VNX001 for Painful Bladder Syndrome
Recruiting in Palo Alto (17 mi)
+4 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Vaneltix Pharma, Inc.
Must not be taking: Antidepressants, Anticonvulsants, St. John's Wort
Disqualifiers: Pregnancy, Neurogenic bladder, CNS disorders, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This is an open-label study that will enroll participants with Interstitial Cystitis / Bladder Pain Syndrome (IC/BPS).
The study will assess PRN (as needed) dosing of up to 6 intravesical (via catheter) doses of VNX001 (study drug) to treat acute instances of moderate to severe bladder pain over a 14-day period. The main aim of the study is to tally the number of doses and assess pain before and after doses. The study will review the safety and tolerability of VNX001.
Participants will need to attend up to seven (7) clinic visits (1 for screening and up to 6 visits for VNX001 dosing) or at least one (1) clinic visit (for a combined screening/dosing visit) and 5 telephone visits over the course of 14 days. Participants will also be asked complete a diary or telephone call each day of the study, in order to record bladder pain, urinary urgency, side effects, and medications taken.
Do I need to stop taking my current medications for the trial?
The trial does not specify if you need to stop all current medications, but certain medications are prohibited. You cannot take phenytoin, carbamazepine, St. John's Wort, phenobarbital, or rifampin. If you are on a tricyclic antidepressant or a GABA analogue like gabapentin or pregabalin, you must be on a stable dose for at least 3 weeks.
Is VNX001 safe for humans?
Vanilloid receptor agonists like capsaicin and resiniferatoxin, which may be similar to VNX001, have been studied for bladder conditions. While they show some promise, larger studies are needed to confirm their safety and effectiveness, as current data is not strong enough to recommend routine use.
12345How does the drug VNX001 differ from other treatments for Painful Bladder Syndrome?
VNX001 is unique because it targets the TRPV1 receptor, which is involved in bladder pain and hypersensitivity. This approach is different from other treatments as it aims to desensitize the nerve fibers responsible for pain, potentially offering relief by reducing the bladder's overactive response to stimuli.
26789Eligibility Criteria
This trial is for individuals who have completed Study VNX001-111 and suffer from Interstitial Cystitis / Bladder Pain Syndrome (IC/BPS). It's designed to help those with moderate to severe bladder pain by testing a new treatment called VNX001.Inclusion Criteria
I completed Study VNX001-111 and meet all other requirements.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1 day
1 visit (in-person)
Treatment
Participants receive up to 6 intravesical doses of VNX001 over 14 days to treat acute bladder pain
14 days
Up to 6 visits (in-person) or 1 combined visit (in-person) and 5 telephone visits
Follow-up
Participants are monitored for safety and effectiveness after treatment
3 days
1 follow-up call
Participant Groups
The study tests the safety and effectiveness of up to six doses of VNX001, administered directly into the bladder over two weeks. Participants will track their pain levels before and after each dose, as well as any side effects.
1Treatment groups
Experimental Treatment
Group I: Open Label ArmExperimental Treatment1 Intervention
VNX001 intravesical administration PRN up to 6 doses over 14 days. The VNX001 effective dose is 15 mL of buffered lidocaine HCl (200 mg) and sodium heparin (50,000 USPU).
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Arizona Urology SpecialistsTucson, AZ
Valley Urology, Inc.Fresno, CA
Prestige Medical GroupTustin, CA
Georgia UrologyCartersville, GA
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
Vaneltix Pharma, Inc.Lead Sponsor
Prevail Infoworks, IncCollaborator
References
Use of vanilloids in urologic disorders. [2019]The bladder is an organ rich in vanilloid targets: dense unmyelinated c-fibers partially responsible for bladder sensation and response to noxious stimuli. Drugs such as capsaicin and resiniferatoxin (RTX) interact with the VR1 vanilloid receptor subtype to initially excite then subsequently desensitize the c-fibers. This chapter examines the literature describing the use of vanilloid receptor agonists in the treatment of the following urological disorders: neurogenic bladder (NGB), overactive bladder (OAB), and interstitial cystitis/painful bladder syndrome (IC/PBS). Review of the literature was performed using Pubmed and the following key words "capsaicin," "resiniferatoxin (RTX)," and "neurogenic bladder," "overactive bladder (OAB)," and "interstitial cystitis," "painful bladder syndrome." Articles focusing on randomized trials comparing intravesical administration of a vanilloid receptor agonist to placebo and those in English were reviewed. We conclude that capsaicin and RTX do appear to provide some acceptable treatment results in patients with neurogenic bladder, though larger studies are needed to confirm this. Although efficacy has been shown in some studies, currently the use of vanilloids cannot be recommended for routine use in patients with OAB as the need for catheterization may cause the risk to outweigh the benefit of treatment. Similarly, for the treatment of BPS, vanilloid receptor agonists lack strong evidence for efficacy or tolerability; larger studies are needed to define their role. Understanding how vanilloids are able to impact these disorders, however, may help further elucidate their underlying pathophysiological processes.
The molecular basis of urgency: regional difference of vanilloid receptor expression in the human urinary bladder. [2007]Treatments targeting vanilloid receptor TRPV1 are effective in some bladder disorders. Our aim was to determine the expression profiles of TRPV1 in regions of human bladder and test the hypothesis that there would be an upregulation of TRPV1 in mucosa of patients with bladder hypersensitivity but not idiopathic detrusor overactivity (IDO).
