results publication: PubMed 36195943Merenstein 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.
- Chemical composition of STW: Acque Albule, Terme di RomaLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Mario Fontana, Prof, MD study chair
La Sapienza, University of Rome
Serena Crucianelli, MD principal investigator
La Sapienza, University of Rome
Alessia Mariano, PhD principal investigator
La Sapienza, University of Rome
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Inhalation of Sulfurous Thermal Water and Inhalation of Sterile Distilled non-pyrogenic Water in people with Long-COVID and Post COVID-19 Condition, run by University of Roma La Sapienza 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 10 inclusion and 6 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: finished, as of the sponsor's last update on 6 Mar 2024. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: Day1). The study lists 6 primary outcomes in all. 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 NCT06294756, which also lists 9 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 6 Mar 2024.