xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06018649</url>
    </required_header>
    <id_info>
      <org_study_id>BE-2-87</org_study_id>
      <nct_id>NCT06018649</nct_id>
    </id_info>
    <brief_title>The Effectiveness of Natural Resources for Reducing Stress</brief_title>
    <acronym>LUGISES</acronym>
    <official_title>The Effectiveness and Safety of Using Lithuania's Natural Resources to Improve Stress-related Mental and Physical Health</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Klaipėda University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Research Council of Lithuania</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Klaipėda University</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        High levels of stress cause serious health problems and reduce the quality of life. There is&#xD;
        a lack of research proving the use of natural resources for the treatment or prevention of&#xD;
        the stress and recovery from post Covid-19 condition. The goal of research: to assess the&#xD;
        impact of natural resources (geothermal/mineral water, mud, salt, climate) on reducing stress&#xD;
        and improving stress-related mental and physical health, as well as the safety of the&#xD;
        procedures. The study will be randomized, controlled, parallel group, single- blinded (to&#xD;
        researchers). The complex of procedures of water pool, mineral water bath, mud wrapping, salt&#xD;
        therapy, nature therapy procedure will be provided with the different duration and mode&#xD;
        (inpatient, outpatient). Primary outcomes- the effect on stress level; secondary outcomes:&#xD;
        the effects on stress-related mental and physical health, work and social adaptation,&#xD;
        tolerance and safety of balneotherapy procedures. The observation: before, after treatment,&#xD;
        after 3 and 6 month of follow-up will be reveled.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The burden of stress and the consequences of Covid-19 pandemia complicates the existing&#xD;
        capacities of the health care system and harms the efficiency and economy, therefore&#xD;
        effective strategies are needed to reduce the consequences by creating science-based&#xD;
        methodologies to strengthen and restore health in resorts, which would encourage wellness&#xD;
        services, using the unique natural resources available in Lithuanian resorts and resort&#xD;
        areas, development and would allow to compete with the most advanced European health and&#xD;
        rehabilitation centers.&#xD;
  &#xD;
        Objectives of biomedical research:&#xD;
  &#xD;
          1. To assess the effectiveness of Lithuania's unique natural resources in reducing stress&#xD;
             and improving stress-related mental and physical conditions.&#xD;
  &#xD;
          2. After identifying the group of those who have recovered from Covid-19, evaluate the&#xD;
             effectiveness of natural factors for improving this condition.&#xD;
  &#xD;
          3. To present methodological recommendations for the use of Lithuania's natural resources.&#xD;
  &#xD;
        Hypotheses of biomedical research:&#xD;
  &#xD;
          1. It is likely that a complex of procedures using natural resources will reduce stress,&#xD;
             anxiety, and depression.&#xD;
  &#xD;
          2. It is likely that procedures with nature factors improve work and social adaptation.&#xD;
  &#xD;
          3. The effect of natural resource therapy is effective regardless of the duration of&#xD;
             treatment and season.&#xD;
  &#xD;
        A multicenter, prospective, randomized controlled, single-blinded parallel group scientific&#xD;
        study will be made.&#xD;
  &#xD;
        Participants: 330 participants experiencing increased and poorly controlled stress or reduced&#xD;
        sense of well-being in Klaipėda and Druskininkai territories (6 groups of 55 people each).&#xD;
        Sampling is a probabilistic nest (cluster), in which each research participant's entry into&#xD;
        the sample is multi-stage, criterion-referenced. The sample size required for statistically&#xD;
        significant comparisons of the rehabilitation effect of the means of quantitative variables&#xD;
        before and after the procedures was calculated by the G*Power program.&#xD;
  &#xD;
          -  The subject will be randomly assigned to the respective group (I-VI) by a computer&#xD;
             program after the initial examination (T0) at the study centers. Grouping will be done&#xD;
             by a statistician.&#xD;
  &#xD;
          -  • coding/blinding (if applicable, a description is provided so that no one (subjects,&#xD;
             researchers, statisticians, etc.) will know which group the subject belongs to),&#xD;
  &#xD;
          -  After the initial screening, the completed questionnaires will be modally coded by a&#xD;
             statistician. The researchers conducting the clinical trial will not know which group&#xD;
             the subject belongs to.&#xD;
  &#xD;
        Group I will be given a complex of balneological procedures: swimming pool 20 min, 34-36°&#xD;
        mineral/geothermal water procedure 20 min, sapropel wrapping 20 min, salt therapy 25 min.&#xD;
        Duration of treatment - 6 days.&#xD;
  &#xD;
        Group II will be given a complex of balneological procedures as group I. Duration of&#xD;
        treatment - 11 days. Comparing the results of groups I and II will allow us to assess the&#xD;
        influence of treatment duration.&#xD;
  &#xD;
        Group III will be given a complex of balneological procedures like groups I and II and a&#xD;
        natural therapy procedure developed by the researchers: a 45-minute walk in nature (forest,&#xD;
        seaside), a complex of simple strength and breathing low-intensity exercises, sensory&#xD;
        impulses (landscape , forest smells - aromatherapy, natural sounds of nature, collecting&#xD;
        nature's goodies (berries, pine cones, leaves, etc.), awareness therapy,&#xD;
        heliotherapy.Duration - 11 days. Comparison of groups I and II will allow to evaluate the&#xD;
        influence of complex treatment, including nature therapy.&#xD;
  &#xD;
        Group IV will be accommodated in the research center and will receive balneological&#xD;
        treatments (as groups I and II). Duration of treatment 11 days. Comparison of the effect&#xD;
        between groups I, II, III and IV will allow to assess the impact of inpatient rehabilitation&#xD;
        treatment relatively.&#xD;
  &#xD;
        Group V will be given only the natural therapy procedure (as in group III). Duration 11 days&#xD;
        The results will make it possible to evaluate the benefits of the natural therapy procedure,&#xD;
        which can be applied by the person himself to improve or restore health. Comparison with the&#xD;
        results of group II will allow to evaluate the benefits of treatment with balneotherapy&#xD;
        procedures in the institution.&#xD;
  &#xD;
        Group VI - the control group, the participants of which will not be given any procedures.&#xD;
        Duration 11 days Comparison with groups II, IV, V will allow us to evaluate the differences&#xD;
        in the health effects of rehabilitation procedures and natural therapy compared to no&#xD;
