title: Effect of intravesical glycosaminoglycan substitution therapy on bladder pain syndrome/interstitial cystitis, bladder capacity and potassium sensitivity Alkalinized lidocaine and heparin provide immediate relief of pain and urgency in patients with interstitial cystitis. A combined intravesical therapy with hyaluronic acid and chondroitin for refractory painful bladder syndrome/interstitial cystitis [Treatment of overactive bladder with sodium chondroitin sulphate]. Intravesical hyaluronic acid in the treatment of refractory interstitial cystitis. Prophylactic vesical instillations with 0.2% chondroitin sulfate may reduce symptoms of acute radiation cystitis in patients undergoing radiotherapy for gynecological malignancies Intravesical hyaluronic acid for interstitial cystitis/painful bladder syndrome: a comparative randomized assessment of different regimens. Intravesical alkalinized lidocaine (PSD597) offers sustained relief from symptoms of interstitial cystitis and painful bladder syndrome Comparative assessment of maximal bladder capacity, 0.9% NaCl versus 0.2 M Kcl, for the diagnosis of interstitial cystitis: a prospective controlled study. Successful downregulation of bladder sensory nerves with combination of heparin and alkalinized lidocaine in patients with interstitial cystitis. [Follow-up at 24 months after treatment of overactive bladder with 0.2 % sodium chondroitin sulfate]. Intravesical hyaluronic acid and alkalinized lidocaine for the treatment of severe painful bladder syndrome/interstitial cystitis Results of endovesical hyaluronic acid/chondroitin sulfate in the treatment of Interstitial Cystitis/Painful Bladder Syndrome. Intravesical instillation of hyaluronic acid prolonged the effect of bladder hydrodistention in patients with severe interstitial cystitis. Treatment of interstitial cystitis with Cystistat®, A hyaluronic acid product Impact of intravesical hyaluronic acid and chondroitin sulfate on bladder pain syndrome/interstitial cystitis The potassium sensitivity test: a predictor of treatment response in interstitial cystitis Do cystometric findings predict the results of intravesical hyaluronic acid in women with interstitial cystitis?
abstract: Objective . To evaluate changes in bladder capacity and potassium sensitivity after glycosaminoglycan ( GAG ) substitution therapy . Material and methods . The study population comprised two groups of female patients with bladder pain syndrome/interstitial cystitis ( BPS/IC ) : responders ( those with symptom improvement ) and non-responders ( those without symptom improvement ) after a 10-week period of intravesical , episodic , weekly , GAG substitution therapy . A total of 27 volunteers with increased pre-therapeutic potassium sensitivity were enrolled in the study and re-evaluated using the modified comparative potassium test ( maximal bladder capacity with a saline solution versus a 0.2 M KCl solution ) following intravesical GAG substitution therapy . Results . In the 13 responders , the average maximal bladder capacity increased by 17 % with the saline solution and by 101.5 % with the 0.2 M KCl solution . In the 14 non-responders , post-therapeutic average maximal bladder capacity was decreased by 35 % with the saline solution and remained relatively unchanged after instillation with a 0.2 M KCl solution . Conclusion . These data demonstrate that in patients who respond symptomatically to intravesical GAG substitution therapy , cystometric bladder capacity is increased , whereas non-responders experience a decrease in bladder capacity INTRODUCTION It has been reported in an open-label study that the combination of alkalinized lidocaine and heparin can immediately relieve the symptoms of urinary urgency , frequency , and pain associated with interstitial cystitis ( IC ) . This combination has also been reported to relieve pain associated with sex in patients with IC . AIM The aim of this study was to corroborate these findings in a multicenter setting . METHODS The study design was a multicenter prospect i ve , double-blind , crossover , placebo-controlled trial . Each participant met all of the clinical National Institute of Diabetes and Digestive and Kidney Diseases criteria ( excluding cystoscopy ) for IC . Each patient received drug and control , in r and om order , within 48 hours of enrolling in the study . MAIN OUTCOME MEASURES The primary outcome measure was percent change in pain score ( 11-point analog pain scale ) 12 hours after receiving the drug or control . Secondary measures were the global assessment response ( GAR ) of symptoms and 