Multicentre International Study for the Prevention with iAluRil of Radio-induced Cystitis (MISTIC): A Randomised Controlled Study

Abstract

Background Radiation-induced cystitis is a common side effect of radiotherapy (RT) to the pelvic area. Hyaluronic acid (HA) and chondroitin sulfate (CS) are components of the urothelial mucosa and positive results have been obtained for intravesical HA/CS instillations for the treatment of urinary tract infections and bladder pain syndrome. HA/CS may also have a protective effect against RT bladder toxicity. Objective To investigate whether HA and CS protect the urothelium during RT, alleviate lower urinary tract symptoms, and improve quality of life. Design, setting, and participants This multicentre randomised controlled trial was conducted across seven centres in four countries. Male patients aged ≥18 yr scheduled to undergo primary intensity-modulated radiotherapy for localised prostate cancer were enrolled. Intervention Patients were randomised to intravesical HA/CS plus an oral formulation of curcumin, quercetin, HA, and CS (group A) or no treatment (group B). Outcome measurements and statistical analysis The primary endpoint was absolute changes from baseline to follow-up in urinary domain scores for the Expanded Prostate Cancer Index Composite (EPIC), the International Consultation on Incontinence Questionnaire-Male Lower Urinary Tract Symptoms (ICIQ-MLUTS), and the EuroQol Group EQ-5D-5L questionnaire. Data analysis for efficacy and safety outcomes was performed using an intention-to-treat (ITT) approach; the ITT population was defined as all randomised patients. Results and limitations Of 57 patients screened, 49 were enrolled and randomly assigned to either active treatment (group A, n = 25) or the control (group B, n = 24). Three patients in the control group withdrew after randomisation. Changes from baseline to 12 mo were worse in the control group for subtotal scores for urinary symptoms and impact of symptoms on quality of life and for the total score ( p = 0.05, p = 0.003, and p = 0.008, respectively). There was a significant time × group interaction in favour of active treatment for the incontinence symptom score ( p = 0.011) and bother score ( p = 0.017). The absence of a sham procedure and/or placebo is the main limitation. Conclusions Our results suggest that intravesical HA/CS in combination with an oral formulation may reduce urinary symptoms and improve QoL at short-term (1 yr) follow-up. Patient summary We investigated whether hyaluronic acid (HA) and chondroitin sulfate (CS) have a protective effect against the bladder toxicity of radiotherapy for prostate cancer. HA/CS used for weekly bladder irrigation for 6 wk and given orally with curcumin and quercetin for 12 wk reduced urinary i...

Oral Preparation of Hyaluronic Acid, Chondroitin Sulfate, Curcumin, and Quercetin (Ialuril® Soft Gels) for the Prevention of LUTS after Intravesical Chemotherapy

“…Moreover, we reported no AE specifically related to the supplement. Our findings are consistent with those reported in the small randomized controlled trial (RCT) without placebo by Redorta et al The authors showed that intravesical HA/CS plus the oral administration of HA, CS, curcumin, and quercetin was associated with reduced bladder toxicity in patients undergoing radiotherapy for prostate cancer [ 23 ]. The composition, dosage, and hypothesized mechanism of action of Ialuril ® Soft Gels components are summarized in Table 6 .…”

Role of Turmeric and Curcumin in Prevention and Treatment of Chronic Diseases: Lessons Learned from Clinical Trials

“…This study also showed no adverse side effects associated with curcumin . A multicenter international randomized study showed that 200 mg/day curcumin along with chondroitin sulfate, hyaluronic acid, and quercetin, reduced urinary incontinence and improved QoL in patients with prostate cancer undergoing RT . In addition, Meriva, the lecithinized and bioavailable form of curcumin, administered at 200 mg/day of curcumin, with standard therapy for 24 weeks in prostatic hyperplasia, showed no adverse effects, improved QoL, reduced signs and symptoms of hyperplasia, and decreased infections and urinary block .…”

Effects of hyaluronic acid and chondroitin sulfate on acute radiation proctitis in rats

“…[ 7 ] HA/CS is thought to benefit RT bladder toxicity with a protective therapeutic effect on the bladder. [ 8 , 9 ] Therefore, the aim of this study is to determine whether the HA/CS used in radiation cystitis is also effective in ARP.…”