A Phase 2 interventional study of BOTOX 100U in normal saline and Normal saline in Interstitial Cystitis, sponsored by Buddhist Tzu Chi General Hospital. Status unknown at 1 site in Taiwan. Open to participants aged 20 Years and older. Per ClinicalTrials.gov, last updated 2022-03-25.
Sponsored by Buddhist Tzu Chi General Hospital · Phase 2, Interventional, and Treatment
Low energy shock wave (LESW) is known to facilitate tissue regeneration with analgesic and anti-inflammatory effects. LESW treatment has been demonstrated effective in treatment of nonbacterial prostatitis and chronic pelvic pain syndrome. LESW reduced pain behavior and down-regulated the NGF expression, suppressed bladder overactivity by decreasing inflammation, IL-6 and COX2 expression and NGF expression. Previous rat interstitial cystitis (IC) models have shown LESW could increase urothelial permeability, facilitate intravesical botulinum toxin A (BoNT-A) delivery and block acetic acid induced hyperactive bladder, suggesting LESW might be a potential therapeutic candidate for relieving bladder inflammatory conditions and overactivity. A double-blind, randomized, placebo-controlled physician-initiated study revealed LESW treatment was associated with a statistically significant decrease in O'Leary-Saint Symptom Score and visual analog scale of pain in patients with interstitial cystitis/bladder pain syndrome (IC/BPS), but the improvement was not superior to the sham LESW treatment. Previous studies found the urothelial dysfunction and deficits of cell differentiation are fundamental pathophysiology of IC/BPS. Through intravesical platelet-rich plasma injections, the chronic inflammation in IC/BPS bladders could be reduced and improved cell differentiation of urothelium. Botox injection or liposome encapsulated Botox could also inhibit inflammation and improve IC/BPS symptoms. However, the Botox injection needs anesthesia and certain complications might occur. There is no study to test if LESW plus Botox intravesical instillation could improve bladder inflammation and relieve IC/BPS symptoms. This study aims to investigate the therapeutic efficacy and safety of concomitant LESW plus intravesical BoNT-A instillation for IC/BPS refractory to conventional treatments.
Interstitial cystitis/ bladder pain syndrome (IC/BPS) is a bladder disorder with unknown etiology and difficult treatment. Novel treatments have been searched to adequately improved symptoms. Low energy shock wave (LESW) increased urothelial permeability, facilitated intravesical botulinum toxin A (BoNT-A) delivery and blocked acetic acid induced hyperactive bladder. Rats that received BoNT-A plus LESW showed a significantly reduced response (48.6% decreased intercontractile interval) to acetic acid instillation without compromising voiding function. Rats pre-treated with BoNT-A plus LESW showed a decreased inflammatory reaction (p \<0.05), and decreased expressions of SNAP-23 (p \< 0.05), SNAP-25 (p = 0.061) and COX-2 (p \< 0.05) compared with the control group. These results support LESW as a promising method to deliver BoNT-A across urothelium without the need for injection. LESW is known to facilitate tissue regeneration with analgesic and anti-inflammatory effects. LESW treatment reduced pain behavior and down-regulated the NGF expression (33.3%, P \< 0.05) on day 4 and IL-6 (40.9%, P \< 0.05). LESW treatment suppressed bladder overactivity (intercontractile interval 77.8% increase, P \< 0.05) by decreasing inflammation and COX2 (38.6%, P \< 0.05) expression and NGF expression (25.2%, P = 0.0812). Previous study revealed that LESW might be a potential candidate for relieving bladder inflammatory conditions and overactivity. Recent clinical trial also revealed that Intravesical instillation of BoNT-A and LESW is a safe and effective method for the treatment of refractory overactive bladder with a durable response for 2 months. A double-blind, randomized, placebo-controlled physician-initiated study enrolled 54 patients with IC/BPS. The patients were assigned to LESW or placebo. At 4 weeks post-treatment, both groups were associated with a statistically significant decrease in OSS and VAS pain scale. A significantly higher proportion of patients on LESW responded as improved in the VAS ≥ 3 vs placebo (P = 0.035). At 12 weeks post-treatment, improvement in the VAS ≥ 3 was 57.1% vs 19.0% (LESW vs placebo; P = 0.011). No significant adverse events were found in either group. This study aims to investigate the therapeutic efficacy and safety of concomitant LESW plus intravesical BoNT-A instillation for IC/BPS patients refractory to conventional treatments.
Materials and Methods
Eligible participants of either gender with IC/BPS refractory to at least two treatments will be enrolled to this study. Participants are randomly allocated to receive either treatment in 1:1 ratio according to the permuted block randomization code as the following:
(A) LESW treatment with 3000 shocks, and followed by intravesical instillation of 30ml normal saline. (placebo group)
(B) LESW with 3000 shocks, and followed by intravesical BoNT-A 100U instillation. (treatment group)
Urine samples will be collected for urinary protein and biomarkers analysis.