12-hour average urgency reduction determined from 11-point urgency scales . RESULTS Eighteen ( 18 ) patients completed the trial . The average reduction of pain over 12 hours was 21 % for control and 42 % for active drug ( P = 0.0363 ) . GAR was 13 % for control and 50 % for drug ( P = 0.0137 ) . Average urgency reduction was 13 % for control and 35 % for drug ( P = 0.0328 ) . CONCLUSIONS The combination of alkalinized lidocaine and heparin provides up to 12 hours of relief from urgency and pain associated with IC . This combination provides significant immediate relief of symptoms for patients with IC The aims of this study were to evaluate the efficacy and tolerability of intravesical instillations of high-molecular-weight hyaluronic acid ( HA ) 1.6 % and chondroitin sulfate ( CS ) 2.0 % in patients with refractory painful bladder syndrome/interstitial cystitis ( PBS/IC ) and to observe their impact on Quality of Life . Twenty-three women were enrolled . They received bladder instillations with HA and CS weekly for 20 weeks and then monthly for 3 months . Mean follow-up after completion of therapy was 5 months . We observed a significant improvement in urinary symptoms on voiding diaries and Visual Analogue Scale for frequency ( p = 0.045 ) , urgency ( p = 0.005 ) , and pain ( p = 0.001 ) . The O’Leary – Sant Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index result ed in a significant improvement in both scores ( p = 0.004 and 0.01 , respectively ) . The Pelvic Pain and Urgency/Frequency Symptom Scale only showed significant improvement in the symptom score ( p = 0.001 ) . This promising experience seems to offer an additional therapeutic option in patients with refractory PBS/IC OBJECTIVE It is not always possible to clearly differentiate the symptoms of overactive bladder and interstitial cystitis . A prospect i ve r and omized study was performed to determine whether instillation of sodium chondroitin sulphate for treatment of interstitial cystitis is also effective in treating overactive bladder . The expected benefit of this therapeutic approach in overactive bladder is based on the assumption that the glycosaminoglycan layer may be damaged in overactive bladder as well . MATERIAL AND METHODS Patients with chronic overactive bladder were r and omized to one of two study groups each including 41 patients . Group A was treated with an anticholinergic agent ( tolterodine ) , group B with sodium chondroitin sulphate ( Uropol S ) . The diagnosis was established on the basis of a gynecologic examination and history , urodynamic testing , introital ultrasound , and cystoscopy . Patients were treated for 12 months . RESULTS An improvement of symptoms was reported by 15/35 ( 43 % ) of the patients in group A ( p = 0.000 ) as compared with 23/32 ( 72 % ) of the patients in group B. The subjective outcome was corroborated by means of urodynamic testing , number of pads used , voiding frequency , and nycturia ( voiding diary ) . Quality of life increased significantly in both groups in the course of treatment but there was no significant difference between both groups . CONCLUSION The results of the study presented here suggest that restoring the glycosaminoglycan layer also improves or cures the symptoms in patients with overactive bladder . Patients clearly benefit from instillation of sodium chondroitin sulphate . These results must be confirmed in larger studies before a wider use of this therapeutic option can be recommended PURPOSE Based on the assumption that interstitial cystitis results from a defective mucous lining of the bladder epithelium , we investigated the activity of hyaluronic acid in the treatment of this disease . Hyaluronic acid is an important glycosaminoglycan present in all connective tissues , including the glycosaminoglycan layer of the vesical mucosa . It exhibits a variety of pharmacological properties that enhance its appeal for the therapy of interstitial cystitis . MATERIAL S AND METHODS A total of 25 patients with characteristic findings of interstitial cystitis refractory to other medical treatments participated in a trial of intravesical hyaluronic acid at a dose of 40 mg . weekly for 4 weeks and then monthly . Response to therapy was evaluated by symptom score , voiding diaries and visual analog scales . RESULTS An initial 56 % positive ( complete plus partial ) response rate at week 4 increased to 71 % by week 12 and response was maintained until week 20 . Beyond week 24 there was a moderate decrease in the effectiveness of the medication . There was no significant toxicity attributable to