        treatment.&#xD;
  &#xD;
        During the study, the sociodemographic, clinical, health, body condition and safety&#xD;
        assessment data of the study participants will be collected. Data will be collected based&#xD;
        only on the information provided by the participant and the results obtained during the&#xD;
        study. The screening questionnaire will ask for gender, age, marital status, education, place&#xD;
        of residence, nature of work, length of service and earnings, information on the occurrence&#xD;
        of Covid-19 and the incidence of chronic diseases, lifestyle habits, the level of stress&#xD;
        experienced and methods of management, the sense of well-being experienced and information ,&#xD;
        which is important when including in the study - the current exacerbation of a chronic&#xD;
        disease; morbidity from an oncological or infectious disease, severe form of cardiovascular,&#xD;
        nervous, mental, kidney disease or bleeding, recent surgery or major trauma, limitation of&#xD;
        movement function; possible pregnancy or breastfeeding; Intolerance of balneotherapy&#xD;
        treatment or thermal procedures applied during the 3-month period and plans to leave in the&#xD;
        next 6 months, which would not ensure your participation in the entire study period.&#xD;
  &#xD;
        During the study, objective measurements will be performed to determine the response of&#xD;
        various body systems: BP (blood pressure), HR (heart rate), SpO2 (pulsoxymetry), spirometry,&#xD;
        toe-to-floor distance, sit-to-reach test, dynamometry, body composition analysis, waist&#xD;
        circumference, salivary cortisol, cognitive test set (alertness, working memory, spatial&#xD;
        number search, logical reasoning). The results of the scales will be used to evaluate the&#xD;
        results of the study: for stress - the perceived stress scale (PSS) and the General Distress&#xD;
        Symptoms Scale (GSDS), for anxiety - the Anxiety and Restlessness Inventory (STAI), for&#xD;
        depression - the Center for Epidemiological Research Revised Depression Scale (CESD-R-20),&#xD;
        for fatigue - Multidimensional Fatigue Inventory (FAS), for sleep - one-point sleep quality&#xD;
        scale (SQS), for adaptation - Work and Social Adaptation Scale (WSAS), for well-being -&#xD;
        Arizona Integrative Outcomes Scale (AIOS), for general health and well-being - health&#xD;
        questionnaire, procedures security assessment questionnaire.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Active, not recruiting</overall_status>
    <start_date type="Actual">January 2, 2023</start_date>
    <completion_date type="Anticipated">March 1, 2024</completion_date>
    <primary_completion_date type="Anticipated">September 15, 2023</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>In a parallel study 6 groups of participants will receive different interventions modalities (duration, procedures complex, inpatient/outpatient, control). Participants will be assigned to one of the treatment arms at the beginning of the trial and continue in that arm throughout the length of the trial. Assignment to a group will be randomized. There will be possibility to compare few treatments modalities results.</intervention_model_description>
      <primary_purpose>Prevention</primary_purpose>
      <masking>Double (Investigator, Outcomes Assessor)</masking>
      <masking_description>The subject will be randomly assigned to the study group (I-VI) by a computer program after the initial examination (T0) at the study centers. Grouping will be done by a statistician. Coding/blinding will be done so that researchers, statisticians, etc. will not know which group the subject belongs to. After the initial screening, the completed questionnaires will be modally coded by a statistician. The researchers conducting the clinical trial will not know which group the subject belongs to.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>General Symptom Distress Scale (GSDS)</measure>
      <time_frame>6 month</time_frame>
      <description>The GSDS is a brief self-reported measure to assess intensity (0 (I don't have this symptom) - 10 scale (extremely bothersome) of specific symptoms relevant to stress. In the second section of the GSDS, participants are asked to provide a global rating of how distressing their symptoms are on a 10-point scale, with higher scores indicating more distress. In the third part, participants are asked to provide a global rating of how well they are able to manage their symptoms on a 10-point scale with higher scores indicating better ability to manage symptoms.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>PSS-10 (Perceived Stress Scale)</measure>
      <time_frame>6 month</time_frame>
      <description>It is a self-reported questionnaire to measure the degree to which situations in one's life. There are described 10 items which are appraised as stressful and participant should sign 1-4 points to each. Individual scores on the PSS can range from 0 to 40 with higher scores indicating higher perceived stress. ► Scores ranging from 0-13 would be considered low stress. ► Scores ranging from 14-26 would be considered moderate stress. ► Scores ranging from 27-40 would be considered high perceived stress.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Cortisol level in saliva</measure>
      <time_frame>Treatment (1- 2 weeks)</time_frame>
      <description>Specified amount of saliva is taken into dispenser and the amount of cortisol in it is tested in sertified laboratory (Germany). Higher cortisol numbers indicate higher stress levels.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Anxiety by STAI-5- Spielberger State-Trait Anxiety Inventory</measure>
      <time_frame>6 month</time_frame>
      <description>The five-item short forms of STAIS and STAIT are given. A number of statements which people have used to describe themselves are given for the signing answer which seems to describe respondent's present feelings best. For STAIS- HOW YOU FEEL RIGHT NOW, for STAIT- HOW YOU GENERALLY FEEL in 1-4 score, where 1 means Not at all, 4- Very much so. Cutoff scores for state STAIS (&gt;9.5) and trait STAIT(&gt;13.5) anxiety.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Work and social adjustment by WSAS (work and social adjustment scale)</measure>
      <time_frame>6 month</time_frame>
      <description>The effect will be measured by WSAS (work and social adjustment) scale</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The safety of balneotherapy</measure>
      <time_frame>After treatment (1-2 weeks)</time_frame>
      <description>A questionnaire with 24 symptoms (redness, itching, dryness, infection, peeling, rash, red eyes, dizziness, pain, depression, insomnia, fatigue, stress, terminal pain, nausea, loss of appetite, heart palpitations, increase in blood pressure, decrease , thirst, cough, shortness of breath, general deterioration of health, and others (for enquiry) will be given to to express undesirable effects during water, mud and salt procedures. The respondent in the table indicates 1- never, 2- rarely, 3- often, 4- always, 5- required treatment. At the end participant generally assess the safety of all balneotherapy procedures at 5-point Likert scale, where 1 is very safe, 5- unsafe.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effect on depression- CESD-R (Center for Epidemiological Studies Depression Scale )</measure>
      <time_frame>6 month</time_frame>
      <description>It is a 20-item measure of depressive symptoms. The list with 20 items identifies how respondent may be feeling or behaving recently. They need to check the boxes that apply how many times he have felt this way in the past week or longer. 1- Not suitable at all or Less than 1 day, 2- 1-2 days, 3- 3-4 days, 4- 5-7 days, 5- almost every day for two weeks. Bigger number means more severe depression.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effect on fatigue- FAS-10 (Fatigue scale)</measure>
      <time_frame>6 month</time_frame>
      <description>The scale has 10 items. Each FAS question is answered using a five-point Likert-type scale ranging from 1 (&quot;never&quot;) to 5 (&quot;always&quot;). Points 4 and 10 are evaluated in contrast. The total score can range from 10, indicating the lowest level of fatigue, to 50, indicating the highest.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>AIOS (Arizona Integrative Outcomes Scale)</measure>
      <time_frame>6 month</time_frame>
      <description>AIOS scale (Arizona Integrative Outcomes Scale is a single-item visual analog scale (AIOS) where the items self-rate the overall sense of spiritual, social, mental, emotional, and physical well-being over the past 24 hours or the past month. Respondent Mark the line below with an X at the point that summarizes your overall sense of well-being for the past 24 hours from Worst you have ever been to best you have ever been.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Sleep quality</measure>
      <time_frame>6 month</time_frame>
      <description>SQS (Single-Item Sleep Scale (Snyder E, 2018). This is a single-item sleep quality scale. The SQS is easily self-administered administered a questionnaire that uses a visual analog scale.The questionnaire instructions instruct the respondent to rate overall sleep quality over a 7-day period on a VAS from 0 to 10 based on the following five categories: 0 = terrible, 1-3 = poor, 4-6 = fair, 7- 9 = good and 10 = excellent When assessing sleep quality, respondents are asked to consider the following key components of sleep quality: how many hours they slept, how easily they fell asleep, how often they woke up during the night (except for going to the bathroom), how often they woke up earlier than they should, and how rested felt after sleep.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cognitive function</measure>
      <time_frame>6 month</time_frame>
      <description>Cognitive function will be measured using licenced RehaCom software screening tests (working memory, attention, working speed, attention span). Bigger positive results means better function, negative results- bad function.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Forced vital capacity</measure>
      <time_frame>6 month</time_frame>
      <description>FVC-Forced vital capacity- the total volume of air that can be exhaled during a maximal forced expiration effort measured in litres.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Forced expiratory volume</measure>
      <time_frame>6 month</time_frame>
      <description>The forced expiratory volume in 1 second (FEV1) is the volume of air (in liters) exhaled in the first second during forced exhalation after maximal inspiration.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Peak expiratory flow</measure>
      <time_frame>6 month</time_frame>
      <description>PEF is measured during routine spirometry. Peak expiratory flow (PEF) is given in litres of air breathed out per minute (l/min).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Blood pressure</measure>
      <time_frame>6 month</time_frame>
      <description>Measuring systolic and diastolic blood pressure (mmHg)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Heart rate</measure>
      <time_frame>6 month</time_frame>
      <description>Heart rate in times per minute</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Oxygen saturation</measure>
      <time_frame>6 month</time_frame>
      <description>Using a pulse oximeter we will measure oxygen saturation. It is a noninvasive device placed over a person's finger. It measures light wavelengths to determine the ratio of the current levels of oxygenated hemoglobin to deoxygenated hemoglobin.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Skin condition</measure>
      <time_frame>6 month</time_frame>
      <description>Skin condition will be measured: moisture, oiliness, elasticity (TMISHION Skin Tester, Model: M-6602). Portable Instrument Skin Oil Content Moisture Analyzer will measure skin moisture, oiliness, elasticity degree using bio-resistance technology which can accurately detect the health value of the skin, further understand the skin condition. The inductive probe can sense the skin condition, and can monitor the degree of whitening, moisture, oil content and skin elasticity. Higher degree indicate higher parameter measured.</description>
    </secondary_outcome>
    <number_of_arms>6</number_of_arms>
    <enrollment type="Actual">330</enrollment>
    <condition>Distress, Emotional</condition>
    <condition>COVID-19</condition>
    <arm_group>
      <arm_group_label>Short ambulatory balneotherapy (SAB)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Group I will be given a complex of balneological procedures: swimming pool 20 min, 34-36° mineral/geothermal water procedure 20 min, sapropel wrapping 20 min, salt therapy 25 min. Duration of treatment - 6 days, outpatient.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Long ambulatory balneotherapy (LAB)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Group II will be given a complex of balneological procedures as group I- swimming pool 20 min, 34-36° mineral/geothermal water procedure 20 min, sapropel wrapping 20 min, salt therapy 25 min.&#xD;
  Duration of treatment - 11 days, outpatient treatment.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Combined nature resources treatment (CNT)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Group III will be given a complex of balneological procedures like groups I and II plus natural therapy procedure developed by the researchers: a 45-minute walk in nature (forest, seaside), a complex of simple strength and breathing low-intensity exercises, sensory impulses (landscape , forest smells - aromatherapy, natural sounds of nature, collecting nature's goodies (berries, pine cones, leaves, etc.), awareness therapy, heliotherapy.&#xD;
  Duration - 11 days., outpatient treatment.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Long inpatient balneotherapy (LIB)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Group IV will be accommodated in the research/resort center and will receive balneological treatment (as groups I and II).&#xD;
  Duration of treatment 11 days, inpatient treatment.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Nature therapy (NT)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Group V will be given only the natural therapy procedure (as in group III). Duration 11 days, outpatient, self-managed according instructions and training provided.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>Group VI - the control group, the participants of which will not be given any procedures. Duration 11 days.</description>
