Nitrous Oxide as Treatment for Fibromyalgia

NCT05357066 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IRB20-1169
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to explore a potential role of nitrous oxide in treating pain associated with fibromyalgia.

Conditions

Fibromyalgia; Central Neuropathic Pain

Keywords

Fibromyalgia; Pain

Outcome Measures

Primary Outcomes (1)

• Monitor changes in NPRS score

  Monitoring changes in 'Numeric Pain Rating Scale' (NPRS) diagnostic score to determine effectiveness a 60-minute session of inhaled 50% nitrous oxide vs placebo has on symptoms associated with fibromyalgia. The NPRS is a validated self-report diagnostic asking patients to indicate the intensity of current, best, and worst pain levels over the past 24 hours on a scale of 0 (no pain) to 10 (worst pain imaginable). Response and remission will be based on a 30% improvement in average daily mean (max and min) NPRS score.

  Over 8-weeks from baseline (length of study participation)

Secondary Outcomes (4)

• Changes in FIQR

  Over 8-weeks from baseline (length of study participation)

• Changes in Global Impression of Change Scale

  Over 8-weeks from baseline (length of study participation)

• Computerize Adaptive Testing - Mental Health (CAT-MH) measurements

  Over 8-weeks from baseline

• Hospital Anxiety and Depression Scale

  Over 8-weeks from baseline (length of study participation)

Other Outcomes (1)

• Adverse events

  Over 8-weeks (length of study participation)

Study Arms (2)

Treatment; Nitrous Oxide 50%

ACTIVE COMPARATOR

A single 60-minute session of inhaled 50% nitrous oxide.

Drug: Nitrous oxide gas for inhalation

Control; Oxygen-air mixture

PLACEBO COMPARATOR

A single 60-minute session of inhaled Oxygen-air mixture

Drug: Placebo

Interventions

Placebo DRUG

Administration of the placebo (oxygen-air mixture \[FiO2 ≈0.3\]), will be under the direct supervision of a licensed practitioner who is experienced in the use and administration of the study drug, and is familiar with the indications, effects, dosages, methods, and frequency and duration of administration, and with the hazards, contraindications, and side effects and the precautions to be taken (MD, or CRNA); with study patient monitoring of pulse oximetry, heart rate, respiratory, non-invasive blood pressure, and end-tidal carbon dioxide.

Also known as: Sham

Control; Oxygen-air mixture

Nitrous oxide gas for inhalation DRUG

Administration of inhaled 50% nitrous oxide in oxygen (FiO2 0.5) will be under the direct supervision of a licensed practitioner who is experienced in the use and administration of the study drug, and is familiar with the indications, effects, dosages, methods, and frequency and duration of administration, and with the hazards, contraindications, and side effects and the precautions to be taken (MD, or CRNA); with study patient monitoring of pulse oximetry, heart rate, respiratory, non-invasive blood pressure, and end-tidal carbon dioxide.

Also known as: Nitrous Oxide, Nitrous, N2O, Laughing gas

Treatment; Nitrous Oxide 50%

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• American College of Rheumatology Revised criteria for fibromyalgia (2016-ACR)
• Subjects 18 -75 years of age.
• Self-reported pain of at least 4 on the Numeric Pain Rating Scale (NPRS) at screening and baseline.
• Subject receives and agrees to remain on their stable fibromyalgia treatment plan established at least 4 weeks prior to dosing. Stable means no change in dose or any pain medication.
• Ability to understand the requirements of the study, provide written informed consent, abide by the study restrictions, and agree to return for the required assessments
• If currently on psychotherapy, it must have been maintained at the same frequency for 4 weeks prior to treatment.

You may not qualify if:

• Unstable doses of allowed antidepressants or muscle relaxants or dosages for any other medical condition.
• Pain due to concurrent autoimmune or inflammatory disease such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, or other chronic widespread pain condition(s) that may confound fibromyalgia pain.
• Psychiatric or cognitive disorder (e.g., current schizophrenia, severe depression, suicidal ideation, dementia, etc.) that the investigator or sponsor considers significant for this study.
• Clinically significant alcohol or other substance abuse within the last 2 years, in the opinion of the investigator.
• Current or recent history of medically inappropriate or illegal use of drugs of abuse including benzodiazepines, opiates, cocaine, cannabinoids, and amphetamines.
• Current treatment with N-methyl-D-aspartate receptor (NMDAR) ligands including ketamine, amantadine, dextromethorphan, memantine, methadone, or dextropropoxyphene.
• Subjects who are pregnant, breast feeding, or planning to become pregnant during the course of the study and for 28 days after the final administration of investigational product.
• Any other serious medical condition affecting heart, lung or any other organ system.
• Any impairment, activity or situation that in the judgment of the investigator would prevent satisfactory completion of the study protocol.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

