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Nitrous Oxide for the Treatment of Complex Regional Pain Syndrome

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ClinicalTrials.gov Identifier: NCT03879538
Recruitment Status : Enrolling by invitation
First Posted : March 18, 2019
Last Update Posted : July 19, 2019
Sponsor:
Information provided by (Responsible Party):
The Cleveland Clinic

Brief Summary:

Patients will then be randomized via a web-based randomization system Redcap without stratification 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.


Condition or disease Intervention/treatment Phase
Complex Regional Pain Syndrome Drug: Nitrous Oxide Drug: Oxygen Phase 3

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 without stratification 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
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.
Primary Purpose: Treatment
Official Title: A Prospective Randomized Controlled Pilot Study Nitrous Oxide for the Treatment of Complex Regional Pain Syndrome
Actual Study Start Date : July 2, 2019
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021


Arm Intervention/treatment
Active Comparator: The nitrous oxide group
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
a total of three treatments (6 total exposure hours) over one week with 2 or 3 days between each session.

Placebo Comparator: The Control Group
Control group will receive 50% oxygen, inhalation therapy for a duration of 2 hours via an FDA-approved mask breathing circuit.
Drug: Oxygen
a total of three treatments (6 total exposure hours) over one week with 2 or 3 days between each session.




Primary Outcome Measures :
  1. The change of pain in patients with Complex Regional Pain Syndrome (CRPS) [ Time Frame: 7 days and then at 30 days ]
    44 patients, which is 100% of the study subjects, will receive 6 treatments of nitrous oxide exposure to assess the outcome in reducing pain in CRPS by completing the PROMIS‐29 v2 survey questionnaire using 0(no pain to 10 (worse pain) scale.

  2. The change of pain in patients with Complex Regional Pain Syndrome (CRPS) [ Time Frame: 7 days and then at 30 days ]
    44 patients, which is 100% of the study subjects, will receive 6 treatments of nitrous oxide exposure to assess the outcome in reducing pain in CRPS by completing the SF-MPQ-2 which is a short form McGill pain questionnaire (6 neuropathic pain items) each items ranging from 0 (no pain) to 10 (worse pain).

  3. The change of pain in patients with Complex Regional Pain Syndrome (CRPS) [ Time Frame: 7 days and then at 30 days ]
    44 patients, which is 100% of the study subjects, will receive 6 treatments of nitrous oxide exposure to assess the outcome in reducing pain in CRPS by completing a the Patient's global impression of change survey measured with PGIC which is a seven point scale ranging from 1 -("very much improved" to 7-("very much worse")survey scores.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03879538


Locations
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United States, Ohio
Cleveland Clinic Pain Management
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
The Cleveland Clinic

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Responsible Party: The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT03879538     History of Changes
Other Study ID Numbers: 19-150
First Posted: March 18, 2019    Key Record Dates
Last Update Posted: July 19, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Syndrome
Somatoform Disorders
Complex Regional Pain Syndromes
Reflex Sympathetic Dystrophy
Disease
Pathologic Processes
Mental Disorders
Autonomic Nervous System Diseases
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nitrous Oxide
Anesthetics, Inhalation
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents