Interstitial Cystitis Symptom Score Research Articles

Amniotic bladder therapy: study of micronized amnion/chorion for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS) at 6months.

Intravesical application of birth tissue has been reported to inhibit inflammation, alleviate collagen fiber accumulation, and enhance bladder tissue generation. We have previously reported that intra-detrusor micronized amnion monolayer (AM) injections provide short-term clinical improvement in refractory IC/BPS patients. Herein, we evaluate the therapeutic responses and adverse events of micronized amnion/chorion bilayer (AC) in patients with refractory IC/BPS with 6months follow-up. Fifteen patients affected by IC/BPS who failed conventional therapy received 100mg of reconstituted micronized AC was injected intra-detrusor via cystoscopy under general anesthesia, using a 23-gauge needle. Twenty 0.5-mL injections were administered into the lateral and posterior bladder walls, avoiding the dome and trigone. Changes in interstitial cystitis symptom index (ICSI), Interstitial cystitis problem index (ICPI), Bladder pain/ interstitial cystitis symptom score (BPIC-SS) and Overactive Bladder Assessment Tool (OAB), from baseline to 6months post-injection were evaluated retrospectively.The safety of injections was analyzed. Fifteen total refractory IC/BPS patients with an average age of 41.1 ± 14.5years were included in the study, receiving intra-detrusor injections of 100mg of micronized AC. One month after injections, significant improvement in IC/BPS symptom scores was noted in all patients. All patients maintained a sustained clinical response at 6months post-injection. No product-related adverse events were observed. Our findings indicate that the AC formulation significantly reduces time to symptom relief in patients with refractory interstitial cystitis/bladder pain syndrome (IC/BPS) and maintains a sustained response up to 6months post-injection. These results suggest a promising clinical benefit of using an amnion/chorion bilayer product for treating IC/BPS. Further research is needed to confirm these findings and assess the long-term durability of this treatment approach. This study represents the first evidence supporting the clinical advantages of an amnion/chorion bilayer product in managing IC/BPS.

Early three-month report of amniotic bladder therapy in patients with interstitial cystitis/bladder pain syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by symptomatic frequency and urgency, as well as chronic pelvic pain. Disruption of the urothelial barrier is closely associated with IC/BPS. As amniotic membranes (AM) offer capabilities of wound healing in many other fields of medicine, likewise amniotic bladder therapy (ABT) may offer capability of urothelial healing in IC/BPS. Under general anesthesia, 10 consecutive IC/BPS patients received intra-detrusor injections of 100mg micronized AM (Clarix Flo) diluted in 10ml 0.9% preservative-free sodium chloride. Clinical evaluation and questionnaires (Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS), Overactive Bladder Assessment Tool, and SF-12 Health Survey) were repeated at pre-op and 2, 4, 8 and 12weeks post-op. Ten females (47.4 ± 14.4years) who had recalcitrant IC/BPS for 7.8years (5.2-12.1years) received injection of micronized AM uneventful in all cases. After treatment, voiding symptoms and bladder pain significantly improved from pre-injection to 3months. BPIC-SS significantly decreased from 37.4 ± 0.70 at baseline to 12.2 ± 2.90 at 3months (p < 0.001). This corresponded to a significant improvement in their overall physical and mental quality of life. No adverse events occurred related to micronized AM injections, such as UTIs or acute urinary retention. ABT could be an innovative treatment option for IC/BPS patients in terms of improving clinical symptoms based on preliminary outcomes at 3months. Further studies are warranted to confirm the usefulness of ABT in patients with IC/BPS and to determine the duration of the effect.

A Phase II Study of the Efficacy and Safety of the Novel Oral SHIP1 Activator AQX-1125 in Subjects with Moderate to Severe Interstitial Cystitis/Bladder Pain Syndrome

