Nerve Stimulation Therapy for Bladder Pain Syndrome

Overseen By Eli Medvescek, MD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Walter Reed National Military Medical Center

Disqualifiers: Neurostimulation, Malignancy, Coagulation, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 1 day

38 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Many women suffer from bladder pain syndrome (BPS). There are many treatments, but there is no one universally effective option. The goal of this clinical trial is to explore the use of electrical energy directed towards a group of nerves, called the superior hypogastric plexus, for treatment of BPS in women over the age of 18 with a diagnosis of BPS. The main question it aims to answer is: does use of electrical micro-current directed at the superior hypogastric plexus improve pain associated with BPS over the use of placebo? There is data from many different studies that suggest that this kind of therapy might provide relief of BPS symptoms. Participants will be asked to participate for a total of six months from the date of their first nerve treatment. At the first appointment, they will be evaluated in the Walter Reed Chronic Pain clinic and asked several questions about the severity and personal management of their symptoms. The procedure will then be performed by inserting two needles into the back (one on either side of the spine) and directing extremely short bursts of electrical micro-current towards the target nerve. The medical term for this is "pulsed radiofrequency ablation." This procedure causes disruption on a microscopic level of nerve fibers that send pain sensations to the bladder and other organs in the pelvis. Some participants will receive treatment, whereas others will receive sham (placebo). Participants will not be informed of their treatment group until the conclusion of the study. Following this initial appointment, participants will be asked about their symptoms at 1-, 3-, and 6-month follow-up appointments. Participants will be asked about pain, mood symptoms, sexual function, and measures of bladder irritation. The procedure will only be performed once. At the study conclusion, researchers will compare treatment and sham groups to see if pain scores, as well as other secondary outcomes listed above, are different between these groups. Benefits of this study may include possible relief of BPS symptoms. This may help to advance research about treatments for BPS. This is a novel approach to the treatment of BPS and as such may provide benefits greater than those found in treatment outside of the study.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have an implantable neurostimulation device, you cannot participate in the trial.

Is nerve stimulation therapy using pulsed radiofrequency safe for humans?

Pulsed radiofrequency (PRF) has been safely used to manage various types of pain, including joint and neuropathic pain, by using low energy bursts to modulate nerve activity without causing significant damage. ^{1 2 3 4 5}

How is pulsed radiofrequency ablation treatment different from other treatments for bladder pain syndrome?

Pulsed radiofrequency ablation (PRF) is unique because it uses low energy, short bursts of radiofrequency to modulate nerve activity, which can help manage pain without destroying tissue. This approach is different from other treatments for bladder pain syndrome, as it focuses on altering nerve signals rather than using medications or invasive procedures. ^{1 2 5 6 7}

What data supports the effectiveness of the treatment Pulsed Radiofrequency Ablation for Bladder Pain Syndrome?

Research on similar treatments, like percutaneous tibial nerve stimulation, shows that nerve stimulation can help manage symptoms of bladder pain syndrome by reducing pain and improving bladder function. Additionally, neuromodulation, which involves stimulating nerves to alter pain signals, is recommended for patients who do not respond to other treatments. ^{7 8 9 10 11}

Who Is on the Research Team?

Eli Medvescek, MD

Principal Investigator

Walter Reed National Military Medical Center

Are You a Good Fit for This Trial?

This trial is for women over 18 with bladder pain syndrome (BPS), who are eligible for DEERS health care benefits and have a specific score on a BPS diagnostic test. It's not suitable for those who don't meet these criteria.

Inclusion Criteria

DEERS-eligible health care beneficiaries

I am female.

I have been diagnosed with Bladder Pain Syndrome.

Exclusion Criteria

I have a neurogenic bladder or a spinal cord injury.

I have an infection where I get my shots.

Current pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo pulsed radiofrequency ablation or sham procedure targeting the superior hypogastric plexus

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up appointments at 1, 3, and 6 months

6 months

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Pulsed radiofrequency ablation
• Sham ablation

Trial Overview The study tests pulsed radiofrequency ablation—a procedure using electrical micro-currents aimed at nerves to relieve BPS symptoms—against sham ablation, which is like a placebo. Participants will be compared after one treatment over six months.

How Is the Trial Designed?

Group I: Pulsed Radiofrequency Ablation Arm Experimental Treatment 1 Intervention

18 total subjects in this arm. Subjects will be laid in the prone position. Local anesthesia will be administered. The appropriate spinal interspace will be identified under fluoroscopic guidance and hollow-tip needles will be inserted through the back into the retroperitoneal space adjacent to the superior hypogastric plexus. A microelectrode will be inserted through the hollow needle. A test pulse will be delivered. When proper positioning has been confirmed, 4mL of 1% lidocaine without epinephrine will be administered to reduce discomfort associated with radiofrequency ablation. Pulsed radiofrequency ablation will be performed at a pulse frequency of 2Hz, pulse width of 20ms, temperature of 42 degrees Celsius, total duration 120 seconds. The microelectrode and hollow-tip needle will then be withdrawn.

