A Randomized, Placebo-controlled Trial of Nitrous Oxide During In-office Bladder Botox Injections

A Randomized, Placebo Controlled Trial of Nitrous Oxide/Oxygen Plus Standard Care Versus Standard Care Alone During In-office Intradetrusor onabotulinumtoxinA (Botox) Injections

The goal of this clinical trial is to assess if a mix of nitrous oxide and oxygen can improve pain control during bladder Botox injections. The primary question it aims to answer is: Does using nitrous oxide lower the overall level of pain during the procedure?

Researchers will compare a 50:50 nitrous oxide/oxygen mixture (administered with the Pro-Nox system) plus standard care (with lidocaine in the bladder) to sham mask plus standard care to see if nitrous oxide works better for lowering pain.

Participants will:

• Receive their bladder Botox injection in the office setting
• Either use nitrous oxide/oxygen plus standard care during the procedure, or sham mask plus standard care
• Answer brief questions about pain, anxiety, satisfaction, and willingness to repeat the procedure

Study Overview

• Status: Not yet recruiting
• Conditions: Pain; Overactive Bladder; Urinary Bladder, Overactive; Urinary Incontinence; Pelvic Floor Disorders; Urinary Bladder, Neurogenic; Urge Incontinence; Urinary Incontinence, Urge; Neurogenic Bladder; Urinary Bladder Neurogenesis
• Intervention / Treatment: Drug: Standard Care for Bladder Botox Injection; Other: Sham Mask; Drug: Pro-Nox Nitrous Oxide/Oxygen Delivery System

Detailed Description

This study will assess if a 50:50 nitrous oxide and oxygen mixture can lower pain in women undergoing in-office bladder onabotulinumtoxinA (Botox) injections. Many people report pain during this procedure, and pain is a common reason not to repeat the procedure. Nitrous oxide is a fast-acting inhaled analgesic that is used commonly in the office setting.

This randomized controlled trial will compare nitrous oxide/oxygen plus standard care with sham mask plus standard care. Participants assigned to the nitrous oxide group will receive nitrous oxide via the Pro-Nox device during the procedure. Both, participants assigned to the nitrous oxide group and the standard care alone group, will receive the usual lidocaine instilled in the bladder for at least 15 minutes.

The study will measure participants overall pain during the procedure. It will also assess peak pain, overall anxiety, satisfaction, willingness to repeat, interest in using nitrous oxide in future bladder Botox procedures, and side effects. Nitrous oxide is expected to wear off within minutes, allowing participants to leave the clinic without restrictions.

This research study would be first randomized-controlled trial to evaluate nitrous oxide for pain management during this common in-office procedure.

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Colton H Mabis, MD; Phone Number: 5134634300; Email: colton_mabis@trihealth.com

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • Cincinnati Urogynecology Associates
    • Cincinnati, Ohio, United States, 45220
      • Trihealth (Good Samaritan Hospital, Bethesda North Hospital)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult women ≥18 years old scheduled for in-office intradetrusor botulinum toxin injection and able to consent.

Exclusion Criteria:

• Known/suspected vitamin B12 or folate deficiency or high-risk state (e.g., pernicious anemia, malabsorption, post-bariatric or strict vegan without supplementation)
• currently pregnant
• severe/unstable pulmonary disease or baseline hypoxemia requiring supplemental home oxygen
• eye or ear surgery in the last six weeks
• trapped-air conditions (e.g., untreated pneumothorax, bowel obstruction)
• severe active otitis/sinus disease
• inability to follow directions
• history of adverse reaction to nitrous oxide