In this 6-week, randomized, double-blind, placebo controlled, multicenter trial we assessed the effect of the novel SHIP1 (SH2-containing inositol-5'-phosphatase 1) activator AQX-1125 on bladder pain and urinary symptoms in patients with interstitial cystitis/bladder pain syndrome. Women with interstitial cystitis/bladder pain syndrome and a mean pain score of 5 or greater on an 11-point scale despite treatment were randomized to AQX-1125 or placebo orally once daily for 6 weeks. Average and maximum pain scores (daily) and urinary frequency (before visits) were recorded by e-diary and at clinic visits. The O'Leary-Sant ICSI (Interstitial Cystitis Symptom Index) and ICPI (Interstitial Cystitis Problem Index), BPIC-SS (Bladder Pain Interstitial Cystitis Symptom Score) and SF-12v2® questionnaires were administered. Safety was monitored through 6 weeks of treatment and 4 weeks of followup. A total of 37 patients received oral AQX-1125 and 32 received placebo. At 6 weeks average daily pain on an e-diary decreased by 2.4 points for AQX-1125 vs 1.4 for placebo (p = 0.061), while average pain at clinic decreased by 2.6 vs 1.1 (p = 0.008), maximum daily pain on e-diary diary decreased by 2.6 vs 1.4 (p = 0.030) and maximum pain at clinic decreased by 2.8 vs 1.1 (p = 0.028). AQX-1125 reduced ICSI by 3.8 points vs 1.4 for placebo (p = 0.005), ICPI by 3.6points vs 1.6 (p = 0.014) and BPIC-SS by 8.8 points vs 4.0 (p = 0.011). Urinary frequency decreased on AQX-1125 by 3.6 voids per 24 hours vs 0.8 for placebo (p= 0.040). Adverse event rates were similar for AQX-1125 and placebo (51.4% and 78.1%, respectively). No serious adverse events were reported. Women with moderate to severe interstitial cystitis/bladder painsyndrome who were treated with the oral SHIP1 activator AQX-1125 reported significantly reduced bladder pain and improved urinary symptoms at 6weeks. AQX-1125 was well tolerated. AQX-1125 may be a potential new treatment for interstitial cystitis/bladder pain syndrome. It warrants further investigation.

Phenotype-directed Management of Interstitial Cystitis/Bladder Pain Syndrome

To assess a flexible therapeutic strategy for patients referred to a specialized interstitial cystitis/bladder pain syndrome (IC/BPS) clinic using an individualized phenotype-directed treatment plan based on clinically based urinary, psychosocial, organ-specific, infection, neurologic or nonbladder, and tenderness of pelvic floor (UPOINT) categorization, instead of the traditional algorithmic stepwise approach. Consecutive patients referred to a specialized tertiary IC/BPS clinic with at least 1 follow-up posttreatment visit were categorized according to their UPOINT status and treated according to previously published individualized phenotype-based treatment plan. Patients were assessed at baseline and up to 2 years with validated symptom scores (interstitial cystitis symptom score [ICSI]; and pain urgency frequency questionnaire) as well as pain and voiding assessments. Follow-up visit data were available for 93 patients (mean age, 45.2 years; median age, 44 years; mean ICSI, 13.2±3.6). Patients reported a median of 4 UPOINT domains (mean, 3.7±0.94) with the following distribution: U=100%; P=31.2%; O=97.8%; I=45.2%; N=39.8%; and T=55.9%. The mean decrease in ICSI was 3.4 points. Significant clinical improvement (>30% decrease in ICSI) was observed in 46.2% compared with initial baseline visit. Pain urgency frequency, and pain and urgency scoring changes were comparable. No correlation between severity of symptoms and number of domains and ICSI decrease was observed. Almost 50% of patients referred to a tertiary IC/BPS clinic, regardless of the complexity or severity of condition, experienced clinically significant improvement using an individualized phenotype-directed therapeutic approach.

Bladder Pain Syndrome Treated with Triple Therapy with Gabapentin, Amitriptyline, and a Nonsteroidal Anti-Inflammatory Drug

PurposeBladder pain syndrome is a chronic disease that manifests as bladder pain, frequency, nocturia, and urgency. Gabapentin, amitriptyline, and nonsteroidal anti-inflammatory drugs are efficacious treatments for bladder pain syndrome. Here, we assessed the effect of triple therapy with these drugs in women with bladder pain syndrome.MethodsBetween May 2007 and May 2010, we conducted a prospective nonrandomized study on 74 patients with bladder pain syndrome. Of these patients, 38 (11 men and 27 women; mean age, 55.9 years; range, 25 to 77 years; mean follow-up, 12.6 months) were administered the interstitial cystitis (IC) symptom scales (O'Leary-Sant Symptom Index) and visual analog scale (VAS) 1, 3, and 6 months after treatment to assess the efficacy of triple therapy.ResultsThe pretreatment O'Leary-Sant IC symptom score was 11.7, and the post-treatment scores were 4.4, 3.8, and 4.0 at 1, 3, and 6 months, respectively; the pretreatment problem index score was 10.5, and the post-treatment scores were 3.7, 2.7, and 2.9 at 1, 3, and 6 months, respectively. The pretreatment VAS score was 6.7, and the post-treatment scores were 1.8, 1.5, and 1.7 at 1, 3, and 6 months, respectively. The O'Leary-Sant IC symptom index and problem index and VAS scores improved considerably 1 month after treatment (P<0.05). However, the results at 1, 3, and 6 months after treatment were not significantly different (P>0.05).ConclusionsTriple therapy was sufficiently effective in patients with bladder pain syndrome and caused no significant adverse effects. However, large-scale studies should be performed to verify our findings.

