Nitrous Oxide for the Treatment of Complex Regional Pain Syndrome

NCT03879538 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 19-150
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Complex Regional Pain Syndrome

Outcome Measures

Primary Outcomes (1)

• Pain Score

  scales ranging from 0 - "no pain" to 10 - "worst pain ever" based on the PROMIS-29 v2.0 questionnaire.

  one-week and one-month follow-up time points

Secondary Outcomes (2)

• PROMIS-29 Survey Physical Health Z-score, Mental Health Z-score

  one-week and one-month follow-ups after treatments were ended

• PGIC Scale

  one-week and one-month follow-ups.

Study Arms (2)

The nitrous oxide group

ACTIVE COMPARATOR

Nitrous oxide group will receive 50% nitrous oxide mixed with 50% oxygen, inhalation therapy for a duration of 2 hours via an FDA-approved mask breathing circuit.

Drug: Nitrous Oxide

The Control Group

PLACEBO COMPARATOR

Control group will receive 50% oxygen, inhalation therapy for a duration of 2 hours via an FDA-approved mask breathing circuit.

Drug: Oxygen

Interventions

Nitrous Oxide DRUG

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.

Also known as: 50 % Nitrous Oxide plus 50% Oxygen

The nitrous oxide group

Oxygen DRUG

A total of three inhalation treatments with 50% oxygen (6 total exposure hours) over one week with 2 or 3 days between each session.

Also known as: 50% Oxygen

The Control Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be diagnosed with CRPS based on the revised International Association for the Study of Pain criteria.
• Duration of disease must be at least 6 months.
• Written informed consent.

You may not qualify if:

• Patients who had no subjective benefit from ketamine infusions, as determined by interview during the recruitment process.
• Patients taking more than 60mg of morphine equivalents or more daily for an alternative chronic pain condition.
• 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.
• Patients with congestive heart failure of any etiology that are NYHA Class III or IV
• Patients with moderate or severe pulmonary hypertension as determined by echocardiogram or right heart catheterization.
• Patients with intraocular surgery within the past 14 days
• Patients with worker's compensation claims and active litigation.
• Patients who have been diagnosed with COPD.
• Patients who use home oxygen therapy for any condition.
• Diagnosis of Alcohol Use Disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).
• Illicit drug use within the past three months (not including marijuana).
• Pregnant patients or patients with upcoming planned pregnancy.

Sponsors & Collaborators

• The Cleveland Clinic: lead

Study Sites (1)

Cleveland Clinic Pain Management

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Complex Regional Pain Syndromes

Interventions

Nitrous Oxide; Oxygen

Condition Hierarchy (Ancestors)

Autonomic Nervous System Diseases; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Oxides; Gases; Inorganic Chemicals; Nitrogen Compounds; Oxides; Oxygen Compounds; Chalcogens; Elements

Limitations and Caveats

limitations include the purely subjective nature of pain which was our primary outcome. Validity of the trial thus depends critically on adequacy of blinding. Because many patients can detect inhaled nitrous oxide, we gave all participants midazolam which has similar effects. But it remains possible that some patients could distinguish nitrous oxide from air, and were thus biased.

Results Point of Contact

• Title: Alparslan Turan
• Organization: Cleveland Clinic

turana@ccf.org

2162172312

Study Officials

• Jason Hale, MD

  Anesthesiologist

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Patients and other involved providers will be blinded to the treatment type. Research investigators administering the treatments will not be blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 31, 2019
• First Posted: March 18, 2019
• Study Start: July 2, 2019
• Primary Completion: July 28, 2022
• Study Completion: July 28, 2022
• Last Updated: February 9, 2024
• Results First Posted: February 9, 2024

Record last verified: 2024-02

Locations

US (1)