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sham Mask Plus Standard Care; The sham mask plus standard care group will receive a mask that is connected to the Pro-Nox system but with the valves turned completely off; therefore they will inhale room air plus standard care: intravesical instillation of 1-2% lidocaine solution (30-50 mL) with at least 15 minutes dwell time before the procedure.	Drug: Standard Care for Bladder Botox Injection; Standard care includes intravesical instilled 1-2% lidocaine with a dwell time of at least 15 minutes before the procedure.; Other Names: Lidocaine; Standard care; Local analgesia; Intravesical lidocaine; Standard analgesia; Other: Sham Mask; The Sham Mask will involve that participant using the same mask as that of the Nitrous Oxide group, but connected to a Pro-Nox system that is turned completely off. They will therefore receive room air through the mask.; Other Names: Placebo; Room Air
Experimental: Nitrous Oxide Plus Standard Care; Participants in this group will receive standard care plus 50:50 mix of inhaled nitrous oxide/oxygen self-administered using the Pro-Nox system during the bladder Botox procedure.	Drug: Standard Care for Bladder Botox Injection; Standard care includes intravesical instilled 1-2% lidocaine with a dwell time of at least 15 minutes before the procedure.; Other Names: Lidocaine; Standard care; Local analgesia; Intravesical lidocaine; Standard analgesia; Drug: Pro-Nox Nitrous Oxide/Oxygen Delivery System; The Pro-Nox system delivers a fixed 50:50 mixture of nitrous oxide and oxygen for patient self-administered inhaled analgesia. Participants will self-administer nitrous oxide throughout the in-office bladder Botox procedure.; Other Names: Nitrous; Nitrous oxide; Pro-Nox; Nitrous oxide/oxygen 50:50 mixture; Nitrous oxide/oxygen; Nitrous oxide analgesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Pain (10-point NRS)	Patient self-reported overall pain during the procedure on an 11-point numeric rating scale.	At least 3 minutes after completion of the procedure.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Pain (10-point NRS)	Patient self-reported peak pain during the procedure on an 11-point numeric rating scale.	At least 3 minutes after completion of the procedure.
Peak Pain Timing	Patient self-reported timing of peak pain during the procedure, as it corresponds to different steps during the procedure.	At least 3 minutes after completion of the procedure.
Overall Anxiety (10-point NRS)	Patient self-reported overall anxiety during the procedure on an 11-point numeric rating scale.	At least 3 minutes after completion of the procedure.
Satisfaction with Pain Management (10-point NRS)	Patient self-reported satisfaction with pain management during the procedure on an 11-point numeric rating scale.	At least 3 minutes after completion of the procedure.
Willingness to Repeat (5-point Likert)	Patient self-reported willingness to repeat under similar pain and anxiety management conditions, on a 5-point Likert scale.	At least 3 minutes after completion of the procedure.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nitrous Interest (5-point Likert)	Patient self-reported interest in use of nitrous oxide for pain and anxiety management in a future procedure, on a 5-point Likert scale.	At least 3 minutes after completion of the procedure.
Adverse Effects	Physician reported adverse events encountered peri-operatively.	Immediately following the procedure. Completed by performing surgeon.
Blinding Assessment	Patient self-reported perceived treatment assignment (nitrous oxide/oxygen vs sham mask), recorded as nitrous oxide, sham mask, or unsure.	At least 3 minutes after completion of the procedure.

Collaborators and Investigators

• Sponsor: TriHealth Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 28, 2026
• First Submitted That Met QC Criteria: January 28, 2026
• First Posted (Actual): February 4, 2026

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Analgesia; Overactive Bladder; OnabotulinumtoxinA; Nitrous Oxide; Urinary Incontinence; Botox; Pain Management; Urogynecology; Botulinum Toxins, Type A; Pelvic Floor Disorder; Urge Incontinence; Bladder Botox; Intradetrusor Injection; Office-based Procedures
• Additional Relevant MeSH Terms: Urogenital Diseases; Neurologic Manifestations; Nervous System Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Urination Disorders; Lower Urinary Tract Symptoms; Urological Manifestations; Neurobehavioral Manifestations; Urinary Bladder Diseases; Perceptual Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain; Urinary Incontinence; Urinary Bladder, Overactive; Agnosia; Urinary Bladder, Neurogenic; Pelvic Floor Disorders; Urinary Incontinence, Urge; Health Services Administration; Health Care Quality, Access, and Evaluation; Organic Chemicals; Quality of Health Care; Quality Indicators, Health Care; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Inorganic Chemicals; Nitrogen Compounds; Elements; Oxides; Oxygen Compounds; Chalcogens; Gases; Nitrogen Oxides; Lidocaine; Nitrous Oxide; Standard of Care; Oxygen
• Other Study ID Numbers: 23-130

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Do not plan to share individual participant data with other researchers.

Drug and device information, study documents

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