    </arm_group>
    <intervention>
      <intervention_type>Combination Product</intervention_type>
      <intervention_name>Balneotherapy plus complex</intervention_name>
      <description>The three groups of study (SAB, LAB, LIB) will get same balneotherapy intervention with the difference in duration and mode (outpatient/inpatient). Balneotherapy plus complex procedures: swimming pool with light exercises- 20 min (29-31°C), rest 15 min, wrapping/bath with peloids (peat mud, sapropel)- 20 min (38-40°C), rest 20 min, mineral water bath- 20 min (36-38°C), salt therapy- 25 min (humidity 35%, temperature about 22°).</description>
      <arm_group_label>Long ambulatory balneotherapy (LAB)</arm_group_label>
      <arm_group_label>Long inpatient balneotherapy (LIB)</arm_group_label>
      <arm_group_label>Short ambulatory balneotherapy (SAB)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Combination Product</intervention_type>
      <intervention_name>Combined nature resources treatment</intervention_name>
      <description>The participants of CNT group will be given combined treatment: nature therapy procedure (45 min) and balneotherapy plus complex intervention procedures.&#xD;
  The nature therapy procedure was created by researchers by combining the principles of nature therapy, mindfulness, wild nature therapy, kinesiology selecting actions suitable for the season. A procedure instructions with specific steps will be prepared and given to the research participant. The procedure will be performed for the first time by a physiotherapist, the rest of the procedures are performed independently, following the detailed procedure with written instructions given to the participants. Each day participants will receive a message with a reminder to perform the natural therapy procedure. Duration of procedure- 45 min, outside (seaside, forest).</description>
      <arm_group_label>Combined nature resources treatment (CNT)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Nature therapy procedure</intervention_name>
      <description>The participants of NT group will be given nature therapy procedure (45 min) created by researchers by combining the principles of nature therapy, kinesiology, mindfulness, wild nature therapy, selecting actions suitable for the season. A procedure instruction with specific steps will be prepared and given to the research participant. The procedure will be performed for the first time by a physiotherapist, the rest of the procedures are performed independently, following the detailed procedure with written instructions given to the participants. Each day participants will receive a message with a reminder to perform the natural therapy procedure. Duration of procedure- 45 min, outside (seaside, forest).</description>
      <arm_group_label>Nature therapy (NT)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age 18- 65 years&#xD;
  &#xD;
            -  Strength of stress &gt;3 (0 no stress - 10 unbearable stress, VAS) AND/OR&#xD;
  &#xD;
            -  Stress control &lt;7 (0- I can't control - 10- I control perfectly, VAS)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Uncontrolled/decompensated systemic diseases (hematological, endocrine,&#xD;
               rheumatological, renal, cardiovascular, digestive, pulmonary),&#xD;
  &#xD;
            -  Active infection,&#xD;
  &#xD;
            -  Malignant tumors,&#xD;
  &#xD;
            -  Surgery or major trauma in the past year,&#xD;
  &#xD;
            -  Impaired ability to walk,&#xD;
  &#xD;
            -  Applied balneotherapy treatment during a 3-month period,&#xD;
  &#xD;
            -  Pregnancy/lactation,&#xD;
  &#xD;
            -  Bleeding,&#xD;
  &#xD;
            -  Severe mental disorder.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Lolita Rapoliene, ass.prof.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Klaipėda University</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Klaipėda university</name>
        <address>
          <city>Klaipėda</city>
          <zip>LT-92294</zip>
          <country>Lithuania</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Lithuania</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 19, 2023</study_first_submitted>
    <study_first_submitted_qc>August 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 30, 2023</study_first_posted>
    <last_update_submitted>August 25, 2023</last_update_submitted>
    <last_update_submitted_qc>August 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 30, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Klaipėda University</investigator_affiliation>
      <investigator_full_name>Lolita Rapoliene</investigator_full_name>
      <investigator_title>Associate professor dr.</investigator_title>
    </responsible_party>
    <keyword>stress</keyword>
    <keyword>balneotherapy</keyword>
    <keyword>mineral water</keyword>
    <keyword>peloids</keyword>
    <keyword>mental state</keyword>
    <keyword>cortisol</keyword>
    <keyword>rehabilitation</keyword>
    <keyword>spa therapy</keyword>
    <keyword>hydrotherapy</keyword>
    <keyword>nature therapy</keyword>
    <keyword>resort medicine</keyword>
    <keyword>health</keyword>
    <keyword>natural resources</keyword>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
      <ipd_description>Sharing of participant data is possible by separate agreement, only for scientific purposes in the relevant field.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06018649
  org study id: BE-2-87
  nct id: NCT06018649
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  High levels of stress cause serious health problems and reduce the quality of life. There is
        a lack of research proving the use of natural resources for the treatment or prevention of
        the stress and recovery from post Covid-19 condition. The goal of research: to assess the
        impact of natural resources (geothermal/mineral water, mud, salt, climate) on reducing stress
        and improving stress-related mental and physical health, as well as the safety of the
        procedures. The study will be randomized, controlled, parallel group, single- blinded (to
        researchers). The complex of procedures of water pool, mineral water bath, mud wrapping, salt
        therapy, nature therapy procedure will be provided with the different duration and mode
        (inpatient, outpatient). Primary outcomes- the effect on stress level; secondary outcomes:
        the effects on stress-related mental and physical health, work and social adaptation,
        tolerance and safety of balneotherapy procedures. The observation: before, after treatment,
        after 3 and 6 month of follow-up will be reveled.
  The burden of stress and the consequences of Covid-19 pandemia complicates the existing
        capacities of the health care system and harms the efficiency and economy, therefore
        effective strategies are needed to reduce the consequences by creating science-based
        methodologies to strengthen and restore health in resorts, which would encourage wellness
        services, using the unique natural resources available in Lithuanian resorts and resort
        areas, development and would allow to compete with the most advanced European health and
        rehabilitation centers.
  
