Sulfureous Water Therapy in Viral Respiratory Diseases (STWandRVD)

March 2, 2024 updated by: Mario Fontana, University of Roma La Sapienza

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:

  • 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Rome
      • Tivoli, Rome, Italy, 00019
        • Acque Albule, Terme di Roma

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
Other: 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
Other Names:
  • STW aerosol
  • STW steam inhalation
Placebo Comparator: 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.
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
Other Names:
  • SDW aerosol
  • SDW steam inhalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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.
Time Frame: Day 14
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
Time Frame: Day 90
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
Time Frame: Day 1
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
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)
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
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)
Day 90

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 serum inflammatory responses prior inhalations treatment by determining IL-6, IL-1β, S100B, GSS, ACE serum concentration
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 serum inflammatory responses at 14 days since inhalations treatment start by determining IL-6, IL-1β, S100B, GSS, ACE serum concentration
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 serum inflammatory responses at 90 days since inhalations treatment start by determining IL-6, IL-1β, S100B, GSS, ACE serum concentration
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
Collection with swabs and 16SrDNA analysis of the nasopharyngeal secretions prior inhalations treatment.
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
Collection with swabs and 16S rDNA analysis of the nasopharyngeal secretions at 14 days since inhalations treatment start
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
Collection with swabs and 16S rDNA analysis of the nasopharyngeal secretions at 90 days since inhalations treatment start
Day 90

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: Day 1
Impact of post covid respiratory-related impairment on the quality of life prior treatment is evaluated using the Saint George respiratory questionnaire (SGRQ)
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
Time Frame: Day 90
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)
Day 90

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Roma La Sapienza

Collaborators

Queen Mary University of London
Università degli studi di Roma Foro Italico
Bios Prevention Srl

Investigators

  • Study Chair: Mario Fontana, Prof, MD, La Sapienza, University of Rome
  • Principal Investigator: Serena Crucianelli, MD, La Sapienza, University of Rome
  • Principal Investigator: Alessia Mariano, PhD, La Sapienza, University of Rome

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 30, 2023

Primary Completion (Actual)

August 1, 2023

Study Completion (Actual)

September 30, 2023

Study Registration Dates

First Submitted

February 9, 2024

First Submitted That Met QC Criteria

March 2, 2024

First Posted (Actual)

March 6, 2024

Study Record Updates

Last Update Posted (Actual)

March 6, 2024

Last Update Submitted That Met QC Criteria

March 2, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • acquealbuleroma1
  • AR1221816703484E (Other Grant/Funding Number: La Sapienza University, Rome, Italy)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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