hyaluronic acid in the bladder . CONCLUSIONS The response of patients with refractory interstitial cystitis to the intravesical administration of hyaluronic acid was gratifying . In the past many therapies for interstitial cystitis which were initially considered promising failed the test of a controlled study . Such a study to determine the activity of hyaluronic acid in patients with interstitial cystitis is currently under way Introduction and hypothesisWe studied the feasibility and efficacy of intravesical instillations with 40 ml chondroitin sulfate 0.2 % solution to prevent or reduce acute radiation cystitis in women undergoing pelvic radiotherapy . Methods In a comparative pilot study in 20 patients , half of the patients received instillations . Instillations ' bother was measured with visual analog scores ( VAS , 0–10 ) ; bladder pain , with VAS ; micturition-related quality of life , with the urogenital distress inventory ( UDI ) . Results One of the instilled patients discontinued the instillations . The first median “ acceptability”-VAS was 0 ( range , 0–3 ) ; the last median was 1 ( range , 0–3 ) . “ Bladder pain”-VAS peaked halfway in the treatment among controls ( median , 1 ; range , 0–5 ) and after treatment in the instilled patients ( median , 1 ; range , 1–3 ) . UDI scores showed over time median follow-up scores at or above median baseline scores in controls and at or below median baseline scores in instilled patients . Conclusion Intravesical instillations with chondroitin sulfate 0.2 % solution may decrease the bother related to bladder symptoms and are well tolerated OBJECTIVES To compare the clinical effectiveness of different regimens of intravesical hyaluronic acid instillation for patients with interstitial cystitis/painful bladder syndrome . METHODS A total of 60 patients ( age 16 - 77 years ) diagnosed with interstitial cystitis/painful bladder syndrome were enrolled in this prospect i ve , r and omized study . A total of 30 patients were assigned to receive four weekly intravesical instillations of 40 mg of hyaluronic acid followed by five monthly instillations ( hyaluronic acid-9 group ) . Another 30 patients received 12 intravesical instillations of 40 mg hyaluronic acid every 2 weeks ( hyaluronic acid-12 group ) . Symptomatic changes after hyaluronic acid treatments were assessed using Interstitial Cystitis Symptom and Problem Indexes , pain visual analog scale , functional bladder capacity , frequency and nocturia in voiding diary , maximum flow rate , voided volume , postvoid residual volume , and Quality of Life Index at 1 , 3 and 6 months . RESULTS Of the 60 patients , 59 were evaluable at the end of the study . The Interstitial Cystitis Symptom Index , Interstitial Cystitis Problem Index and total score , pain visual analog scale , functional bladder capacity , maximum flow rate , and Quality of Life Index improved significantly after 6 months in both groups . The frequency and voided volume improved significantly only in the hyaluronic acid-12 group . However , patients with moderate and marked improvement were clinical ly similar in both groups . The measured variables did not differ between the two groups over the course of the study . CONCLUSION No significant difference was noted in the therapeutic effect between two hyaluronic acid instillation regimens for treatment of interstitial cystitis/painful bladder syndrome patients . Both groups showed significant improvement in symptom scores and Quality of Life Index To assess the immediate and sustained relief of the symptoms of interstitial cystitis/painful bladder syndrome ( IC/PBlS ) after a consecutive 5‐day course of treatment with intravesical alkalinized lidocaine ( PSD597 ) , and to characterize the pharmacokinetics of single and multiple doses of intravesical PSD597 in a subgroup of patients PURPOSE Increased urothelial permeability has been proposed as a cause of interstitial cystitis ( IC ) . The potassium sensitivity test assesses bladder discomfort after instillation of 0.4 M KCl for identification of increased urothelial permeability . Since exposure to 0.4 M KCl may be extremely painful for patients with IC we investigated a less traumatic alternative . MATERIAL S AND METHODS The study comprised 38 controls and 40 patients with IC . In all subjects cystometry was performed with 0.9 % NaCl followed by 0.2 M KCl , and filling volume at first urge and maximum bladder capacity ( Cmax ) were assessed for both solutions . RESULTS Controls did not show a significant change in Cmax . KCl decreased Cmax in 37 of 40 ( 92 % ) patients with