Group II: Sham Arm Placebo Group 1 Intervention

18 total subjects in this arm. Subjects will be laid in the prone position. Local anesthesia will be administered. The appropriate spinal interspace will be identified under fluoroscopic guidance and hollow-tip needles will be inserted through the back into the retroperitoneal space adjacent to the superior hypogastric plexus. A microelectrode will be inserted through the hollow needle. A test pulse will be delivered. Sham pulsed radiofrequency ablation will then be performed with the radiofrequency generator disconnected from the microelectrode. The duration of the sham procedure will be 120 seconds. The microelectrode and hollow-tip needle will then be withdrawn.

Pulsed radiofrequency ablation is already approved in United States, European Union for the following indications:

Approved in United States as Pulsed Radiofrequency Ablation for:

• Bladder Pain Syndrome (BPS)
• Chronic Pelvic Pain

Approved in European Union as Pulsed Radiofrequency Ablation for:

• Bladder Pain Syndrome (BPS)
• Chronic Pelvic Pain

Who Is Running the Clinical Trial?

Walter Reed National Military Medical Center

Lead Sponsor

Trials

149

Recruited

33,800+

Published Research Related to This Trial

In a pilot study of 21 subjects with interstitial cystitis/bladder pain syndrome (IC/BPS), 70% experienced some degree of symptom improvement after treatment with percutaneous tibial nerve stimulation (PTNS), although only 30% met the criteria for 'moderately' or 'markedly improved' on the Global Response Assessment after 12 weeks.

The study reported no adverse events associated with PTNS, suggesting it is a safe treatment option for managing IC/BPS symptoms, despite the challenges in recruitment and follow-up that limited the statistical significance of the findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous tibial nerve stimulation for the treatment of interstitial cystitis/bladder pain syndrome: a pilot study. Sudol, NT., Guaderrama, N., Adams-Piper, E., et al.[2021]

Both intravesical injections of platelet-rich plasma (PRP) and Botulinum toxin A (BoNT-A) showed similar efficacy in improving symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS) in a study of 56 female patients, with significant improvements noted in IC symptom scores for both treatments.

However, BoNT-A was associated with a higher risk of urinary tract infections (15.4% vs. 0% for PRP) and dysuria, suggesting that while both treatments are effective, PRP may be a safer option with fewer adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the Clinical Efficacy and Adverse Events between Intravesical Injections of Platelet-Rich Plasma and Botulinum Toxin A for the Treatment of Interstitial Cystitis Refractory to Conventional Treatment. Jhang, JF., Yu, WR., Kuo, HC.[2023]

Pulsed electromagnetic field (PEMF) therapy is a non-invasive treatment that has shown significant efficacy in reducing pain for various chronic pain conditions, suggesting it may also benefit patients with interstitial cystitis/bladder pain syndrome (IC/BPS).

Randomized, double-blinded, placebo-controlled trials have demonstrated positive safety and efficacy profiles for PEMF in treating conditions like low back pain and fibromyalgia, indicating its potential as a therapeutic option for managing chronic pain and fatigue in IC/BPS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulsed electromagnetic field (PEMF) as an adjunct therapy for pain management in interstitial cystitis/bladder pain syndrome. Ross, C., Overholt, T., Xu, R., et al.[2022]

Neuromodulation is recommended as a fourth-line treatment for bladder pain syndrome/interstitial cystitis (BPS/IC) patients who have not responded to other treatments, and it has shown effectiveness in managing chronic pelvic pain disorders.

Sacral neuromodulation is particularly effective for patients with BPS without Hunner's lesions, with benefits that can last over the mid- to long-term, while posterior tibial nerve stimulation and pudendal nerve stimulation can also be beneficial in specific contexts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current role of neuromodulation in bladder pain syndrome/interstitial cystitis. Padilla-Fernández, B., Hernández-Hernández, D., Castro-Díaz, DM.[2022]

In a clinical trial involving 53 patients with overactive bladder who did not respond to traditional therapies, percutaneous peripheral afferent nerve stimulation was found to be a safe and effective treatment, with 71% of patients classified as treatment successes after 12 weeks.

Patients experienced significant reductions in daytime (25%) and nighttime (21%) voiding frequencies, as well as a 35% reduction in urge incontinence, with no significant adverse events reported, highlighting its potential as a minimally invasive option for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous afferent neuromodulation for the refractory overactive bladder: results of a multicenter study. Govier, FE., Litwiller, S., Nitti, V., et al.[2017]

Pulsed radiofrequency (PRF) applied to the dorsal root ganglion (DRG) shows potential for treating neuropathic pain, but the evidence is primarily based on small studies with low quality, as only 5 out of 28 studies were randomized controlled trials (RCTs).

