Efficacy and Safety of Low Energy Shock Wave Plus BotulinumToxin A in Treating Patients With Interstitial Cystitis

NCT05275647 | Unknown Phase 2 DMC

• 1 other identifier: IRB 110-078-A
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Interstitial Cystitis

Keywords

Low energy shock wave; interstitial cystitis; botulinum toxin A; urothelium

Outcome Measures

Primary Outcomes (2)

• 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)

  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.)

  from baseline to 3 month after the treatment day

Secondary Outcomes (14)

• Global response assessment (GRA)

  1 month after the treatment day

• Visual analog score (VAS) for pain

  from baseline to 1 month and 3 months after the first treatment day

• Functional bladder capacity

  from baseline to 1 month and 3 months after the first treatment day

• Voiding frequency per day

  from baseline to 1 month and 3 months after the first treatment day

• maximum flow rate

  from baseline to 1 month after the first treatment day

Study Arms (2)

Treatment group : BoNT-A 100 U in Normal saline

EXPERIMENTAL

BOTOX 100U in normal saline (BoNT-A/NS) 30ml in single intravesical instillation

Drug: BOTOX 100U in normal saline

Placebo group : Normal saline

PLACEBO COMPARATOR

Normal saline (N/S) 30ml in single intravesical instillation

Drug: Normal saline

Interventions

BOTOX 100U in normal saline DRUG

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

Treatment group : BoNT-A 100 U in Normal saline

Normal saline DRUG

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

Placebo group : Normal saline

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults with age of 20 years old or above
• Patients with symptoms of frequency, urgency, and bladder pain at full bladder for more than 6 months.
• Proven to have glomerulations (at least grade 1) by cystoscopic hydrodistention under anesthesia in recent 1 year
• Free of active urinary tract infection
• Free of bladder outlet obstruction on enrolment
• Free of overt neurogenic bladder dysfunction and limitation of ambulation.
• Patient or his/her legally acceptable representative agrees to sign the written informed consent form

You may not qualify if:

• Patient's lower urinary tract symptoms can be effectively treated by conventional therapy
• Patient or his/her legally acceptable representative cannot sign the written informed consent form
• Patient cannot complete the consecutive 3- day voiding diary on the visiting day
• Patient had been treated for overactive bladder by enterocystoplasty
• Patients with severe cardiopulmonary disease and such as congestive heart failure, arrhythmia, poorly controlled hypertension, not able to receive regular follow-up
• Patient has bladder outlet obstruction on enrollment
• Patients has post-void residual \>250ml
• Patients with uncontrolled confirmed diagnosis of acute urinary tract infection
• Patients have laboratory abnormalities at screening including: ALT\> 3 x upper limit of normal range, AST\> 3 x upper limit of normal range; Patients have abnormal serum creatinine level \> 2 x upper limit of normal range
• Patient has coagulation disorder
• Female patients who is pregnant, lactating, or with child-bearing potential without contraception.
• Patients with any other serious disease considered by the investigator not in the condition to enter the trial
• Patient had received intravesical hyaluronic acid insillation treatment for IC within recent 6 months before enrolment
• Patient had received intravesical onabotulinumtoxinA treatment for IC within recent 12 months before enrolment
• Patients participated investigational drug trial within 1 month before entering this study

Sponsors & Collaborators

• Buddhist Tzu Chi General Hospital: lead
• Ministry of Science and Technology, Taiwan: collaborator
• Hualien Tzu Chi General Hospital: collaborator

Study Sites (1)

Buddhist Tzu Chi General Hospital

Hualien City, 970, Taiwan

RECRUITING

MeSH Terms

Conditions

Cystitis, Interstitial

Interventions

Botulinum Toxins, Type A; Saline Solution; Sodium Chloride

Condition Hierarchy (Ancestors)

Cystitis; Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Hann-Chorng Kuo, M.D.

  Department of Urology, Buddhist TzuChi General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hann-Chorng Kuo, M.D.

CONTACT

886-3-8561825; hck@tzuchi.com.tw

Shu-Hui Liu

CONTACT

886-3-8561825; hck@tzuchi.com.tw

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants and investigator are blinded to the treatment arm.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chairman, Department of Urology

Model Details: This is a double-blind, randomized, placebo-controlled physician initiated study enrolled patients with refractory IC/BPS.

Study Record Dates

• First Submitted: January 13, 2022
• First Posted: March 11, 2022
• Study Start: May 18, 2021
• Primary Completion: July 1, 2024
• Study Completion: September 1, 2024
• Last Updated: March 25, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)