IC with a mean decrease of 30 % . The examination was painless in all controls and in 33 of 40 ( 82 % ) patients with IC , and was moderately painful in 7 . CONCLUSIONS For demonstration of increased potassium sensitivity and diagnosis of IC , comparative assessment of Cmax is a well tolerated alternative to the 0.4 M potassium sensitivity test . Statistical evaluation of these results suggests that a decrease in Cmax greater than 30 % is indicative of IC OBJECTIVES To test the efficacy of a new intravesical therapeutic solution in relieving urgency/frequency and pain in interstitial cystitis ( IC ) . METHODS A solution of 40,000 U heparin , 8 mL 1 % lidocaine ( 80 mg ; group 1 ) or 2 % lidocaine ( 160 mg ; group 2 ) , and 3 mL 8.4 % sodium bicarbonate was administered intravesically in patients with newly diagnosed IC with significant frequency , urgency , and pain . Using the Patient Overall Rating of Improvement of Symptoms , the response to treatment was evaluated within 20 minutes of instillation in all patients , after 24 to 48 hours in group 2 , and after three treatments per week for 2 weeks in group 2 patients who elected to receive additional instillations . Significant symptom relief was defined as 50 % or greater symptom improvement . RESULTS After one instillation , 35 ( 75 % ) of 47 patients in group 1 ( 1 % lidocaine ) and 33 ( 94 % ) of 35 in group 2 ( 2 % lidocaine ) reported significant immediate symptom relief . The difference in the response rates was statistically significant ( P < 0.01 ) . In group 2 , 50 % of the subjects experienced at least 4 hours of symptom relief from the single instillation , and 16 ( 80 % ) of 20 reported significant sustained symptom relief after 2 weeks of treatment . CONCLUSIONS Intravesical treatment with combined heparin and alkalinized lidocaine immediately reduced the pain and urgency of IC in most patients treated for newly diagnosed IC . Symptom relief lasted beyond the duration of the local anesthetic activity of lidocaine , suggesting the solution suppresses neurologic upregulation . In IC treatment , this new intravesical solution may be helpful in the interval before heparinoid therapy reaches its full effect AIM A retrospective study was performed to investigate whether the improvement of symptoms achieved with 0.2 % sodium chondroitin sulfate in treating overactive bladder ( OAB ) persists after 24 months . MATERIAL S AND METHODS Two years ago , a total of 82 patients with chronic OAB were r and omly assigned to receive either anticholinergic treatment ( Tolterodin ; group A , n = 41 ) or 0.2 % sodium chondroitin sulfate ( Gepan instill ; group B , n = 41 ) . Diagnostic assessment included a gynecological examination and history , urodynamic test-ing , introital ultrasound , and cystoscopy .  Duration of treatment was 12 months . The patients underwent repeat follow-up after 24 months and the findings were compared with the results at 12 months . RESULTS In group A , 15 / 35 ( 43 % ) women reported an improvement of symptoms after 12 months as opposed to only 5 / 35 ( 14 % ) after 24 months . In group B , there was an improvement in 23 / 32 ( 72 % ) at 12 months and in 18 / 32 ( 56 % ) after 24 months ( p = 0.001 ) . The subjective results were corroborated by means of urodynamic test-ing , pad counts , voiding frequency and nycturia ( voiding diary ) . CONCLUSION Our findings suggest that instillation treatment with 0.2 % sodium chondroitin sulfate results in a more sustained improvement or cure of the symptoms of overactive bladder due to development of a glycosaminoglycan layer . Long-term results are needed for confirmation Introduction and hypothesisIntravesical instillation of hyaluronic acid ( HA ) may restore the integrity of glycosaminoglycan layer in patients with painful bladder syndrome/interstitial cystitis ( PBS/IC ) , and the benefit may be improved with addition of alkalinized lidocaine ( AL ) . Methods 48 women with severe PBS/IC who failed oral medications were enrolled and divided into one trial and two control groups . The trial group received intravesical 40 mg HA , 10 ml of 2 % lidocaine and 5 ml of 8.4 % sodium bicarbonate on a weekly basis for 8 weeks and then monthly for 4 months with a subsequent follow-up of 24 weeks , while the two control groups received 40 mg HA and mixture of 10 ml of 2 % lidocaine and 5 ml of 8.4%sodium bicarbonate respectively following the same procedure . Response to therapy was evaluated by Global Response Assessment , voids per day , Visual Analogue Scale for pain , frequency and urgency , O’leary-Sant Interstitial