The Anti-inflammatory Effects of Harkány Medicinal Water

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.

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis; Psoriasis
• Intervention / Treatment: Other: Harkány medicinal water; Other: Tap water (placebo control)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 350
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Katalin Dr Szendi, MD, PhD; Phone Number: +3672536396; Email: szkata82@yahoo.co.uk
• Study Contact Backup: Name: Balázs Dr Németh, MD, PhD; Phone Number: +3672536037; Email: nem_bal2@hotmail.com

Study Locations

• Hungary
  • Baranya
    • Pécs, Baranya, Hungary, 7624
      • Recruiting
      • Katalin Dr Szendi
      • Contact: Katalin Dr Szendi, MD, PhD; Phone Number: +3672536396; Email: szkata82@yahoo.co.uk
      • Contact: Balázs Dr Németh, MD, PhD; Phone Number: +3672536037; Email: nem_bal2@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Medicinal water treated group; 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; 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.
Placebo Comparator: Tap water treated group; 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); The control group is treated with tap water.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University of Pecs
• Collaborators: National Research, Development and Innovation Office, Hungary; Harkány Spa Hospital, Hungary

Publications and helpful links

General Publications

• Szendi K, Gerencsér G, Murányi E, Varga Cs. Mutagenic activity of peloids in the Salmonella Ames test. Applied Clay Science 55: 70-74, 2012.
• Gerencsér G, Murányi E, Szendi K, Varga Cs. Ecotoxicological studies on Hungarian peloids (medicinal muds). Applied Clay Science 50(1): 47-50, 2010.
• Varga C, Laszlo M, Gerencser G, Gyongyi Z, Szendi K. Natural UV-protective organic matter in thermal water. J Photochem Photobiol B. 2015 Mar;144:8-10. doi: 10.1016/j.jphotobiol.2015.01.007. Epub 2015 Jan 22.
• Gerencser G, Szendi K, Berenyi K, Varga C. Can the use of medical muds cause genotoxicity in eukaryotic cells? A trial using comet assay. Environ Geochem Health. 2015 Feb;37(1):63-70. doi: 10.1007/s10653-014-9630-7. Epub 2014 Jul 26.
• Peter I, Jagicza A, Ajtay Z, Boncz I, Kiss I, Szendi K, Kustan P, Nemeth B. Balneotherapy in Psoriasis Rehabilitation. In Vivo. 2017 Nov-Dec;31(6):1163-1168. doi: 10.21873/invivo.11184.
• Szendi K, Gyöngyi Z, Kontár Zs, Gerencsér G, Berényi K, Hanzel A, Fekete J, Kovács A, Varga Cs. Mutagenicity and Phthalate Level of Bottled Water Under Different Storage Conditions. Exposure and Health 10(1): 51-60, 2018.
• Hanzel A, Horvat K, Molics B, Berenyi K, Nemeth B, Szendi K, Varga C. Clinical improvement of patients with osteoarthritis using thermal mineral water at Szigetvar Spa-results of a randomised double-blind controlled study. Int J Biometeorol. 2018 Feb;62(2):253-259. doi: 10.1007/s00484-017-1446-6. Epub 2017 Sep 27.
• Hanzel A, Berenyi K, Horvath K, Szendi K, Nemeth B, Varga C. Evidence for the therapeutic effect of the organic content in Szigetvar thermal water on osteoarthritis: a double-blind, randomized, controlled clinical trial. Int J Biometeorol. 2019 Apr;63(4):449-458. doi: 10.1007/s00484-019-01676-3. Epub 2019 Feb 7.
• Nemeth B, Ajtay Z, Hejjel L, Ferenci T, Abram Z, Muranyi E, Kiss I. The issue of plasma asymmetric dimethylarginine reference range - A systematic review and meta-analysis. PLoS One. 2017 May 11;12(5):e0177493. doi: 10.1371/journal.pone.0177493. eCollection 2017.
• Nemeth B, Kustan P, Nemeth A, Lenkey Z, Cziraki A, Kiss I, Sulyok E, Ajtay Z. [Asymmetric dimethylarginine: predictor of cardiovascular diseases?]. Orv Hetil. 2016 Mar 27;157(13):483-7. doi: 10.1556/650.2016.30396. Hungarian.
• Peter I, Jagicza A, Ajtay Z, Kiss I, Nemeth B. [Psoriasis and oxidative stress]. Orv Hetil. 2016 Nov;157(45):1781-1785. doi: 10.1556/650.2016.30589. Hungarian.
• Kalavacherla US, Ishaq M, Rao UR, Sachindranath A, Hepsiba T. Malondialdehyde as a sensitive marker of inflammation in patients with rheumatoid arthritis. J Assoc Physicians India. 1994 Oct;42(10):775-6.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2020
• Primary Completion (Anticipated): November 30, 2020
• Study Completion (Anticipated): November 30, 2023

Study Registration Dates

• First Submitted: February 14, 2020
• First Submitted That Met QC Criteria: February 14, 2020
• First Posted (Actual): February 19, 2020

Study Record Updates

• Last Update Posted (Actual): June 9, 2020
• Last Update Submitted That Met QC Criteria: June 6, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: medicinal water,inflammation,biomarker,inflammatory disease
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: 131531

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual participant data for all primary and secondary outcome measures will be made available.
• IPD Sharing Time Frame: Data will be available within 6 month of study completion.
• IPD Sharing Access Criteria: Requests will be reviewed and requestors will be required to sign a Data Access Agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No