Nitrous Oxide for the Treatment of Complex Regional Pain Syndrome
Condition: Complex Regional Pain Syndrome
MeSH terms: Complex Regional Pain Syndromes; Reflex Sympathetic Dystrophy; Syndrome; Somatoform Disorders
Study type: Interventional
Phase: Phase 3

Summary: 
      Patients will then be randomized via a web-based randomization system Redcap Allocation will
      be stratified based on the presence of a pre-existing spinal cord stimulator to either the
      nitrous oxide study group or the oxygen control group.

      The nitrous oxide group will receive 50% nitrous oxide mixed with 50% oxygen, and the control
      group will receive 50% oxygen (oxygen plus air mixture). Both groups will undergo inhalation
      therapy for a duration of 2 hours via an FDA-approved mask breathing circuit. Vital signs
      (blood pressure, respiratory rate, heart rate) will be monitored every 30 minutes. Pulse
      oximetry monitoring will be continuous. Patients will be monitored for side effects including
      nausea, vomiting, desaturation, sedation, respiratory depression, and dizziness. Patients and
      other involved providers will be blinded to the treatment type.
    

Detailed description: 
      Daily opioid consumption data will be collected by having patients record and report their
      daily opioid use before and after treatment. Oral and transdermal opioids will be converted
      to standardized morphine equivalents and adjusted for bioavailability.

      Patients will present for the first scheduled treatment and they will fill out the PROMIS-29
      v2 survey and the SF-MPQ-2 (6 neuropathic pain items). Patients will also turn in their
      opioid use log.

      Vital signs will be obtained. Patients with significantly abnormal vital signs or vital signs
      that are significantly deviated from baseline will be referred to appropriate medical care.

      Patients will then be randomized via a web-based randomization system Redcap. Group
      allocation will be stratified based on the presence of a pre-existing spinal cord stimulator
      to either the nitrous oxide study group or the oxygen control group.

      The nitrous oxide group will receive 50% nitrous oxide mixed with 50% oxygen, and the control
      group will receive 50% oxygen. Both groups will undergo inhalation therapy for a duration of
      2 hours via an FDA-approved mask breathing circuit. Active Control, because patients may be
      able to tell if they are receiving nitrous oxide, patient blinding may be compromised.
      Therefore, we plan to utilize an active control. Both groups will receive 2 mg of intravenous
      midazolam, to infuse over 5 minutes, at the start of each breathing treatment session. IVs
      will be removed at the conclusion of each breathing treatment. Vital signs (blood pressure,
      respiratory rate, heart rate) will be monitored every 30 minutes. Pulse oximetry monitoring
      will be continuous. Patients will be monitored for side effects including nausea, vomiting,
      desaturation, sedation, respiratory depression, and dizziness. Patients and other involved
      providers will be blinded to the treatment type. Research investigators administering the
      treatments will not be blinded.

      At the conclusion of inhalation therapy, the gas will be turned off and patients will breathe
      room air. All patients will be monitored for an additional 30 minutes. This recovery time is
      more than sufficient to ensure nitrous oxide is completely eliminated in those patients who
      receive it. Patients will be monitored and asked about side effects.

      Patients will receive a total of three treatments (6 total exposure hours) over one week with
      2 or 3 days between each session. Possible treatment schedules: Monday-Wednesday-Friday,
      Wednesday-Friday-Monday, or Friday-Monday-Wednesday. After the conclusion of the third
      treatment, patients will be followed with phone calls as detailed in the Measurement section
      below.

      1. Drug Handling Instructions

      a. Nitrous oxide for the study will be stored at room temperature in appropriately labeled
      E-cylinder tanks.
    

Intervention name(s): Nitrous Oxide; Oxygen
Intervention type(s): Drug; Drug
Intervention description(s): A total of three inhalation treatments with 50% Nitrous Oxide plus 50% oxygen (6 total exposure hours) over one week with 2 or 3 days between each session.; A total of three inhalation treatments with 50% oxygen (6 total exposure hours) over one week with 2 or 3 days between each session.
Other intervention name(s): 50 % Nitrous Oxide plus 50% Oxygen; 50% Oxygen
Intervention MeSH terms: Nitrous Oxide
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The nitrous oxide group will receive 50% nitrous oxide mixed with 50% oxygen, and the control group will receive 50% oxygen (oxygen plus air mixture). Both groups will undergo inhalation therapy for a duration of 2 hours via an FDA-approved mask breathing circuit. Vital signs (blood pressure, respiratory rate, heart rate) will be monitored every 30 minutes.
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment