Table 3.
First Author Year of Publication |
Trial Design | Patient Number Indication |
Dose | Type of Exposure Frequency Duration |
Endpoints and Timepoints | Most Important Findings | Ref. |
---|---|---|---|---|---|---|---|
Franke et al., 2000 | Prospective; blinded; randomized |
60 patients RA |
Radon group: 1.3 kBq/L, 1.6 g/L CO2 Placebo group: 1.6 g/L CO2 |
Bath 20 min 15 times 4 weeks T = 35 °C Additional: Physiotherapy Occupational therapy Galvanic bathes (3/week) Classic massage |
Endpoints: Pain intensity (VAS) Keitel functional Test (KFI) Arthritis Impact Measurement (AIMS) Timepoints: Before and directly after therapy, as well as, 3 and 6 months after therapy. |
Pain intensity decreased in both groups, radon treatment results in a significant and longer lasting benefit from pain relief; KFI more in radon group; AIMS score was significantly increased in radon treated patients up to 6 months; KFI score shows a not significant benefit in radon treated patients |
[98] |
Van Tubergen et al., 2001 | Prospective; different treatment groups at different places. |
120 patients AS (40 spa with radon, 40 spa w/o radon 40 physical therapy at home) |
Radon group: 0.536 WLM Placebo group: Thermal water + sauna Hydrotherapy Bathing Sports |
Gallery/ inhalation Each 1 h 16 times 3 weeks T = 38–41 °C Additional: Physical exercise Postural correction therapy |
Endpoints: BASFI Well-being VAS Pain intensity VAS Morning stiffness Timepoints: Before therapy After therapy week 4, 16, 28, and 40 |
Primary goals borderline significant; pooled index of change shows highly significant differences as well as long-lasting effects of radon compared to conventional treatment |
[105] |
Yamaoka et al., 2004 | Prospective | 15 people (putative healthy individuals) |
Radon group: 2080 Bq/m3 Sauna Group: 54 Bq/m3 Control Group: 54 Bq/m3 |
Inhalation 40 min 5 times TRadon = 36 °C TSauna = 48 °C TControl = 36 °C |
Endpoints: SOD AOC lipid metabolism CD4/CD8 immune cells vasoactive substances diabetes-associated markers Timepoints: Blood draw before and at 2 h after each treatment. In addition, 5 and 10 days after treatment. |
Significant increase in SOD as well as decrease of lipid metabolism and cholesterol at 10 days for radon and sauna group; radon enhances T cell activity significantly, while sauna has similar effects, only significant at 10 days after treatment; radon enhances the CD4 T cell amount significantly after treatment, while CD8 T cells were decreased, respectively; radon group shows significantly more endorphin and a reduced vasopression |
[112] |
Yamaoka et al., 2004 | Prospective | 20 patients OA |
Radon group: 2080 Bq/m3 non-controlled |
Inhalation 40 min each Every 2 days T = 42 °C |
Endpoints: SOD, catalase, lipid peroxide, total cholesterol, GSH, β-endorphin, ACTH, uric acid, ANP, and vasopressin levels in blood Timepoints: Before therapy, 2 h, 2, 4 and 6 weeks after therapy |
SOD activity is significantly and long-lasting increased; Catalase activity is significantly increased after 4 and 6 weeks; T cells of CD4 type are increased, while CD8 T cells are decreased from 2 to 4 weeks after therapy; β-endorphin and anti-ANP levels were significantly and long-lasting increased after therapy; Vasopressin was significantly and long-lasting decreased; Cholesterol and lipid peroxide levels were significantly and long-lasting decreased |
[113] |
Shehata et al., 2006 | Retrospective | 83 patients AS (radon treatment) 10 patients AS (conv. Treatment) 10 patients LBP |
Radon group: ~4.5 nCi/l Placebo groups: Convent. Therapy |
Gallery/ inhalation 1 h each T = 38–41 °C 9–12 times 3–4 weeks Additional: Physiotherapy Hydrotherapy Massage Exercises |
Endpoint: TGF-β (total and active form) Timepoint: Before, during and after the treatment (~0, 2 and 4 weeks)- |
Total TGF-β level increased significantly in radon exposed patients compared to conventional treated patients or LBP controls; active TGF-β increased strongly and significantly in radon exposed patients compared to conventional treated patients or LBP controls; therapy responders show an inverse correlation with CRP concentration |