        Objectives of biomedical research:
  
          1. To assess the effectiveness of Lithuania's unique natural resources in reducing stress
             and improving stress-related mental and physical conditions.
  
          2. After identifying the group of those who have recovered from Covid-19, evaluate the
             effectiveness of natural factors for improving this condition.
  
          3. To present methodological recommendations for the use of Lithuania's natural resources.
  
        Hypotheses of biomedical research:
  
          1. It is likely that a complex of procedures using natural resources will reduce stress,
             anxiety, and depression.
  
          2. It is likely that procedures with nature factors improve work and social adaptation.
  
          3. The effect of natural resource therapy is effective regardless of the duration of
             treatment and season.
  
        A multicenter, prospective, randomized controlled, single-blinded parallel group scientific
        study will be made.
  
        Participants: 330 participants experiencing increased and poorly controlled stress or reduced
        sense of well-being in Klaipėda and Druskininkai territories (6 groups of 55 people each).
        Sampling is a probabilistic nest (cluster), in which each research participant's entry into
        the sample is multi-stage, criterion-referenced. The sample size required for statistically
        significant comparisons of the rehabilitation effect of the means of quantitative variables
        before and after the procedures was calculated by the G*Power program.
  
          -  The subject will be randomly assigned to the respective group (I-VI) by a computer
             program after the initial examination (T0) at the study centers. Grouping will be done
             by a statistician.
  