Cystitis Symptom Index and Problem Index , cystoscopy and bladder capacity . Results Overall 45 patients finished this study protocol . The HA + AL group and the AL group showed significant improvement at week 2 ( P < 0.01 ) , while the HA group began to show effect at week 4 ( P < 0.01 ) . There was no improvement in the AL group at week 24 and these patients quitted the study without follow up . Contrarily , the HA + AL and HA group kept on improving till the end of the study without significant difference between the two groups . Conclusions Intravesical instillation of HA and AL may provide both immediate and sustained relief of symptoms in severe PBS/IC in this preliminary study OBJECTIVES The aim of our study was to test the effect of a more viscous compound than existent hyaluronic acid formulation in helping to restore a defective glycosaminoglycan layer , and therefore in improving Interstitial Cystitis/Painful Bladder Syndrome ( IC/PBS ) symptoms when administered intravesically in IC/PBS patients . METHODS A total of 23 female patients completed the study . Patients received endovesical administration of hyaluronic acid and chondroitin sulfate in normal saline , 40 ml , weekly for 12 weeks and then bi-weekly for 6 months , if there was initial response . RESULTS After 12 weeks treatment both Interstitial Cystitis Symptom and Problem Index ( ICSI/ICPI ) , pelvic pain and Urgency/Frequency Symptom Scale ( PUF ) showed a mean significant improvement , which was maintained thereafter . The average number of voidings and mean voiding volumes revealed significant improvement after the 12 weeks ' treatment period , with a significant reduction and increase , respectively . Mean voiding volume increased from 143 ml to 191 , which apparently was not reflected in a corresponding reduction of number of daily voids ( from 15,5 to 14 ) . VAS values decreased from 5,4 to 3,6 ( pain ) and from 6,0 to 3,5 ( urgency ) after the treatment cycle , showing a significant improvement . CONCLUSIONS In our preliminary experience , the administration of intravesical hyaluronic acid plus chondroitine sulphate appears to be a safe and efficacious method of treatment in IC/PBS OBJECTIVES To evaluate the efficacy of intravesical instillation of hyaluronic acid ( HA ) after hydrodistention for the treatment of patients with interstitial cystitis ( IC ) having small bladder capacity . METHODS A total of 47 patients with IC ( aged 27 - 76 years ) whose functional bladder capacity was less than 200 mL received bladder hydrodistention .  Thereafter , 20 patients received intravesical instillation of 40 mg HA weekly in the first month and then monthly in the following 2 months . Sixteen patients received intravesical heparin instead and 11 patients received hydrodistention alone as the control . Mean voids per day , visual analog scale for pain , and functional bladder capacity were measured before hydrodistention and 3 and 6 months after hydrodistention in all 3 groups and 9 months after hydrodistention in HA and heparin groups . RESULTS Two patients in the HA group and 1 in the heparin group failed to complete the treatment . Three months after hydrodistention , there was no improvement in the control group . Six and 9 months after hydrodistention , rate of improvement was significantly higher in the HA group than in the heparin group ( 77.8 % vs 33.3 % , P < .05 ; 50 % vs 20 % , P < .05 ) . At 9 months , heparin treatment did not show any improvement . Improvement in voids per day ( -1.8 + /- 2.5 , P < .01 ) , visual analog scale ( -0.9 + /- 1.1 , P < .01 ) , and bladder capacity ( 16 + /- 18 mL , P < .01 ) was still significant in the HA group . CONCLUSIONS Intravesical instillation of HA may obviously prolong the effect of bladder hydrodistention in patients with severe IC . Its effect was better than heparin Objective . To determine whether intravesical hyaluronic acid is effective in reducing the urinary frequency and pain associated with interstitial cystitis/painful bladder syndrome ( IC/PBS ) . Material and methods . In a prospect i ve , unblinded , uncontrolled pilot study , 20 patients ( age range 34–80 years ) , all suffering from IC/PBS , received weekly bladder instillations of hyaluronic acid for 1 month and monthly instillations for a further 2 months . Patients were then offered further monthly instillations and all were subsequently evaluated after 3 years . Patient outcomes assessed were urinary frequency , use of analgesics and pain . Results . All patients completed the 3 months of hyaluronic acid treatment with mean decreases in nocturia