227 studies on the registry are indexed under Cystitis, Interstitial; 32 are open to participants now.
This study's planned enrollment of 75 is above the median of 50 across 152 interventional studies indexed under Cystitis, Interstitial.
Browse Cystitis, Interstitial studies →Buddhist Tzu Chi General Hospital is the lead sponsor of 88 studies on the registry; 20 are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
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Exclusion Criteria:
BOTOX 100U in normal saline (BoNT-A/NS) 30ml in single intravesical instillation
Drug: BOTOX 100U in normal saline
Normal saline (N/S) 30ml in single intravesical instillation
Drug: Normal saline
LESW with 3000 shocks, frequency of 3 pulses per second, and maximum total energy flow density 0.25 mJ/mm2 , and followed by intravesical BoNT-A 100U instillation in 30ml normal saline retained in the bladder for 2 hours, every one week for 4 times.
Also known as: BOTOX
LESW treatment with 3000 shocks, frequency of 3 pulses per second, and maximum total energy flow density 0.25 mJ/mm2 , and followed by intravesical instillation of 30ml normal saline retained in the bladder for 2 hours after LESW application, every one week for 4 times.
Also known as: Saline
O'Leary-Sant Symptom Score
Change of the O'Leary-Sant symptom score (including Interstitial Cystitis Symptom Index from 0 to 10 points and Interstitial Cystitis Problem Index, from 0 to 20 points; a higher score indicates a worse symptom severity)
Time frame: from baseline to 3 month after the treatment day
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Local or systemic adverse events such as hematuria, miction pain, difficult urination, or any systemic symptoms such as fever, general weakness, dyspnea, etc.)
Time frame: from baseline to 3 month after the treatment day
Global response assessment (GRA)
Global response assessment (GRA) of satisfaction by the patient (categorized into -3, -2, -1, 0, 1, 2, 3 units of scale, indicating markedly worse to markedly improved) at 1 month after the treatment day. An improvement of GRA by 2 units of scale at 1 month is considered effective.
Time frame: 1 month after the treatment day
Visual analog score (VAS) for pain
Net change of the Visual analog score (VAS) for pain (from 0 to 10 units of scale, indicating no pain (0) to severe pain (10))
Time frame: from baseline to 1 month and 3 months after the first treatment day
Functional bladder capacity
Net change of functional bladder capacity (FBC, in milliliter)
Time frame: from baseline to 1 month and 3 months after the first treatment day
Voiding frequency per day
Net change of voiding frequency at daytime and voiding frequency at night time as record in 3-day voiding diary
Time frame: from baseline to 1 month and 3 months after the first treatment day
maximum flow rate
Net changes of the maximum flow rate (Qmax, in milliliter/second)
Time frame: from baseline to 1 month after the first treatment day
voided volume
Net changes of the voided volume (in milliliter)
Time frame: from baseline to 1 month after the first treatment day
Pos-tvoid residual volume (PVR)
Net changes of the PVR (in milliliter)
Time frame: from baseline to 1 month after the first treatment day
urinary nerve growth factor (NGF)
Changes of urinary NGF level in urine (in nanogram/milliliter)
Time frame: from baseline to 1 month and 3 months after the first treatment day
urinary brain derived neurotrophic factor (BDNF)
Changes of urinary BDNF (in nanogram/milliliter)
Time frame: from baseline to 1 month and 3 months after the first treatment day
Inflammatory cytokine IL-2 level
Changes of cytokine IL-2 level (in nanogram/milliliter)
Time frame: from baseline to 1 month and 3 months after the first treatment day
Inflammatory cytokines IL-6 level
Changes of cytokines IL-6 level (in nanogram/milliliter)
Time frame: from baseline to 1 month and 3 months after the first treatment day
Inflammatory cytokine IL-8 level
Changes of cytokine IL-8 level (in nanogram/milliliter)
Time frame: from baseline to 1 month and 3 months after the first treatment day
Inflammatory cytokine IL-1 beta level
Changes of cytokine IL-1 beta level (in nanogram/milliliter)
Time frame: from baseline to 1 month and 3 months after the first treatment day
Safety outcome (Local and systemic adverse events)
Any adverse events occurring after treatment, including hematuria, micturition pain, difficulty in urination, urinary tract infection, or systemic symptoms
Time frame: from baseline to 1 month and 3 months after the first treatment day
Plan to share: No
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Started May 2021 (actual). Primary completion is estimated for Jul 2024, 38 months after the start.
Of 18 phase 2 interventional studies under Cystitis, Interstitial, half reached primary completion within 27 months of starting (the median), counting those still running; a quarter within 21 and three quarters within 38. This study's planned 38 months is above that.
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This study is status unknown, as verified in Mar 2022. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Botulinum toxin type A
Buddhist Tzu Chi General Hospital