[107] |
Franke et al., 2007 | Prospective; blinded; randomized |
134 patients RA (67 patients per group) |
Radon group: 1.1 kBq/L, 1.3 g/L CO2 Placebo group: 1.6 g/L CO2 |
Baths 20 min 15 times 3 weeks T = 35 °C Additional: Physiotherapy Occupational therapy Galvanic bathes (3/week) Swedish massage |
Endpoints: pain intensity, pain frequency, morning stiffness, functional capacity (all VAS), Drug intake Timepoints: Before and after last treatment, 3, 6, 9, and 12 months after treatment |
Drug intake was significantly reduced from month 9 on; both groups had treatment effects, most not significant; repeated measurement ANCOVA revealed significant and long-lasting enhanced quality of life due to fewer limitations induced by pain |
[99] |
Moder et al., 2010 | Prospective | 33 AS patients |
Radon group: ~4.5 nCi/L non-controlled |
Gallery/ inhalation 90 min each 10 times 3 weeks 37–40.5 °C |
Endpoints: Disease activity, BASDAI. BASFI, BASMI serum concentration of RANKL, OPG, TNFα, TGF-β, IL-17, IL-6 Timepoints: Before and after therapy (3 weeks) |
Disease-associated scores BASDAI. BASFI, BASMI decreased significantly after therapy; serum conc. of TGF-β1, IL-6, TNF-α, RANKL, OPG, as well as OPG/RANKL ratio was significantly increased; active form of TGF-β, IL-6, TNFα. |
[106] |
Franke et al., 2013 (IMuRa Trial) |
Prospective; blinded; randomized; multicentric |
652 Patients BP 437 pts. OA 230 pts. RA 98 pts. AS 39 pts. Multi 146 pts. |
Radon group (332 patients) Radon bathes according to specific center (with or without CO2) or Radon Speleotherapy Control group: (320 patients) Placebo bathes according to specific center (either tap water or non-radon-containing fountain, with or without CO2) |
Bath 20 min 12 times 3–4 weeks T = 36–38 °C |
Endpoints: Pain intensity (VAS) Pain Questionnaire Functional capacity (FFbH) Western Ontario questionnaire (WOMAC) Health assessment questionnaire (HAQ) BASFI Drug intake Timepoints: Before and after last treatment, 3, 6, and 9 month after treatment |
Radon treatment leading to significant and long-lasting relieve of self-assessed pain (VAS); OA and BP patients have the strongest and most lasting benefit from radon treatment, while OA patients seem to additionally have an enhanced quality of living up to 6 months after treatment |
[76] |
Dischereit et al., 2014 (Article in german) | Prospective | 24 patients RA 24 patients OA |
Radon group 44 kBq/m3 non-controlled |
Gallery/ inhalation 60 min each 12 times 3 weeks T = 37.5–41 °C |
Endpoints: Pain intensity and duration Disease activity and functional score (BASDAI; BAS-G) Serum levels of RANKL, OPG, and TNF-α Timepoints: Directly before and after therapy, as well as 3 months after therapy |
Pain was relieved after therapy and after 3 months in AS patients and after 3 months in OA patients; BASDAI was reduced significantly, and long-lasting in AS patients; TNF-α level was decreased in both groups, significantly in OA; RANKL level was significantly decreased in both groups, OPG increased only in AS; RANKL/OPG ratio decreased only AS significantly |
[108] |
Winklmayr et al., 2015 | Prospective; blinded; randomized |
64 healthy individuals Married partners |
Radon group 412–900 Bq/L, Placebo: thermal water |
Bath 20 min 5 times + 3 times brush up T = 36–39 °C Additional: Mountain hiking 3–4 h daily |
Endpoints: Serum conc. OPG, RANKL, OPG/RANKL ratio Timepoints: Day 0, 6, 60, and 63 and 6 months after last treatment |
Treatment benefits were seen in both groups in OPG, RANKL, and OPG/RANKL ratio; detected borderline significant trend towards bigger effect in Radon treated group |
[114] |
Lange et al., 2016 and 2012 | Prospective | 25 patients RA 24 patients OA |
Radon group 4.5 nCi/l non-controlled |
Gallery/ inhalation 60 min each 12 times 3 weeks T = 37.5–41 °C |
Endpoints: serum conc. RANKL, OPG, TNF-α, and ACPA Timepoints: Directly before and after therapy |
The serum conc. of TNFα and RANKL levels decreased in both groups; only in RA patients, OPG level increased, leading to a decreased RANKL/OPG ratio; ACPA titers decreased only in RA patients |
