Effectiveness of an Oxygen-nitrous Oxide Mixture During Physical Therapy for Frozen Shoulder (MEOPA)

Comparative Study of the Effectiveness of an Equimolar Oxygen-nitrous Oxide Mixture During Physical Therapy for Adhesive Shoulder Capsulitis

The purpose of this study is to determine whether or not the use of an equimolar mixture of oxygen and nitrous oxide during the physical therapy for patients suffering from frozen shoulder (adhesive shoulder capsulitis) results in a gain in shoulder amplitude (Constant Score) and less pain as compared to patients undergoing physical therapy without this treatment.

Study Overview

• Status: Completed
• Conditions: Adhesive Capsulitis
• Intervention / Treatment: Drug: equimolar oxygen-nitrous oxide mixture; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63118
    • Chu de Clermont Ferrand
  • Montpellier, France, 34295
    • CHU Lapeyronie
  • Vallauris, France, 06223
    • Centre Hélio Marin
  • Gard
    • Le Grau-du-Roi, Gard, France, 30240
      • Unité Rééducation Réadaptation Locomotrice
    • Nîmes, Gard, France, 30029
      • Centre Hospitalier Universitaire de Nīmes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Affiliated with a social security system
• Has signed the consent form
• Patient has a painful, or initially painful but stable frozen shoulder (adhesive capsulitis): stiffening characterized by a passive loss of amplitude on three planes. This loss of amplitude is greater than or equal to 50% of controlateral amplitude when the controlateral shoulder is considered as normal. Otherwise, the loss of amplitude is greater than or equal to 50% of normal anatomical values.
• Radiography confirms the integrity of the glenohumeral interspace.

Exclusion Criteria:

• Intercurrent, evolving or unstable pathology: cancer, advanced cardio-vascular pathology, severe infection
• The patient is taking a treatment that may interfere with the study (eg corticoids, pain killers, chemotherapy)
• Contra-indication for physical therapy
• Coagulopathy
• Advanced diabetes mellitus, with neurological or joint complications
• Contra indication for the experimental treatment
• Pregnant or nursing women
• Patient's mental state prevents him/her from understanding the nature of the study, its objectives and potential consequences.
• Patient under guardianship
• Patient is in an exclusion period determined by a previous study
• Patient not able to follow protocol constraints or timetable
• Medical history of local infection, polyarthritis or neuropathy that might explain the shoulder pain.
• Absence of radiculopathy of cervical origin, of rotator cuff tears or evolving shoulder tendinopathy, of severe omarthrose