A RANDOMIZED DOUBLE-BLIND TRIAL OF ORAL L-ARGININE FOR TREATMENT OF INTERSTITIAL CYSTITIS

Nitric oxide synthase activity is decreased in the urine of patients with interstitial cystitis compared to the urine of controls. In a preliminary trial oral L-arginine, the substrate for nitric oxide synthase, increased urinary nitric oxide synthase activity and improved interstitial cystitis symptoms. This randomized, double-blind, placebo controlled study further investigates the efficacy of L-arginine treatment for interstitial cystitis. A total of 53 interstitial cystitis patients were assigned to receive daily 1,500 mg. L-arginine or placebo orally for 3 months. Interstitial cystitis symptoms were assessed by interviews at 2 weeks, and 1, 2 and 3 months. The trial was completed by 21 of 27 patients in the L-arginine group and 25 of 26 in the placebo group. Using per protocol analysis 29% (6 of 21 patients) in the L-arginine group and 8% (2 of 25) in the placebo group were clinically improved by the end of the trial (p = 0.07). A Likert scale showed greater global improvement in the L-arginine group (48%, 10 of 21) compared to the placebo group (24%, 6 of 25) at 3 months (p = 0.05) with a decrease in pain intensity (p = 0.04), and tendency toward improvement in urgency (p = 0.06) and frequency of pain (p = 0.09). Using an intention to treat approach to analysis there were no differences between groups. Oral L-arginine (1,500 mg. daily) may decrease pain and urgency in a subset of interstitial cystitis patients.

Effects of l-arginine treatment on symptoms and bladder nitric oxide levels in patients with interstitial cystitis

Objectives. Nitric oxide (NO) is involved in host defense reactions, and NO production is elevated in various inflammatory disorders. We have found very high levels of luminal NO in the urinary bladder of patients with interstitial cystitis. Oral treatment with low doses of l-arginine, the substrate for NO production, has been reported to alleviate symptoms in patients with interstitial cystitis. The aim of our investigation was to evaluate the effect of higher doses of l-arginine in patients with interstitial cystitis and to study the effects of l-arginine on NO production in the bladder. Methods. Nine women (age 69 ± 3 years) with interstitial cystitis were treated daily with 3 or 10 g of l-arginine for 5 weeks. Symptoms were evaluated with an interstitial cystitis symptom score index, and NO production was measured. Patients with stress incontinence (n = 18) were used as control subjects for measurement of NO levels. Results. NO concentration in the urinary bladder was markedly elevated in the patients with interstitial cystitis (239 ± 60 ppb) compared with the control patients (15 ± 2 ppb). NO levels did not change in the patients with interstitial cystitis after oral treatment with l-arginine (189 ± 72 ppb). There was no significant change in the symptom scores at either dose after 5 weeks of l-arginine treatment. Conclusions. l-arginine treatment in the doses used in this study did not change NO production in the urinary bladder in patients with interstitial cystitis. Furthermore, the patients in our study did not notice any relief of their symptoms.

Clinical Response to an Oral Prostaglandin Analogue in Patients with Interstitial Cystitis

Objective: To assess the efficacy of the oral prostaglandin analogue misoprostol in controlling the symptoms of interstitial cystitis in patients with refractory disease. Methods: Twenty-five patients were commenced on misoprostol 600 µg daily for 3 months. Patients who responded to therapy were offered treatment for a further 6 months. Assessment of the response was by a voiding log and an interstitial cystitis symptom score. Results: At 3 months, 14 patients (56%) had significantly improved, and after a further 6 months, 12 patients (48%) had a sustained response. The incidence of adverse drug effects was 64%. Most side effects were minimal, and the response rate in patients who were able to tolerate the drug was 87% at 3 months and 75% at 9 months. Conclusions: The oral prostaglandin analogue misoprostol is effective in treating the symptoms of interstitial cystitis. It is possible that prostaglandins have a cytoprotective action in the urinary bladder.

Improvement in Interstitial Cystitis Symptom Scores During Treatment With Oral L-Arginine

Purpose Urinary nitric oxide synthase activity is decreased in patients with interstitial cystitis. Since nitric oxide may be an important determinant of the symptoms and immunological responses associated with interstitial cystitis, patients with this disease were treated with oral L-arginine, the substrate for nitric oxide synthase. Materials and Methods Ten patients took 1.5 gm. L-arginine orally daily for 6 months. Interstitial cystitis symptoms were surveyed before and during the 6-month trial. Results Oral L-arginine treatment resulted in a significant decrease in urinary voiding discomfort, lower abdominal pain and vaginal/urethral pain. Urinary frequency during the day and night also significantly decreased. Conclusions This self-controlled study provides evidence that long-term oral L-arginine improves interstitial cystitis related symptoms.