          -  • coding/blinding (if applicable, a description is provided so that no one (subjects,
             researchers, statisticians, etc.) will know which group the subject belongs to),
  
          -  After the initial screening, the completed questionnaires will be modally coded by a
             statistician. The researchers conducting the clinical trial will not know which group
             the subject belongs to.
  
        Group I will be given a complex of balneological procedures: swimming pool 20 min, 34-36°
        mineral/geothermal water procedure 20 min, sapropel wrapping 20 min, salt therapy 25 min.
        Duration of treatment - 6 days.
  
        Group II will be given a complex of balneological procedures as group I. Duration of
        treatment - 11 days. Comparing the results of groups I and II will allow us to assess the
        influence of treatment duration.
  
        Group III will be given a complex of balneological procedures like groups I and II and a
        natural therapy procedure developed by the researchers: a 45-minute walk in nature (forest,
        seaside), a complex of simple strength and breathing low-intensity exercises, sensory
        impulses (landscape , forest smells - aromatherapy, natural sounds of nature, collecting
        nature's goodies (berries, pine cones, leaves, etc.), awareness therapy,
        heliotherapy.Duration - 11 days. Comparison of groups I and II will allow to evaluate the
        influence of complex treatment, including nature therapy.
  
        Group IV will be accommodated in the research center and will receive balneological
        treatments (as groups I and II). Duration of treatment 11 days. Comparison of the effect
        between groups I, II, III and IV will allow to assess the impact of inpatient rehabilitation
        treatment relatively.
  
        Group V will be given only the natural therapy procedure (as in group III). Duration 11 days
        The results will make it possible to evaluate the benefits of the natural therapy procedure,
        which can be applied by the person himself to improve or restore health. Comparison with the
        results of group II will allow to evaluate the benefits of treatment with balneotherapy
        procedures in the institution.
  
        Group VI - the control group, the participants of which will not be given any procedures.
        Duration 11 days Comparison with groups II, IV, V will allow us to evaluate the differences
        in the health effects of rehabilitation procedures and natural therapy compared to no
        treatment.
  
        During the study, the sociodemographic, clinical, health, body condition and safety
        assessment data of the study participants will be collected. Data will be collected based
        only on the information provided by the participant and the results obtained during the
        study. The screening questionnaire will ask for gender, age, marital status, education, place
        of residence, nature of work, length of service and earnings, information on the occurrence
        of Covid-19 and the incidence of chronic diseases, lifestyle habits, the level of stress
        experienced and methods of management, the sense of well-being experienced and information ,
        which is important when including in the study - the current exacerbation of a chronic
        disease; morbidity from an oncological or infectious disease, severe form of cardiovascular,
        nervous, mental, kidney disease or bleeding, recent surgery or major trauma, limitation of
        movement function; possible pregnancy or breastfeeding; Intolerance of balneotherapy
        treatment or thermal procedures applied during the 3-month period and plans to leave in the
        next 6 months, which would not ensure your participation in the entire study period.
  