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: equimolar oxygen-nitrous oxide mixture; equimolar oxygen-nitrous oxide mixture Kinesitherapy is performed with a mask by which patient inhales an equimolar oxygen-nitrous oxide mixture.	Drug: equimolar oxygen-nitrous oxide mixture; Kinesitherapy is performed with a mask by which patient inhales an equimolar oxygen-nitrous oxide mixture.
Placebo Comparator: Placebo; Patients randomized to this arm will have the placebo.	Drug: Placebo; Kinesitherapy is performed with a mask by which patient inhales a placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Constant Score using treatment as compared to without treatment.	The Constant score questionnaire consists of 11 questions that result in a final score ranging from 0 to 100. The higher the test result, the more normally the shoulder is functioning.	fifteen days of physical therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in kinetics at final session since baseline of passive glenohumeral flexion of the shoulder	Range of motion in degrees	Final session on Day 15
Change in kinetics at final session since baseline of passive glenohumeral abduction of the shoulder	Range of motion in degrees	Final session on Day 15
Change in kinetics at final session since baseline of passive glenohumeral external rotation (ER1) of the shoulder	Range of motion in degrees	Final session on Day 15
Change in kinetics at final session since baseline of active global anterior flexion of the shoulder	Range of motion in degrees	Final session on Day 15
Change in kinetics at final session since baseline of active global lateral flexion of the shoulder	Range of motion in degrees	Final session on Day 15
Change in kinetics at final session since baseline of active global abduction of the shoulder	Range of motion in degrees	Final session on Day 15
Change in kinetics at final session since baseline of active global external rotation (ER2) of the shoulder	Range of motion in degrees	Final session on Day 15
Change in kinetics at final session since baseline of active global internal rotation of the shoulder	Range of motion in degrees	Final session on Day 15
Change in kinetics at final session since baseline of passive global anterior flexion of the shoulder	Range of motion in degrees	Final session on Day 15
Change in kinetics at final session since baseline of passive global lateral flexion of the shoulder	Range of motion in degrees	Final session on Day 15
Change in kinetics at final session since baseline of passive global abduction of the shoulder	Range of motion in degrees	Final session on Day 15
Change in kinetics at final session since baseline of passive global external rotation (ER2) of the shoulder	Range of motion in degrees	Final session on Day 15
Pain at visits	0-100 visual analogue scale (VAS)	At each session: final session on Day 15
Pain induced during sessions	0-100 visual analogue scale (VAS)	At each session: final session on Day 15
Functional improvement	Disabilities of the Arm Shoulder and Hand scale (DASH)	Day 7
Functional improvement	Disabilities of the Arm Shoulder and Hand scale (DASH)	Day 15
Functional improvement	Disabilities of the Arm Shoulder and Hand scale (DASH)	Day 45
Functional improvement	Disabilities of the Arm Shoulder and Hand scale (DASH)	Day 180
Limitations posed to the physiotherapist activity due to patient pain at each session	Likert six-point scale (none, to extremely high)	At each session: final session on Day 15
patient satisfaction	0-10 VAS: 10=session interrupted due to pain; 0= session completed under perfect conditions	At each session: final session on Day 15
Change in the Constant Score using treatment as compared to without treatment		Day 7
Change in the Constant Score using treatment as compared to without treatment		Day 45
Change in the Constant Score using treatment as compared to without treatment		Day 180
Patient Quality of life	Medical Outcome Study Short Form-36 (MOS-SF36) score	Day 1
Patient Quality of life	MOS-SF36 score	Day 7
Patient Quality of life	MOS-SF36 score	Day 15
Patient Quality of life	MOS-SF36 score	Day 45
Patient Quality of life	MOS-SF36 score	Day 180
Antalgic intake	Discriptively noted	Until end of study (Day 180)

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: Arnaud Dupeyron, MD, Centre Hospitalier Universitaire de Nīmes

Publications and helpful links

General Publications

• Dupeyron A, Denarie M, Richard D, Dobija L, Castelli C, Petiot S, Tavares I, Gelis A, Coudeyre E. Analgesic gas for rehabilitation of frozen shoulder: Protocol for a randomized controlled trial. Ann Phys Rehabil Med. 2019 Jan;62(1):43-48. doi: 10.1016/j.rehab.2018.07.007. Epub 2018 Aug 9.
• Dupeyron A, Dobija L, Castelli C, Petiot S, Tavares I, Gelis A, Coudeyre E. Nitrous oxide provided during intensive physiotherapy for shoulder adhesive capsulitis does not improve function: A randomised controlled trial. Ann Phys Rehabil Med. 2024 Apr;67(3):101803. doi: 10.1016/j.rehab.2023.101803. Epub 2023 Dec 19.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): September 2, 2013
• Study Completion (Actual): September 2, 2013

Study Registration Dates

• First Submitted: March 15, 2010
• First Submitted That Met QC Criteria: March 15, 2010
• First Posted (Estimated): March 16, 2010

Study Record Updates

• Last Update Posted (Estimated): November 19, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Joint Diseases; Bursitis; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Anesthetics, Inhalation; Nitrous Oxide
• Other Study ID Numbers: PHRC-I/2008/AD-01; 2008-007161-23 (EudraCT Number)