Related Publications (8)

• Arnold LM, Clauw DJ, Dunegan LJ, Turk DC; FibroCollaborative. A framework for fibromyalgia management for primary care providers. Mayo Clin Proc. 2012 May;87(5):488-96. doi: 10.1016/j.mayocp.2012.02.010.

  PMID: 22560527 BACKGROUND

• Clauw DJ, Arnold LM, McCarberg BH; FibroCollaborative. The science of fibromyalgia. Mayo Clin Proc. 2011 Sep;86(9):907-11. doi: 10.4065/mcp.2011.0206.

  PMID: 21878603 BACKGROUND

• Sorensen J, Bengtsson A, Backman E, Henriksson KG, Bengtsson M. Pain analysis in patients with fibromyalgia. Effects of intravenous morphine, lidocaine, and ketamine. Scand J Rheumatol. 1995;24(6):360-5. doi: 10.3109/03009749509095181.

  PMID: 8610220 BACKGROUND

• Sorensen J, Bengtsson A, Ahlner J, Henriksson KG, Ekselius L, Bengtsson M. Fibromyalgia--are there different mechanisms in the processing of pain? A double blind crossover comparison of analgesic drugs. J Rheumatol. 1997 Aug;24(8):1615-21.

  PMID: 9263160 BACKGROUND

• Noppers I, Niesters M, Swartjes M, Bauer M, Aarts L, Geleijnse N, Mooren R, Dahan A, Sarton E. Absence of long-term analgesic effect from a short-term S-ketamine infusion on fibromyalgia pain: a randomized, prospective, double blind, active placebo-controlled trial. Eur J Pain. 2011 Oct;15(9):942-9. doi: 10.1016/j.ejpain.2011.03.008. Epub 2011 Apr 11.

  PMID: 21482474 BACKGROUND

• Graven-Nielsen T, Kendall SA, Henriksson KG, Bengtsson M, Sorensen J, Johnson A, Gerdle B, Arendt-Nielsen L. Ketamine reduces muscle pain, temporal summation, and referred pain in fibromyalgia patients. Pain. 2000 Apr;85(3):483-491. doi: 10.1016/S0304-3959(99)00308-5.

  PMID: 10781923 BACKGROUND

• Jevtovic-Todorovic V, Todorovic SM, Mennerick S, Powell S, Dikranian K, Benshoff N, Zorumski CF, Olney JW. Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin. Nat Med. 1998 Apr;4(4):460-3. doi: 10.1038/nm0498-460.

  PMID: 9546794 BACKGROUND

• Nagele P, Metz LB, Crowder CM. Nitrous oxide (N(2)O) requires the N-methyl-D-aspartate receptor for its action in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8791-6. doi: 10.1073/pnas.0402825101. Epub 2004 May 24.

  PMID: 15159532 BACKGROUND

MeSH Terms

Conditions

Fibromyalgia; Pain

Interventions

Endothelium-Dependent Relaxing Factors; Inhalation; Nitrous Oxide; salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Vasodilator Agents; Cardiovascular Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Nitrogen Oxides; Gases; Inorganic Chemicals; Nitrogen Compounds; Oxides; Oxygen Compounds

Study Officials

• Peter Nagele, MD, MSc

  University of Chicago, Department of Anesthesia and Critical Care

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Frank Brown Jr

CONTACT

773-834-5778; ftbrownjr@uchicagomedicine.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Patient and assessor blinded to study group assigned
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are randomly assigned to a treatment group schedule, group-1 (nitrous, placebo), or group-2 (placebo, nitrous). Dosing consists of 50% Nitrous oxide in oxygen mixture (FiO2 0.5) vs placebo (oxygen-air mixture FiO2 ≈0.3).

Study Record Dates

• First Submitted: November 9, 2021
• First Posted: May 2, 2022
• Study Start: November 12, 2021
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)