Sulfureous Water Therapy in Viral Respiratory Diseases

NCT06294756 | Completed

• 2 other identifiers: acquealbuleroma1AR1221816703484E
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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 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.

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

Outcome Measures

Primary Outcomes (6)

• 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

  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

  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.

  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)

  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)

  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)

  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.

  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.

  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.

  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

  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

  Day 14

Other Outcomes (2)

• 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

  Day 1

• 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

  Day 90

Study Arms (2)

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.

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.

Other: Inhalation of Sterile Distilled non-pyrogenic Water

Interventions

Inhalation of Sulfurous Thermal Water 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.

Also known as: STW aerosol, STW steam inhalation

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

Inhalation of Sterile Distilled non-pyrogenic Water 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.

Also known as: SDW aerosol, SDW steam inhalation

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

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• · 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.

You may not qualify if:

• · 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.

Sponsors & Collaborators

• University of Roma La Sapienza: lead
• Università degli studi di Roma Foro Italico: collaborator
• Queen Mary University of London: collaborator
• Bios Prevention Srl: collaborator

Study Sites (1)

Acque Albule, Terme di Roma

Tivoli, Rome, 00019, Italy

Location

Related Publications (9)

• 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: 38193730 BACKGROUND

• 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: 36639608 RESULT

• 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: 36685609 RESULT

• 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: 37064029 RESULT

• 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: 36662879 RESULT

• 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: 34273080 RESULT

• 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: 28106111 RESULT

• 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: 32710297 RESULT

• 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.

  PMID: 36195943 RESULT

Related Links

• Chemical composition of STW: Acque Albule, Terme di Roma

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Mario Fontana, Prof, MD

  La Sapienza, University of Rome

  STUDY CHAIR

• Serena Crucianelli, MD

  La Sapienza, University of Rome

  PRINCIPAL INVESTIGATOR

• Alessia Mariano, PhD

  La Sapienza, University of Rome

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Biochemistry, Resident physician

Model Details: 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).

Study Record Dates

• First Submitted: February 9, 2024
• First Posted: March 6, 2024
• Study Start: May 30, 2023
• Primary Completion: August 1, 2023
• Study Completion: September 30, 2023
• Last Updated: March 6, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)