Clinical trial NCT04275206: The Anti-inflammatory Effects of Harkány Medicinal Water
Official title: The Anti-inflammatory Effects of Harkány Medicinal Water
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Rheumatoid Arthritis
Psoriasis
Keywords: medicinal water,inflammation,biomarker,inflammatory disease
Lead sponsor: University of Pecs
Sponsor class: OTHER
Collaborators: name: National Research, Development and Innovation Office, Hungary
name: Harkány Spa Hospital, Hungary
First posted: 2020-02-19
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Dermatology Life Quality Index (DLQI)
timeFrame: baseline (on admission)
measure: Functional Independence Measure (FIM)
timeFrame: baseline (on admission)
measure: SF-36
timeFrame: baseline (on admission)
measure: Patient Uncertainty Questionnaire-Rheumatology (PUQ-R)
timeFrame: baseline (on admission)
measure: Psoriasis Area Severity Index (PASI)
timeFrame: baseline (on admission)
measure: Disease Activity Score Calculator for Rheumatoid Arthritis (DAS 28)
timeFrame: baseline (on admission)
measure: White blood cell count (Routine laboratory parameter)
timeFrame: baseline (on admission)
measure: Haemoglobin (Routine laboratory parameter)
timeFrame: baseline (on admission)
measure: Haematocrit (Routine laboratory parameter)
timeFrame: baseline (on admission)
measure: WE (Routine laboratory parameter)
timeFrame: baseline (on admission)
measure: Creatinine /eGFR/ (Routine laboratory parameter)
timeFrame: baseline (on admission)
measure: Uric acid (Routine laboratory parameter)
timeFrame: baseline (on admission)
measure: High sensitivity C-reactive protein (hs-CRP)
timeFrame: baseline (on admission)
measure: Asymmetric dimethylarginine (ADMA)
timeFrame: baseline (on admission)
measure: Total antioxidant capacity (TAC)
timeFrame: baseline (on admission)
measure: Malondialdehyde (MDA)
timeFrame: baseline (on admission)
Secondary outcomes:
measure: Dermatology Life Quality Index (DLQI)
timeFrame: 3 weeks (before discharge)
measure: Functional Independence Measure (FIM)
timeFrame: 3 weeks (before discharge)
measure: SF-36
timeFrame: 3 weeks (before discharge)
measure: Patient Uncertainty Questionnaire-Rheumatology (PUQ-R)
timeFrame: 3 weeks (before discharge)
measure: Psoriasis Area Severity Index (PASI)
timeFrame: 3 weeks (before discharge)
measure: Disease Activity Score Calculator for Rheumatoid Arthritis (DAS 28)
timeFrame: 3 weeks (before discharge)
measure: White blood cell count (Routine laboratory parameter)
timeFrame: 3 weeks (before discharge)
measure: WE (Routine laboratory parameter)
timeFrame: 3 weeks (before discharge)
measure: Creatinine /eGFR/ (Routine laboratory parameter)
timeFrame: 3 weeks (before discharge)
measure: Uric acid (Routine laboratory parameter)
timeFrame: 3 weeks (before discharge)
measure: High sensitivity C-reactive protein (hs-CRP)
timeFrame: 3 weeks (before discharge)
measure: Asymmetric dimethylarginine (ADMA)
timeFrame: 3 weeks (before discharge)
measure: Total antioxidant capacity (TAC)
timeFrame: 3 weeks (before discharge)
measure: Malondialdehyde (MDA)
timeFrame: 3 weeks (before discharge)
Other outcomes:
Locations:
city: Pécs
country: Hungary
facility: Katalin Dr Szendi
state: Baranya
Study officials:
affiliation: University of Pecs
name: Katalin Dr Szendi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Szendi K, Gerencsér G, Murányi E, Varga Cs. Mutagenic activity of peloids in the Salmonella Ames test. Applied Clay Science 55: 70-74, 2012.
citation: Gerencsér G, Murányi E, Szendi K, Varga Cs. Ecotoxicological studies on Hungarian peloids (medicinal muds). Applied Clay Science 50(1): 47-50, 2010.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.