The Anti-inflammatory Effects of Harkány Medicinal Water

Study Overview
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Brief Summary
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The study aims to provide evidence on the effectiveness of Harkány medicinal water in psoriatic and rheumatoid arthritis patients using subjective and objective methods. It is a cross-over study, so first half of patients will receive medicinal water, the other half will receive tap water treatment, and after 6 months treatments will be repeated, but patients will receive the other type of water.

Detailed Description
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Several studies have shown that medicinal waters are highly effective in the treatment of many diseases. Existing clinical trials were unable to provide scientific evidence by using the highest international standards to justify the efficiency of thermal waters. Harkány medicinal water has been used for rheumatic, skin and locomotor diseases for more than 100 years. Its beneficial effects are indisputable. However, to introduce these effects, internationally high-level scientific methods and investigations are needed. Psoriasis is among the most common dermatological diseases worldwide. Its significance is emphasized by adverse effects on quality of life, caused by chronic pain, physical and psychical disability due to psoriatic plaques. Former studies revealed an increased risk of inflammatory bowel disease, cardiovascular disease and certain types of cancer. Moreover, excessive oxidative stress can be responsible for the onset of psoriasis complications. Rheumatoid arthritis (RA) is an autoimmune disease responsible for significant morbidity, characterized by articular inflammation. Oxidative stress is a key marker for determining pathophysiology of patients with RA. The pathophysiological link between these conditions is the presence of excessive oxidative stress. Subjective methods will include questionnaires, objective markers of disease severity will include the measurement of biomarkers from blood samples.

Official Title
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The Anti-inflammatory Effects of Harkány Medicinal Water

Conditions
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Rheumatoid Arthritis, Psoriasis

Intervention / Treatment
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* Other: Harkány medicinal water
* Other: Tap water (placebo control)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: signed consent statement over 18 years of age lack of underlying renal disease (GFR >60 mL/min/1.73m2) lack of severe inflammation (WBC <20.000 G/l; CRP <50 mg/l; WE <40 mm/h) psoriasis vulgaris with skin lesions mild and inactive RA Exclusion Criteria: having received any kind of balneotherapy within 1 year before admission discontinuance of rehabilitation withdrawal of consent clinically significant difference in severity of the patient's condition on 1st or 2nd admission severe RA patients suffering from cancer patients suffering from inflammatory bowel disease patients underwent stroke within 1 year severe hypercholesterolemia severe diabetes patients with renal insufficiency patients receiving any kind biological therapy patients whose medication has changed during the study period or one month prior to the second treatment session

