Detrusor Nerve Radiofrequency Ablation for Overactive Bladder in Women

Overactive bladder (OAB) is a common condition that significantly impacts the quality of life in women, especially those with urge urinary incontinence (UUI) or mixed incontinence with a predominant urgency component. Current treatments for OAB, including behavioral therapy and pharmacologic agents, often have limited long-term efficacy, tolerability issues, or low adherence rates. There is a significant need for alternative, non-invasive therapies that can provide symptom relief with fewer side effects. The MORPHEUSV system is a vaginally delivered radiofrequency (RF) energy device designed to remodel submucosal tissue through controlled thermal stimulation. This technology is currently being investigated for its ability to improve bladder control by targeting pelvic tissue support and neuromodulation pathways. The device is investigational for this indication and is being studied under an FDA-approved Investigational Device Exemption (IDE G250071). This is a prospective, randomized, multicenter, double-blind, sham-controlled clinical trial designed to evaluate the safety and efficacy of the MORPHEUSV RF device in women aged 22 to 80 with idiopathic OAB and at least 7 episodes of UUI per week. The study will enroll approximately 202 participants at up to 12 sites across the United States. Participants will be randomized 2:1 to either a single session of active RF treatment or a sham (placebo) treatment. The primary outcome is the proportion of participants achieving a ≥50% reduction in UUI episodes from baseline at 6 months. Secondary and exploratory outcomes include symptom reduction across urgency, frequency, nocturia, and quality of life metrics, as well as device-related adverse events. Blinding will be maintained through the use of an identical sham applicator with no RF energy delivery. A crossover option is available for sham subjects who complete the 6-month follow-up, allowing them to receive the active treatment. All participants will be followed for 12 months after their initial intervention to evaluate durability of response and long-term safety. An internal data review committee will periodically evaluate cumulative safety data. The study is conducted under Good Clinical Practice (GCP) guidelines and will be overseen by Sterling IRB.

• Detrusor nerve radiofrequency ablation (Device): A single, vaginal radiofrequency (RF) treatment. The procedure is performed with a bipolar RF applicator and requires no anesthesia. Delivered in a single session in an outpatient setting.
• Simulated (sham) detrusor nerve radiofrequency ablation (Device): A simulated (sham) radiofrequency (RF) treatment, but with no energy delivered. The procedure mimics the appearance, duration, and positioning of the active device, without therapeutic effect.

Primary outcomes

• Proportion of participants achieving ≥50% reduction in weekly urge urinary incontinence (UUI) episodes [6 months post-treatment]: The percentage of participants who achieve at least a 50% reduction from baseline in the number of UUI episodes per week, as recorded in a 7-day bladder diary. This is the primary efficacy endpoint used to evaluate the effectiveness of the MORPHEUSV device compared to sham.

Secondary outcomes

• Change from baseline in mean number of UUI episodes per week [6 months]: Mean change in UUI episodes per week from baseline, based on 7-day bladder diary.
• Change from baseline in mean number of urgency episodes per week [6 months]: Mean change in urgency episodes per week from baseline, based on bladder diary.
• Change from baseline in mean number of micturitions per 24 hours [6 Months]: Change in average number of daily voids as measured via bladder diary.
• Change from baseline in Incontinence Quality of Life (I-QOL) total score [6 Months]: Mean change from baseline in total score on the Incontinence Quality of Life Questionnaire (I-QOL), a validated 22-item patient-reported outcome measure assessing the impact of urinary incontinence on quality of life. Total scores range from 0 to 100, with higher scores indicating better quality of life.
• Change from baseline in Urgency Perception Scale (UPS) score [6 Months]: Mean change from baseline in urgency perception severity measured using the Urgency Perception Scale (UPS), a validated patient-reported scale assessing urinary urgency severity. UPS scores range from 0 to 3, with higher scores indicating greater urgency severity (worse symptoms).
• Incidence and severity of adverse events [12 Months]: Frequency and severity of treatment-emergent adverse events in each arm, collected at all follow-up visits.

Sex: Female, ages: 22 Years to 80 Years

INCLUSION CRITERIA:

* Female, aged 22 to 80 years inclusive at the time of consent.
* History of idiopathic overactive bladder (OAB) symptoms for ≥6 months.
* At least 7 episodes of urge urinary incontinence (UUI) over 3 days, as recorded in a 3-day bladder diary during screening.
* Urge-predominant incontinence, defined as greater number of UUI episodes than stress urinary incontinence (SUI) episodes during screening.
* Willing and able to complete the 3-day bladder diary.
* Willing to discontinue OAB medications (e.g., anticholinergics, beta-3 agonists) at least 2 weeks prior to baseline treatment visit, if currently taking such medications.
* Willing to use a reliable method of contraception during the study period, if of childbearing potential and sexually active.
* Negative pregnancy test at screening (if applicable).
* Willing and able to provide written informed consent and comply with study procedures and follow-up schedule.

EXCLUSION CRITERIA:

* Predominant stress urinary incontinence (SUI) based on bladder diary
* Currently pregnant, breastfeeding, or planning pregnancy during the study
* History of neurologic conditions affecting bladder function (e.g., multiple sclerosis, spinal cord injury, Parkinson's disease)
* Active urinary tract infection (UTI) at screening
* History of interstitial cystitis, bladder pain syndrome, or chronic pelvic pain
* Prior or current bladder cancer, pelvic malignancy, or pelvic radiation
* Pelvic organ prolapse beyond the hymen (POP-Q stage > II)
* Implanted neuromodulation device or prior sacral nerve stimulation
* Use of bulking agents, Botox, or surgical treatment for incontinence within 12 months
* Prior pelvic floor RF treatment or laser vaginal rejuvenation
* Significant pelvic anatomical abnormalities that interfere with treatment
* Use of investigational drug or device within 30 days before screening
* Any condition that, in the investigator's opinion, would interfere with safe study participation or data integrity
* Uncontrolled systemic disease (e.g., uncontrolled diabetes, cardiovascular disease)
* Inability or unwillingness to comply with study requirements or follow-up

• Mickey Karram, MD, Study director, Foundation for Female Health Awareness