With a total of 991 participants across all studies, the overall quality of evidence is very low, indicating that the current findings on PRF's efficacy and safety are preliminary and need to be validated through larger, high-quality RCTs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Pulsed Radiofrequency as a Method of Dorsal Root Ganglia Stimulation in Patients with Neuropathic Pain: A Systematic Review. Vuka, I., Marciuš, T., Došenović, S., et al.[2021]

Pulsed radiofrequency (PRF) treatment effectively modulates various biological pathways involved in chronic neuropathic pain, impacting nociceptive signaling, immune activity, and synaptic function, as identified in a review of 20 publications.

PRF treatment influences key components such as ion channels, neurotransmitters, and inflammatory cytokines, suggesting a complex mechanism of action that may help in pain management, although definitive causal relationships to clinical outcomes remain unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulsed Radiofrequency in Interventional Pain Management: Cellular and Molecular Mechanisms of Action - An Update and Review. Sam, J., Catapano, M., Sahni, S., et al.[2021]

In a study of 116 patients treated with pulsed radiofrequency (PRF) for supraorbital neuralgia (SN) over a maximum follow-up of 127 months, 78.4% achieved initial pain control after just one treatment, indicating high efficacy.

The median pain-free duration was 52 months, with cumulative pain-free survival rates of 70% at 6 months and 37% at 10 years, while no severe complications were reported, suggesting that PRF is a safe long-term treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Outcomes of Pulsed Radiofrequency for Supraorbital Neuralgia: A Retrospective Multicentric Study. Xiao, X., Chai, G., Liu, L., et al.[2022]

Pulsed radiofrequency (PRF) treatment shows promising efficacy for cervical radicular pain, particularly when applied to the dorsal root ganglion, based on evidence from four randomized controlled trials.

However, PRF was found to be less effective than conventional radiofrequency techniques for lumbar facet pain, and more research is needed to evaluate its effectiveness for other spinal conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comprehensive review of pulsed radiofrequency in the treatment of pain associated with different spinal conditions. Facchini, G., Spinnato, P., Guglielmi, G., et al.[2022]

Pulsed radiofrequency (PRF) stimulation has been found to be an effective treatment for managing pain in various joint disorders, including cervical and lumbar facet, sacroiliac, knee, and glenohumeral joint pain, based on a review of 34 studies.

While the results are promising, the review highlights the need for more high-quality studies to further confirm the efficacy of PRF in treating joint pain, ensuring that clinicians can make well-informed treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effectiveness of Pulsed Radiofrequency on Joint Pain: A Narrative Review. Boudier-Revéret, M., Thu, AC., Hsiao, MY., et al.[2020]

Pulsed radiofrequency (PRF) treatment effectively alleviated neuropathic pain in two patients with cubital tunnel syndrome, with one patient experiencing complete pain relief and the other showing significant improvement over a 6-month follow-up period.

No adverse effects were reported in either patient, suggesting that PRF is a safe intervention for managing neuropathic pain associated with peripheral nerve pathologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of neuropathic pain induced by cubital tunnel syndrome using pulsed radiofrequency: Two case reports. Kwak, S., Jeong, D., Choo, YJ., et al.[2022]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Percutaneous tibial nerve stimulation for the treatment of interstitial cystitis/bladder pain syndrome: a pilot study. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of the Clinical Efficacy and Adverse Events between Intravesical Injections of Platelet-Rich Plasma and Botulinum Toxin A for the Treatment of Interstitial Cystitis Refractory to Conventional Treatment. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Pulsed electromagnetic field (PEMF) as an adjunct therapy for pain management in interstitial cystitis/bladder pain syndrome. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Current role of neuromodulation in bladder pain syndrome/interstitial cystitis. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Percutaneous afferent neuromodulation for the refractory overactive bladder: results of a multicenter study. [2017]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Pulsed Radiofrequency as a Method of Dorsal Root Ganglia Stimulation in Patients with Neuropathic Pain: A Systematic Review. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Pulsed Radiofrequency in Interventional Pain Management: Cellular and Molecular Mechanisms of Action - An Update and Review. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Long-term Outcomes of Pulsed Radiofrequency for Supraorbital Neuralgia: A Retrospective Multicentric Study. [2022]

9. England pubmed.ncbi.nlm.nih.gov

A comprehensive review of pulsed radiofrequency in the treatment of pain associated with different spinal conditions. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

The Effectiveness of Pulsed Radiofrequency on Joint Pain: A Narrative Review. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Management of neuropathic pain induced by cubital tunnel syndrome using pulsed radiofrequency: Two case reports. [2022]