        During the study, objective measurements will be performed to determine the response of
        various body systems: BP (blood pressure), HR (heart rate), SpO2 (pulsoxymetry), spirometry,
        toe-to-floor distance, sit-to-reach test, dynamometry, body composition analysis, waist
        circumference, salivary cortisol, cognitive test set (alertness, working memory, spatial
        number search, logical reasoning). The results of the scales will be used to evaluate the
        results of the study: for stress - the perceived stress scale (PSS) and the General Distress
        Symptoms Scale (GSDS), for anxiety - the Anxiety and Restlessness Inventory (STAI), for
        depression - the Center for Epidemiological Research Revised Depression Scale (CESD-R-20),
        for fatigue - Multidimensional Fatigue Inventory (FAS), for sleep - one-point sleep quality
        scale (SQS), for adaptation - Work and Social Adaptation Scale (WSAS), for well-being -
        Arizona Integrative Outcomes Scale (AIOS), for general health and well-being - health
        questionnaire, procedures security assessment questionnaire.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: In a parallel study 6 groups of participants will receive different interventions modalities (duration, procedures complex, inpatient/outpatient, control). Participants will be assigned to one of the treatment arms at the beginning of the trial and continue in that arm throughout the length of the trial. Assignment to a group will be randomized. There will be possibility to compare few treatments modalities results.
  primary purpose: Prevention
  masking: Double (Investigator, Outcomes Assessor)
  masking description: The subject will be randomly assigned to the study group (I-VI) by a computer program after the initial examination (T0) at the study centers. Grouping will be done by a statistician. Coding/blinding will be done so that researchers, statisticians, etc. will not know which group the subject belongs to. After the initial screening, the completed questionnaires will be modally coded by a statistician. The researchers conducting the clinical trial will not know which group the subject belongs to.
  measure: General Symptom Distress Scale (GSDS)
  time frame: 6 month
  description: The GSDS is a brief self-reported measure to assess intensity (0 (I don't have this symptom) - 10 scale (extremely bothersome) of specific symptoms relevant to stress. In the second section of the GSDS, participants are asked to provide a global rating of how distressing their symptoms are on a 10-point scale, with higher scores indicating more distress. In the third part, participants are asked to provide a global rating of how well they are able to manage their symptoms on a 10-point scale with higher scores indicating better ability to manage symptoms.
  measure: PSS-10 (Perceived Stress Scale)
  time frame: 6 month
  description: It is a self-reported questionnaire to measure the degree to which situations in one's life. There are described 10 items which are appraised as stressful and participant should sign 1-4 points to each. Individual scores on the PSS can range from 0 to 40 with higher scores indicating higher perceived stress. ► Scores ranging from 0-13 would be considered low stress. ► Scores ranging from 14-26 would be considered moderate stress. ► Scores ranging from 27-40 would be considered high perceived stress.
  measure: Cortisol level in saliva
  time frame: Treatment (1- 2 weeks)
  description: Specified amount of saliva is taken into dispenser and the amount of cortisol in it is tested in sertified laboratory (Germany). Higher cortisol numbers indicate higher stress levels.
  measure: Anxiety by STAI-5- Spielberger State-Trait Anxiety Inventory
  time frame: 6 month
  description: The five-item short forms of STAIS and STAIT are given. A number of statements which people have used to describe themselves are given for the signing answer which seems to describe respondent's present feelings best. For STAIS- HOW YOU FEEL RIGHT NOW, for STAIT- HOW YOU GENERALLY FEEL in 1-4 score, where 1 means Not at all, 4- Very much so. Cutoff scores for state STAIS (>9.5) and trait STAIT(>13.5) anxiety.
  measure: Work and social adjustment by WSAS (work and social adjustment scale)
  time frame: 6 month
  description: The effect will be measured by WSAS (work and social adjustment) scale
  measure: The safety of balneotherapy
  time frame: After treatment (1-2 weeks)
  description: A questionnaire with 24 symptoms (redness, itching, dryness, infection, peeling, rash, red eyes, dizziness, pain, depression, insomnia, fatigue, stress, terminal pain, nausea, loss of appetite, heart palpitations, increase in blood pressure, decrease , thirst, cough, shortness of breath, general deterioration of health, and others (for enquiry) will be given to to express undesirable effects during water, mud and salt procedures. The respondent in the table indicates 1- never, 2- rarely, 3- often, 4- always, 5- required treatment. At the end participant generally assess the safety of all balneotherapy procedures at 5-point Likert scale, where 1 is very safe, 5- unsafe.
  measure: Effect on depression- CESD-R (Center for Epidemiological Studies Depression Scale )
  time frame: 6 month
  description: It is a 20-item measure of depressive symptoms. The list with 20 items identifies how respondent may be feeling or behaving recently. They need to check the boxes that apply how many times he have felt this way in the past week or longer. 1- Not suitable at all or Less than 1 day, 2- 1-2 days, 3- 3-4 days, 4- 5-7 days, 5- almost every day for two weeks. Bigger number means more severe depression.
  measure: Effect on fatigue- FAS-10 (Fatigue scale)
  time frame: 6 month
  description: The scale has 10 items. Each FAS question is answered using a five-point Likert-type scale ranging from 1 ("never") to 5 ("always"). Points 4 and 10 are evaluated in contrast. The total score can range from 10, indicating the lowest level of fatigue, to 50, indicating the highest.
  measure: AIOS (Arizona Integrative Outcomes Scale)
  time frame: 6 month
  description: AIOS scale (Arizona Integrative Outcomes Scale is a single-item visual analog scale (AIOS) where the items self-rate the overall sense of spiritual, social, mental, emotional, and physical well-being over the past 24 hours or the past month. Respondent Mark the line below with an X at the point that summarizes your overall sense of well-being for the past 24 hours from Worst you have ever been to best you have ever been.
  measure: Sleep quality
  time frame: 6 month
  description: SQS (Single-Item Sleep Scale (Snyder E, 2018). This is a single-item sleep quality scale. The SQS is easily self-administered administered a questionnaire that uses a visual analog scale.The questionnaire instructions instruct the respondent to rate overall sleep quality over a 7-day period on a VAS from 0 to 10 based on the following five categories: 0 = terrible, 1-3 = poor, 4-6 = fair, 7- 9 = good and 10 = excellent When assessing sleep quality, respondents are asked to consider the following key components of sleep quality: how many hours they slept, how easily they fell asleep, how often they woke up during the night (except for going to the bathroom), how often they woke up earlier than they should, and how rested felt after sleep.
