A Novel Medical System for Quantitative Diagnosis and Personalized Precision Botulinum Neurotoxin Injection in Chronic Pelvic Pain Management

An Novel Medical System for Quantitative Diagnosis and Personalized Precision Botulinum Neurotoxin Injection in Chronic Pelvic Pain Management

The purpose of this study is to evaluate if it is possible to use intravaginal high-density surface electromyography to guide Botulinum neurotoxin (BoNT) injection to treat pelvic floor muscle overactivity that complicates Chronic Pelvic Pain (CPP).

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Pain; Pelvic Floor Disorders; Interstitial Cystitis; Pelvic Floor; Relaxation
• Intervention / Treatment: Drug: Botulinum Neurotoxin; Device: High Density Surface Electromyographic, precision botulinum neurotoxin injection guidance medical device

Detailed Description

The management of pelvic floor overactivity (PFOA) using focal BoNT injection has been gaining clinical interest. Evidence has shown that BoNT injections to the levator ani in patients with CPP generated a greater than 50% improvement in symptoms at least 72% of the time, suggesting a promising efficacy of BoNT therapy. The current clinical standard for BoNT injection employs a fixed injection template or the manual palpation of a contracted muscle, followed by an injection towards the palpating finger. As such, the injection is highly subjective, operator-dependent, variable, and not tailored to individual patients, which may lead to inconsistent outcomes. Trigger point targeted injections have been practiced for many years worldwide, yet a recent randomized controlled trial reported no significant difference in outcome between trigger point targeted BoNT injections versus a saline placebo. Furthermore, it has also been reported that neuromuscular junction (NMJ) and trigger points are distributed in well-defined separate areas with a distance of approximately 10 mm apart. It has also been shown that BoNT injections made 10 mm away from the NMJ can reduce the efficacy of BoNT by 46%. Therefore, injections targeted at the trigger point may, in turn, compromise therapeutic efficacy.

The rationale of this study is that BoNT acts at the NMJ, where the neuromuscular junctions are densely located. By specifying the muscle(s) responsible for the pelvic floor overactivity, and the offending NMJ using high density surface electromyography (HD-sEMG), BoNT can be injected with greater accuracy and objectivity to optimize treatment efficacy. The investigators aim to test the hypothesis that interstitial cystitis patients in the guided injection arm will demonstrate lower hypertonic metrics and improved quality of life. The purpose of this study is to provide preliminary evidence supporting the use of HD-sEMG and NMJ mapping to guide BoNT efficacy.

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Nicholas C Dias, PhD; Phone Number: 2816581953; Email: nickdias@hillmedgroup.com

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
      • Contact: Christopher P Smith, MD, MBA, MSS; Phone Number: 713-798-4001; Email: cps@bcm.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Inclusion criteria for interstitial cystitis/bladder pain syndrome (IC/BPS) patients will be:

  1. Woman aged 18 to 60.
  2. Have a clinical diagnosis of IC/BPS.
  3. Pain, pressure, or discomfort in the bladder and/or pelvic area for the past 6 months or more, associated with lower urinary tract symptoms (such as frequency of urination), in the absence of other explanation of the symptoms (e.g., urinary tract infection).
  4. Myofascial pain diagnosed with palpable contracted muscle fibers.
  5. Pelvic muscle tenderness by assessment of pelvic floor muscles on digital pelvic examination.
  6. Pelvic floor hypertonicity (PFH), measured using vaginal manometry (pressure > 35 cm∙H2O).
  7. Ability to provide informed consent.

Exclusion Criteria:

• Exclusion criteria consist of the following:

  1. History of pelvic malignancy and sexually transmitted diseases.
  2. Bleeding disorder such as coagulopathy
  3. History of neurological disorders, such as spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis or myasthenia gravis.
  4. Pregnancy, breast feeding or desiring for pregnancy in the coming year.
  5. Subjects with history of pelvic surgery (e.g., pain from mid-urethral sling or pelvic mesh),
  6. Pelvic malignancy (urinary tract, gynecologic, gastrointestinal)
  7. Active fistula
  8. Radiation cystitis
  9. Cyclophosphamide cystitis
  10. Pre-existing anorectal disorders
  11. Infections near the injection sites
  12. History of drug or alcohol abuse
  13. Hypersensitivity to BoNT
  14. Steroids or hormone usage will be carefully considered by the research team for inclusion.

Participants with on-going BoNT therapies will not be screened until the complete drug washout is confirmed.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Template Injection; For the standard template injection, 200 units of BoNT diluted in 6mL of preservative saline will be prepared. 1/4 of the prepared BoNT solution will be administered to each of the pubococcygeus and puborectalis muscle at 5 and 7 o'clock position, respectively. The index finger will be used for palpation as the 20-gauge spinal needle with a trumpet guide (i.e. paracervical block kit) piercing through the vaginal mucosa to the intended muscle groups. The syringe will be withdrawn before each injection to avoid intravascular injection.	Drug: Botulinum Neurotoxin; Botulinum neurotoxin will be injected into the pelvic floor muscles following either a standard template (standard injection arm), or guided using high-density surface EMG (guided arm).
Experimental: Guided Injection; For the guided injection, pelvic floor injections (total of 4) will be made to the pubococcygeus and puborectalis muscles each, at NMJ locations (1.5 ml per site), at patient-specific locations and depths identified from vaginal HD-sEMG recordings. NMJ mappings will be generated for each participant. The channel locations will provide angle measurements for each NMJ. The device will calculate these parameters based on acquired HD-sEMG. The index finger will be used for palpation and guidance of injection needle through the vaginal mucosa to the defined injection sites. The BoNT dosage with respect to the total 200 units administered to each site will be patient specific, determined as the ratio of the resting average resting root-mean square (RMS) value of a specific region divided by the total average resting RMS.	Drug: Botulinum Neurotoxin; Botulinum neurotoxin will be injected into the pelvic floor muscles following either a standard template (standard injection arm), or guided using high-density surface EMG (guided arm).; Device: High Density Surface Electromyographic, precision botulinum neurotoxin injection guidance medical device; A personalized, precision botulinum neurotoxin injection guidance medical device, utilizing an intra-vaginal high-density surface EMG system to optimize the treatment outcomes in chronic pelvic pain (CPP) management.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypertonic metrics of the pelvic muscles defined by intra-vaginal surface EMG	The pelvic floor hypertonicity will be assessed by evaluating the amplitudes of intra-vaginal high-density surface electromyography recordings.	Baseline
Hypertonic metrics of the pelvic muscles defined by intra-vaginal surface EMG	The pelvic floor hypertonicity will be assessed by evaluating the amplitudes of intra-vaginal high-density surface electromyography recordings.	1-Month Post Injection
Hypertonic metrics of the pelvic muscles defined by intra-vaginal surface EMG	The pelvic floor hypertonicity will be assessed by evaluating the amplitudes of intra-vaginal high-density surface electromyography recordings.	3-Months Post Injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global response assessment	Compared to prior to the treatment, is the patient very much better, much better, a little better, no change, a little worse, much worse, or very much worse.	1-Month Post Injection
Global response assessment	Compared to prior to the treatment, is the patient very much better, much better, a little better, no change, a little worse, much worse, or very much worse.	3-Months Post Injection

Collaborators and Investigators

• Sponsor: HillMed Inc.
• Collaborators: Baylor College of Medicine; University of Houston

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: September 16, 2021
• First Submitted That Met QC Criteria: September 21, 2021
• First Posted (Actual): September 30, 2021

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: electromyography; chronic pelvic pain; hypertonicity
• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Pain; Neurologic Manifestations; Pregnancy Complications; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Cystitis; Chronic Pain; Pelvic Floor Disorders; Cystitis, Interstitial; Pelvic Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Botulinum Toxins
• Other Study ID Numbers: R44HD107822 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No