A Systematic Review of Therapeutic Approaches Used in Experimental Models of Interstitial Cystitis/Bladder Pain Syndrome. [2021]Interstitial cystitis/bladder pain syndrome (IC/BPS) is a multifactorial, chronic bladder disorder with limited therapeutic options currently available. The present review provides an extensive overview of therapeutic approaches used in in vitro, ex vivo, and in vivo experimental models of IC/BPS. Publications were identified by electronic search of three online databases. Data were extracted for study design, type of treatment, main findings, and outcome, as well as for methodological quality and the reporting of measures to avoid bias. A total of 100 full-text articles were included. The majority of identified articles evaluated therapeutic agents currently recommended to treat IC/BPS by the American Urological Association guidelines (21%) and therapeutic agents currently approved to treat other diseases (11%). More recently published articles assessed therapeutic approaches using stem cells (11%) and plant-derived agents (10%), while novel potential drug targets identified were proteinase-activated (6%) and purinergic (4%) receptors, transient receptor potential channels (3%), microRNAs (2%), and activation of the cannabinoid system (7%). Our results show that the reported methodological quality of animal studies could be substantially improved, and measures to avoid bias should be more consistently reported in order to increase the value of preclinical research in IC/BPS for potential translation to a clinical setting.
Efficacy and safety of intravesical instillation of KRP-116D (50% dimethyl sulfoxide solution) for interstitial cystitis/bladder pain syndrome in Japanese patients: A multicenter, randomized, double-blind, placebo-controlled, clinical study. [2021]To evaluate the efficacy and safety of intravesical KRP-116D, 50% dimethyl sulfoxide solution compared with placebo, in interstitial cystitis/bladder pain syndrome patients.
Intravesical capsaicin versus resiniferatoxin for the treatment of detrusor hyperreflexia in spinal cord injured patients: a double-blind, randomized, controlled study. [2013]Chemical defunctionalization of C-fiber bladder afferents with intravesical vanilloids such as capsaicin (CAP) or resiniferatoxin (RTX) improves detrusor hyperreflexia in humans and animals. The little existing data comparing the efficacy and tolerance of these 2 vanilloid agents seem to favor RTX in 10% alcohol over CAP, which is usually diluted in 30% alcohol. We compared the efficacy and tolerability of the 2 vanilloid agonists in what to our knowledge is the first randomized, controlled study comparing nonalcohol CAP vs RTX in 10% alcohol in neurogenic patients with detrusor hyperreflexia.
Vanilloid receptor and detrusor instability. [2019]Very recently, a membrane receptor (vanilloid receptor type 1 [VR-1]) sensitive to capsaicin or resiniferatoxin (RTX) was identified in small- and medium-sized dorsal root ganglion neurons that give rise to most unmyelinated sensory fibers. After vanilloid binding to VR-1, these neurons remain transiently desensitized; that is, less reactive to natural stimuli. It is this effect of vanilloid substances that is being investigated for its potential therapeutic utility. In the urinary bladder, VR-1-expressing fibers are extremely abundant in the mucosa and in the muscular layer. In the latter, VR-1 fibers are intimately apposed to smooth muscle cells. The demonstration, several years ago, that these fibers were involved in detrusor hyperreflexia of spinal origin and in bladder pain processing, justified the clinical application of intravesical capsaicin or RTX in humans with these bladder diseases. More recently, the experimental and clinical evidence that the same type of bladder sensory fibers were also involved in detrusor instability made a strong case for intravesical RTX assay in patients with idiopathic detrusor instability.
Bladder pain induced by prolonged peripheral alpha 1A adrenoceptor stimulation involves the enhancement of transient receptor potential vanilloid 1 activity and an increase of urothelial adenosine triphosphate release. [2018]Pathophysiological mechanisms of chronic visceral pain (CVP) are unknown. This study explores the association between the sympathetic system and bladder nociceptors activity by testing the effect of a prolonged adrenergic stimulation on transient receptor potential vanilloid 1 (TRPV1) activity and on urothelial adenosine triphosphate (ATP) release.
Effects of early intravesical administration of resiniferatoxin to spinal cord-injured rats in neurogenic detrusor overactivity. [2020]To investigate if intravesical administration during spinal shock of resiniferatoxin (RTX), an ultrapotent desensitizing agonist of transient receptor potential vanilloid-1 (TRPV1), would silence TRPV1-expressing bladder afferents at an early stage of disease progression and modulate neurogenic detrusor overactivity (NDO) emergence.
Lack of TRPV1 inhibits cystitis-induced increased mechanical sensitivity in mice. [2021]Transient receptor potential vanilloid 1 (TRPV1) is highly expressed in primary afferent neurons. Tissue damage generates an array of chemical mediators that activate and sensitize afferent nerve fibers, and sensitization of afferent nerve fibers plays an important role in development of visceral pain. We investigated participation of TRPV1 in visceral pain associated with bladder inflammation induced in mice by systemic treatment with cyclophosphamide or intravesical instillation of acrolein. The effects of experimental cystitis on bladder function (an indicator of visceral pain) and the threshold of response to mechanical or thermal stimuli of the hind paws were investigated using TRPV1 knock-out (KO) and congenic wild-type (WT) mice. We found that cystitis induced bladder mechanical hyperreactivity and increased mechanical sensitivity of hind paws in WT, but not in TRPV1 KO mice. Lack of functional TRPV1 did not inhibit development of histological evidence of bladder inflammation, or increased expression of mRNAs for nerve growth factor, endothelial nitric oxide synthase, cyclooxygenase-2 and bradykinin receptors in urothelium. Cystitis did not affect the threshold of response to thermal stimuli in WT or KO mice. These results suggest that TRPV1 is essential for cystitis-induced bladder mechanical hyperreactivity. Also, TRPV1 participates in development of visceral pain, as reflected by referred increased mechanosensitivity in peripheral tissues in the presence of visceral inflammation.