[115,116] |
Lange et al., 2017 |
Endpoints: Pain VAS FFbH questionnaire ESR Serum CRP, RANKL, OPG, TNF-α, IL-10, and ACPA Timepoints: Directly before and after therapy, as well as 3 months after therapy |
RA patients have significant immediate and lasting effect in pain relief, while health status (FFbH) is increasing; OA patients have significantly lasting pain relief effect; serum concentration of IL-10 is significantly increased directly after treatment in RA patients |
[117] | ||||
Rühle et al., 2017 (RAD-ON01) | Prospective Blinded Randomized |
100 patients with musculoskeletal disorders 50 patients per group Ambulant patients |
Radon group 1200 Bq/L, Radon water only group); Radon/CO2 group 600 Bq/L and 1 g/l CO2; Radon-CO2-group Covered bath-tube |
Bath 20 min each 9 times 3 weeks T = 35 °C |
Endpoints: Immune modulation via DIoB [100] method Pain relief (VAS and questionnaire) Pain sensitivity (dolorimetry, pressure point measurement) Timepoints: Directly before as well as 6, 12, and 30 weeks after therapy |
Long-lasting and significant pain reduction until end of observation period in whole trial population; significant and long-lasting increase in T cells and monocytes; significant temporarily increase of dendritic cells and regulatory T cells; significant and long-lasting reduction of the expression of the activation marker CD69 on T, B, and NK cells |
[104] |
Cucu et al., 2017 (RAD-ON01) |
Endpoints: Amount of regulatory T cells Serum markers of bone and lipid metabolism |
significant and long-lasting decrease of collagen fragments (CTX-I) and reduced levels of visfatin. Both factors are correlating significantly with pain intensity (VAS); regulatory T cells increase significantly and long-lasting after treatment |
[102] | ||||
Rühle et al., 2018 (RAD-ON01) |
Endpoints: Pain relief (VAS and questionnaire) Pain sensitivity (dolorimetry, pressure point measurement) Blood pressure Antioxidative capacity (AOC) Superoxiddismutase (SOD) |
Long-lasting and significant pain reduction until the end of the observation period in whole trial population, Radon CO2 bathes show a trend to be less effective (n.s.); lowered blood pressure in both groups, nightly measured systolic and diastolic blood pressure significantly decreased in Radon/CO2 treated patients; SD-VLF decreased significantly after radon therapy; SOD2 reduced significantly 6 weeks after treatment and increased significantly long-lasting |
[103] | ||||
Kullmann et al., 2018 (RAD-ON01) |
Endpoints: Detection of inflammatory and anti-inflammatory cytokines in serum of patients. |
No significant effects found for TNFα, IL-1β, IFNγ, IL-18, IL-1Ra, IL-10 concentration in serum of the patients; TGF-β concentration was significantly increased after treatment and significantly correlates with pain sensitivity; IL-18 level corresponds with lowered pain perception |
[101] |
Abbreviations: ACPA: anti-citrullinated peptide antibodies; ACTH: adrenocorticotropic hormone; ACTH: Adrenocorticotropine; AIMS: arthritis impact measurement score; ANP: atrial natriuretic polypeptide; AOC: Antioxidative Capacity; AS: ankylosing spondylitis; BAG-G: Bath Ankylosing Spondylitis Patient Global Score; BALF: bronchioalvelolar lavage fluid; BASDAI: Bath Ankylosing Spondylitis Disease Activity Index; BASFI: Bath Ankylosing Spondylitis Functional Index; BASMI: Bath Ankylosing Spondylitis Metrology Index; BP: Back Pain; CD: cluster of differentiation; CO2: carbon dioxide; CRP: c-reactive protein; CTX: Cross Laps; FFbH: Funktions Fragebogen Hannover (Functional Capacity); GSH: Glutathione; HAQ: Health assessment questionnaire; IFN: interferon; IL: interleukin; KFI: Keitel functional index; LBP: lower back pain; OA: Osteoarthritis; OPG: osteoprotegerin; RA: rheumatoid arthritis; RANKL: receptor activator of NFkB Ligand; SOD: superoxide dismutase; TGF: transforming growth factor; TNF: tumor necrosis factor; VAS: Visual Analog Scale; WOMAC: Western Ontario questionnaire. Bold letters highlight the trial groups, additional treatments, trial endpoints, and timepoints of investigation.