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Psoriasis / RA (t=0) Control (t=1) ---> (t=3) Medicinal water (t=4) (t=0) Medicinal water (t=1) ---> (t=3) Control (t=4) After 6 months, treatments will be repeated, but transposed, the previously control patients will receive medicinal water treatment, and tap water treatment will be performed on the previously treated group.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Medicinal water treated group<br>3-week-long inward rehabilitation, in a bath tab, for 30 min, 5 days a week. (After 6 months treatments will be repeated in tap water.) | Other: Harkány medicinal water<br>* The aim is to prove the effectiveness of Harkány medicinal water on patients suffering from psoriasis and rheumatoid arthritis. The control group is treated with tap water.<br>|
| Placebo Comparator: Tap water treated group<br>3-week-long inward rehabilitation, in a bath tab, for 30 min, 5 days a week. (After 6 months treatments will be repeated in medicinal water.) | Other: Tap water (placebo control)<br>* The control group is treated with tap water.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dermatology Life Quality Index (DLQI) | Self reported questionnaire is to measure how much the skin problem has affected the patient's life over the last week. The scoring of each question is as follows: Very much - scored 3; A lot - scored 2; A little - scored 1; Not at all - scored 0; Not relevant - scored 0; Question 7, 'prevented work or studying' - scored 3. The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. | baseline (on admission) | 
| Functional Independence Measure (FIM) | It is an 18-item measurement tool that explores an individual's physical, psychological and social function. The tool is used to assess a patient's level of disability as well as change in patient status in response to rehabilitation or medical intervention. Each item is scored 1-7. No Helper: 7. Complete Independence (Timely, Safety); 6. Modified Independence (Device) Helper - Modified Dependence: 5. Supervision (Subject = 100%); 4. Minimal Assistance (Subject = 75% or more); 3. Moderate Assistance (Subject = 50% or more) Helper - Complete Dependence: 2. Maximal Assistance (Subject = 25% or more); 1. Total Assistance or not Testable (Subject less than 25%) | baseline (on admission) | 
| SF-36 | This questionnaire contains 36 items that assess patients' health status and its impact on their lives. SF-36 is a structured, self-report questionnaire that a patient can complete with little or no counseling from an interviewer. Answers to the questions yield eight domains [scored from 0 (low) to 100 (high)] and two summary physical and mental component scores (PCS and MCS). | baseline (on admission) | 
| Patient Uncertainty Questionnaire-Rheumatology (PUQ-R) | Questions about issues related to arthritis. Each item is scored 1-4 (1 = very uncertain, 4 = very certain). Patients answer each question according to how certain or uncertain they are about each issues. | baseline (on admission) | 
| Psoriasis Area Severity Index (PASI) | It is used to express the severity of psoriasis. It combines the severity (erythema, induration and desquamation) and percentage of affected area. For each body section (head, arms, trunk and legs) the percent of area of skin involved and the severity of three clinical signs (erythema, induration and desquamation) on a scale from 0 to 4 (from none to maximum) are to be specified. | baseline (on admission) | 
| Disease Activity Score Calculator for Rheumatoid Arthritis (DAS 28) | It makes an objective, reproducible and comparable assessment of the rheumatoid arthritis activity. It takes into account the following items: TJC28: The number of tender joints (0-28). SJC28: The number of swollen joints (0-28). ESR: The Erythrocyte Sedimentation Rate (in mm/h). GH: The patient global health assessment (from 0=best to 100=worst). The 28 tender or swollen joint scores target the same joints (shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints and the knees). | baseline (on admission) | 
| White blood cell count (Routine laboratory parameter) | Aspecific test for monitoring inflammation. | baseline (on admission) | 
| Haemoglobin (Routine laboratory parameter) | Part of general laboratory test. | baseline (on admission) | 
| Haematocrit (Routine laboratory parameter) | Part of general laboratory test. | baseline (on admission) | 
| WE (Routine laboratory parameter) | Aspecific test for monitoring inflammation. | baseline (on admission) | 
| Creatinine /eGFR/ (Routine laboratory parameter) | General kidney function. | baseline (on admission) | 
| Uric acid (Routine laboratory parameter) | Aspecific marker of antioxidant system. | baseline (on admission) | 
| High sensitivity C-reactive protein (hs-CRP) | hs-CRP is an aspecific inflammatory parameter, involved in most risk evaluation systems and generally used in clinical practice. | baseline (on admission) | 
| Asymmetric dimethylarginine (ADMA) | ADMA is considered as a marker and mediator of oxidative stress and an indicator of vascular well-being. | baseline (on admission) | 
| Total antioxidant capacity (TAC) | TAC is an easily feasible, widely used method, indirect marker of oxidative stress. | baseline (on admission) | 
| Malondialdehyde (MDA) | MDA is a well-known biomarker of oxidative stress. It is also a sensitive marker of inflammation in patients with RA. | baseline (on admission) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dermatology Life Quality Index (DLQI) | Self reported questionnaire is to measure how much the skin problem has affected the patient's life over the last week. The scoring of each question is as follows: Very much - scored 3; A lot - scored 2; A little - scored 1; Not at all - scored 0; Not relevant - scored 0; Question 7, 'prevented work or studying' - scored 3. The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. | 3 weeks (before discharge) | 
| Functional Independence Measure (FIM) | It is an 18-item measurement tool that explores an individual's physical, psychological and social function. The tool is used to assess a patient's level of disability as well as change in patient status in response to rehabilitation or medical intervention. Each item is scored 1-7. No Helper: 7. Complete Independence (Timely, Safety); 6. Modified Independence (Device) Helper - Modified Dependence: 5. Supervision (Subject = 100%); 4. Minimal Assistance (Subject = 75% or more); 3. Moderate Assistance (Subject = 50% or more) Helper - Complete Dependence: 2. Maximal Assistance (Subject = 25% or more); 1. Total Assistance or not Testable (Subject less than 25%) | 3 weeks (before discharge) | 
| SF-36 | This questionnaire contains 36 items that assess patients' health status and its impact on their lives. SF-36 is a structured, self-report questionnaire that a patient can complete with little or no counseling from an interviewer. Answers to the questions yield eight domains [scored from 0 (low) to 100 (high)] and two summary physical and mental component scores (PCS and MCS). | 3 weeks (before discharge) | 
| Patient Uncertainty Questionnaire-Rheumatology (PUQ-R) | Questions about issues related to arthritis. Each item is scored 1-4 (1 = very uncertain, 4 = very certain). Patients answer each question according to how certain or uncertain they are about each issues. | 3 weeks (before discharge) | 
| Psoriasis Area Severity Index (PASI) | It is used to express the severity of psoriasis. It combines the severity (erythema, induration and desquamation) and percentage of affected area. For each body section (head, arms, trunk and legs) the percent of area of skin involved and the severity of three clinical signs (erythema, induration and desquamation) on a scale from 0 to 4 (from none to maximum) are to be specified. | 3 weeks (before discharge) | 
| Disease Activity Score Calculator for Rheumatoid Arthritis (DAS 28) | It makes an objective, reproducible and comparable assessment of the rheumatoid arthritis activity. It takes into account the following items: TJC28: The number of tender joints (0-28). SJC28: The number of swollen joints (0-28). ESR: The Erythrocyte Sedimentation Rate (in mm/h). GH: The patient global health assessment (from 0=best to 100=worst). The 28 tender or swollen joint scores target the same joints (shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints and the knees). | 3 weeks (before discharge) | 
| White blood cell count (Routine laboratory parameter) | Aspecific test for monitoring inflammation. | 3 weeks (before discharge) | 
| WE (Routine laboratory parameter) | Aspecific test for monitoring inflammation. | 3 weeks (before discharge) | 
| Creatinine /eGFR/ (Routine laboratory parameter) | General kidney function. | 3 weeks (before discharge) | 
| Uric acid (Routine laboratory parameter) | Aspecific marker of antioxidant system. | 3 weeks (before discharge) | 
| High sensitivity C-reactive protein (hs-CRP) | hs-CRP is an aspecific inflammatory parameter, involved in most risk evaluation systems and generally used in clinical practice. | 3 weeks (before discharge) | 
| Asymmetric dimethylarginine (ADMA) | ADMA is considered as a marker and mediator of oxidative stress and an indicator of vascular well-being. | 3 weeks (before discharge) | 
| Total antioxidant capacity (TAC) | TAC is an easily feasible, widely used method, indirect marker of oxidative stress. | 3 weeks (before discharge) | 
| Malondialdehyde (MDA) | MDA is a well-known biomarker of oxidative stress. It is also a sensitive marker of inflammation in patients with RA. | 3 weeks (before discharge) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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medicinal water,inflammation,biomarker,inflammatory disease