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
Intervention: Nitrous Oxide; Oxygen
Intervention description: 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.
Intervention MeSH terms: Nitrous Oxide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
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)
Masking description: Patients and other involved providers will be blinded to the treatment type. Research investigators administering the treatments will not be blinded.
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients must be diagnosed with CRPS based on the revised International Association
             for the Study of Pain criteria.

          2. Duration of disease must be at least 6 months.

          3. Written informed consent.

        Exclusion Criteria:

          1. Patients who had no subjective benefit from ketamine infusions, as determined by
             interview during the recruitment process.

          2. Patients taking more than 60mg of morphine equivalents or more daily for an
             alternative chronic pain condition.

          3. Patients with both coronary artery disease (as determined by cardiac catheterization)
             and a functional status of less than 4 metabolic equivalents. The limited functional
             status must be secondary to cardiopulmonary symptoms (angina, dyspnea on exertion).
             Patients with coronary artery disease and a limited functional status (<4 METS)
             secondary to chronic pain can be included.

          4. Patients with congestive heart failure of any etiology that are NYHA Class III or IV

          5. Patients with moderate or severe pulmonary hypertension as determined by
             echocardiogram or right heart catheterization.

          6. Patients with intraocular surgery within the past 14 days

          7. Patients with worker's compensation claims and active litigation.

          8. Patients who have been diagnosed with COPD.

          9. Patients who use home oxygen therapy for any condition.

         10. Diagnosis of Alcohol Use Disorder as defined by the Diagnostic and Statistical Manual
             of Mental Disorders (DSM-5).

         11. Illicit drug use within the past three months (not including marijuana).

         12. Pregnant patients or patients with upcoming planned pregnancy.