Clinical trial NCT06294756: Sulfureous Water Therapy in Viral Respiratory Diseases
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
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
Lead sponsor: University of Roma La Sapienza
Sponsor class: OTHER
Collaborators: name: Università degli studi di Roma Foro Italico
name: Queen Mary University of London
name: Bios Prevention Srl
First posted: 2024-03-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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).
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: 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.

Primary outcomes:
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
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
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
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
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
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
Secondary outcomes:
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
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
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
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
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
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
Other outcomes:
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
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
Locations:
city: Tivoli
country: Italy
facility: Acque Albule, Terme di Roma
state: Rome
Study officials:
affiliation: La Sapienza, University of Rome
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
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