Sulfureous Water Therapy in Viral Respiratory Diseases

NCT ID: NCT06294756

Last Updated: 2024-03-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-05-30

Study Completion Date

2023-09-30

Brief Summary

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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

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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

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Long-COVID Post COVID-19 Condition Chronic COVID-19 Syndrome Post Acute Sequelae of COVID-19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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).
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
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.

Study Groups

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Long covid patients undergoing inhalations with sulfurous thermal water (STW)

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.

Group Type ACTIVE_COMPARATOR

Inhalation of Sulfurous Thermal Water

Intervention Type OTHER

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.

Long covid patients undergoing inhalations with Sterile Distilled non-pyrogenic Water (SDW)

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.

Group Type PLACEBO_COMPARATOR

Inhalation of Sterile Distilled non-pyrogenic Water

Intervention Type OTHER

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.

Interventions

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Inhalation of Sulfurous Thermal Water

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.

Intervention Type OTHER

Inhalation of Sterile Distilled non-pyrogenic Water

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.

Intervention Type OTHER

Other Intervention Names

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STW aerosol STW steam inhalation SDW aerosol SDW steam inhalation

Eligibility Criteria

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Inclusion Criteria

* · 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)
* 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.

Exclusion Criteria

* · 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Università degli studi di Roma Foro Italico

OTHER

Sponsor Role collaborator

Queen Mary University of London

OTHER

Sponsor Role collaborator

Bios Prevention Srl

UNKNOWN

Sponsor Role collaborator

University of Roma La Sapienza

OTHER

Sponsor Role lead

Responsible Party

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Mario Fontana

Associate Professor of Biochemistry, Resident physician

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Mario Fontana, Prof, MD

Role: STUDY_CHAIR

La Sapienza, University of Rome

Serena Crucianelli, MD

Role: PRINCIPAL_INVESTIGATOR

La Sapienza, University of Rome

Alessia Mariano, PhD

Role: PRINCIPAL_INVESTIGATOR

La Sapienza, University of Rome

Locations

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Acque Albule, Terme di Roma

Tivoli, Rome, Italy

Site Status

Countries

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Italy

References

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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.

Reference Type BACKGROUND
PMID: 38193730 (View on PubMed)

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.

Reference Type RESULT
PMID: 36639608 (View on PubMed)

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.

Reference Type RESULT
PMID: 36685609 (View on PubMed)

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.

Reference Type RESULT
PMID: 37064029 (View on PubMed)

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.

Reference Type RESULT
PMID: 36662879 (View on PubMed)

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.

Reference Type RESULT
PMID: 34273080 (View on PubMed)

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.

Reference Type RESULT
PMID: 28106111 (View on PubMed)

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.

Reference Type RESULT
PMID: 32710297 (View on PubMed)

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.

Reference Type RESULT
PMID: 36195943 (View on PubMed)

Related Links

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https://www.termediroma.org/pdf/analisi-chimico-fisico-2018.pdf

Chemical composition of STW: Acque Albule, Terme di Roma

Other Identifiers

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AR1221816703484E

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

acquealbuleroma1

Identifier Type: -

Identifier Source: org_study_id

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