  measure: Cognitive function
  time frame: 6 month
  description: Cognitive function will be measured using licenced RehaCom software screening tests (working memory, attention, working speed, attention span). Bigger positive results means better function, negative results- bad function.
  measure: Forced vital capacity
  time frame: 6 month
  description: FVC-Forced vital capacity- the total volume of air that can be exhaled during a maximal forced expiration effort measured in litres.
  measure: Forced expiratory volume
  time frame: 6 month
  description: The forced expiratory volume in 1 second (FEV1) is the volume of air (in liters) exhaled in the first second during forced exhalation after maximal inspiration.
  measure: Peak expiratory flow
  time frame: 6 month
  description: PEF is measured during routine spirometry. Peak expiratory flow (PEF) is given in litres of air breathed out per minute (l/min).
  measure: Blood pressure
  time frame: 6 month
  description: Measuring systolic and diastolic blood pressure (mmHg)
  measure: Heart rate
  time frame: 6 month
  description: Heart rate in times per minute
  measure: Oxygen saturation
  time frame: 6 month
  description: Using a pulse oximeter we will measure oxygen saturation. It is a noninvasive device placed over a person's finger. It measures light wavelengths to determine the ratio of the current levels of oxygenated hemoglobin to deoxygenated hemoglobin.
  measure: Skin condition
  time frame: 6 month
  description: Skin condition will be measured: moisture, oiliness, elasticity (TMISHION Skin Tester, Model: M-6602). Portable Instrument Skin Oil Content Moisture Analyzer will measure skin moisture, oiliness, elasticity degree using bio-resistance technology which can accurately detect the health value of the skin, further understand the skin condition. The inductive probe can sense the skin condition, and can monitor the degree of whitening, moisture, oil content and skin elasticity. Higher degree indicate higher parameter measured.
  arm group label: Short ambulatory balneotherapy (SAB)
  arm group type: Experimental
  description: Group I will be given a complex of balneological procedures: swimming pool 20 min, 34-36° mineral/geothermal water procedure 20 min, sapropel wrapping 20 min, salt therapy 25 min. Duration of treatment - 6 days, outpatient.
  arm group label: Long ambulatory balneotherapy (LAB)
  arm group type: Experimental
  description: Group II will be given a complex of balneological procedures as group I- swimming pool 20 min, 34-36° mineral/geothermal water procedure 20 min, sapropel wrapping 20 min, salt therapy 25 min.
  Duration of treatment - 11 days, outpatient treatment.
  arm group label: Combined nature resources treatment (CNT)
  arm group type: Experimental
  description: Group III will be given a complex of balneological procedures like groups I and II plus natural therapy procedure developed by the researchers: a 45-minute walk in nature (forest, seaside), a complex of simple strength and breathing low-intensity exercises, sensory impulses (landscape , forest smells - aromatherapy, natural sounds of nature, collecting nature's goodies (berries, pine cones, leaves, etc.), awareness therapy, heliotherapy.
  Duration - 11 days., outpatient treatment.
  arm group label: Long inpatient balneotherapy (LIB)
  arm group type: Experimental
  description: Group IV will be accommodated in the research/resort center and will receive balneological treatment (as groups I and II).
  Duration of treatment 11 days, inpatient treatment.
  arm group label: Nature therapy (NT)
  arm group type: Active Comparator
  description: Group V will be given only the natural therapy procedure (as in group III). Duration 11 days, outpatient, self-managed according instructions and training provided.
  arm group label: Control
  arm group type: No Intervention
  description: Group VI - the control group, the participants of which will not be given any procedures. Duration 11 days.
  intervention type: Combination Product
  intervention name: Balneotherapy plus complex
  description: The three groups of study (SAB, LAB, LIB) will get same balneotherapy intervention with the difference in duration and mode (outpatient/inpatient). Balneotherapy plus complex procedures: swimming pool with light exercises- 20 min (29-31°C), rest 15 min, wrapping/bath with peloids (peat mud, sapropel)- 20 min (38-40°C), rest 20 min, mineral water bath- 20 min (36-38°C), salt therapy- 25 min (humidity 35%, temperature about 22°).
  arm group label: Long ambulatory balneotherapy (LAB)
  arm group label: Long inpatient balneotherapy (LIB)
  arm group label: Short ambulatory balneotherapy (SAB)
  intervention type: Combination Product
  intervention name: Combined nature resources treatment
  description: The participants of CNT group will be given combined treatment: nature therapy procedure (45 min) and balneotherapy plus complex intervention procedures.
  The nature therapy procedure was created by researchers by combining the principles of nature therapy, mindfulness, wild nature therapy, kinesiology selecting actions suitable for the season. A procedure instructions with specific steps will be prepared and given to the research participant. The procedure will be performed for the first time by a physiotherapist, the rest of the procedures are performed independently, following the detailed procedure with written instructions given to the participants. Each day participants will receive a message with a reminder to perform the natural therapy procedure. Duration of procedure- 45 min, outside (seaside, forest).
  arm group label: Combined nature resources treatment (CNT)
  intervention type: Other
  intervention name: Nature therapy procedure
  description: The participants of NT group will be given nature therapy procedure (45 min) created by researchers by combining the principles of nature therapy, kinesiology, mindfulness, wild nature therapy, selecting actions suitable for the season. A procedure instruction with specific steps will be prepared and given to the research participant. The procedure will be performed for the first time by a physiotherapist, the rest of the procedures are performed independently, following the detailed procedure with written instructions given to the participants. Each day participants will receive a message with a reminder to perform the natural therapy procedure. Duration of procedure- 45 min, outside (seaside, forest).
  arm group label: Nature therapy (NT)
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Lolita Rapoliene, ass.prof.
  role: Principal Investigator
  affiliation: Klaipėda University
  facility: 
  country: Lithuania
  responsible party type: Principal Investigator
  investigator affiliation: Klaipėda University
  investigator full name: Lolita Rapoliene
  investigator title: Associate professor dr.
  sharing ipd: Undecided
  ipd description: Sharing of participant data is possible by separate agreement, only for scientific purposes in the relevant field.