and pain of 40 % and 30 % , respectively , and a decrease in analgesic use . Thirteen patients ( 65 % ) responded to treatment ( responders ) and continued therapy , while seven patients withdrew , six because of a lack of response and one due to cystectomy . In the 13 patients who continued hyaluronic acid instillations , four complete responders ( 30 % ) ceased therapy after a strong positive response ( 36 % , 60 % and 81 % decreases compared to baseline in day-time voids , night-time voids and pain scores , respectively ) which was maintained in the absence of continuous therapy , while after 3 years seven partial responders ( 35 % ) were still on therapy ( 25 % and 43 % decreases compared to baseline in day-time voids and pain scores , respectively ) . Two patients developed other diseases during follow-up and showed no response to long-term therapy . Hyaluronic acid was well tolerated by all patients . Conclusion . Hyaluronic acid safely reduced the pain and , to a lesser degree , the urinary frequency associated with IC Introduction and hypothesisIntravesical instillations of hyaluronic acid ( HA ) and chondroitin sulfate ( CS ) may lead to regeneration of the damaged glycosaminoglycan layer in interstitial cystitis/bladder pain syndrome ( IC/BPS ) . Methods Twenty-two patients with IC/BPS received intravesical instillations ( 40 ml ) of sodium HA 1.6 % and CS 2.0 % in 0.9 % saline solution ( IALURIL ® , IBSA ) once weekly for 8 weeks , then once every 2 weeks for the next 6 months . Results The score for urgency was reduced from 6.5 to 3.6 ( p = 0.0001 ) , with a reduction in pain scores from an average of 5.6 to 3.2 ( p = 0.0001 ) . The average urine volume increased from 129.7 to 162 ml ( p < 0.0001 ) , with a reduction in the number of voids in 24 h , from 14 to 11.6 ( p < 0.0001 ) . The IC Symptom and Problem Index decreased from 25.7 to 20.3 ( p < 0.0001 ) , and the Pain Urgency Frequency score , from 18.7 to 12.8 ( p < 0.0001 ) . Conclusion The treatment appeared to be effective and well tolerated in IC/BPS in this initial experience To determine whether the potassium sensitivity test ( PST ) can be used to predict the response to treatment with intravesical sodium hyaluronate in patients with interstitial cystitis INTRODUCTION AND OBJECTIVES According to National Institute of Health ( NIH ) criteria , a bladder capacity of less than 350 cc is an automatic exclusion for a diagnosis of Interstitial Cystitis ( IC ) . In the present study , patients , showing symptoms of IC and with bladder capacities of < 350 and > /=350 cc were tested as to their response to a intravesical hyaluronic acid therapy . METHODS The study included 48 patients with clinical symptoms of IC and a positive 0.4 M potassium sensitivity test .  Maximum bladder capacity ( C(max ) ) was assessed for the 0.9 % NaCl solution first and then for the 0.2 M KCl solution . After the NaCl cystometry , patients were separated into two groups : Group I with a C(max ) of < 350 cc and Group II with a C(max ) of > /=350 cc . Both groups were again separated in two further groups as to the respective percentage reduction of C(max ) with the 0.2 M KCl solution : Group Ia/IIa ( > /=30 % ) and Group Ib/IIb ( < 30 % ) . Patients were treated with weekly instillations of 40 mg hyaluronic acid for 10 consecutive weeks . Pre- and post-treatment bladder symptoms were evaluated through their visual analog scale ( VAS ) scores . RESULTS With the saline solution , 32 patients had a C(max ) of < 350 cc ( Group I ) , while 16 patients had a C(max ) of > /=350 cc ( Group II ) . Evaluation of VAS scores confirmed a positive response , i.e. symptom relief , to hyaluronic acid therapy , irrespective of bladder capacity . The improvement was particularly evident in patients with a C(max ) reduction of > /=30 % versus those with a reduction of < 30 % with the 0.2 M KCl solution ( p=0.003 ) . CONCLUSION The present study demonstrates that patients with typical IC symptoms and a cystometric bladder capacity of > /=350 cc , may have increased potassium sensitivity as a sign of IC and show symptom improvement after hyaluronic acid instillation therapy
target: HMW-HA was significantly superior in cost effectiveness and cost efficacy to all other instillation regimes .
background: Bladder pain syndrome/interstitial cystitis ( BPS/IC ) is a chronic disease characterised by persistent irritating micturition symptoms and pain .
  The objective was to compare the clinical efficacy of currently available products for intravesical therapy of BPS/IC and to assess their pharmacoeconomic impact .