Efficacy of Chemically Distinct Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Pain Phenotypes in Adhesive Capsulitis

Comparative Efficacy of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) With Distinct Chemical Structures in Shoulder Adhesive Capsulitis and the Role of Pain Phenotypes

Patients aged 18-75 years who present to a tertiary rehabilitation hospital with shoulder pain and restricted range of motion, and who consent to participate, will be included in the study. Eligibility will be determined based on predefined inclusion and exclusion criteria.

Eligible patients will be randomly assigned to receive one of several nonsteroidal anti-inflammatory drugs (NSAIDs) with differing chemical properties (e.g., diclofenac, meloxicam, or indomethacin), in combination with a home-based exercise program for shoulder adhesive capsulitis. Patients' sociodemographic data, as well as detailed clinical and examination findings and baseline outcomes, will be recorded. Patients will be informed about their condition, and modifications to activities of daily living will be recommended.Patients' pain phenotypes (nociceptive, neuropathic, nociplastic) will be categorized based on clinical history and questionnaires, and it will be determined which pain types derive greater benefit from NSAIDs.

Follow-up assessments will be conducted at the end of the first and second weeks. At the first-week follow-up, pain intensity will be evaluated using the Visual Analog Scale (VAS). If the treatment is deemed effective (defined as a ≥3-point reduction or ≥50% decrease in VAS), the same NSAID will be continued for an additional week; otherwise, it will be switched to an alternative NSAID with a different biochemical profile (group). The outcomes assessments will be performed by a blinded evaluator to minimize bias.

Study Overview

• Status: Recruiting
• Conditions: Shoulder Pain; Neuropathic Pain; Adhesive Capsulitis; Frozen Shoulder; Nociplastic Pain; NSAID (Non-Steroidal Anti-Inflammatory Drug)
• Intervention / Treatment: Drug: Propionic acid deriaves; Drug: acetic acid derivatives; Drug: oxicam derivatives

Detailed Description

This study will include patients presenting to the Physical Medicine and Rehabilitation outpatient clinics of Konya Beyhekim Training and Research Hospital with shoulder pain and restricted range of motion, who are clinically diagnosed with frozen shoulder following a comprehensive evaluation. All patients will be prescribed non-steroidal anti-inflammatory drugs (NSAIDs) as part of analgesic treatment.

A total of 120 consecutive patients aged 18-75 years, with shoulder pain lasting at least one month and diagnosed with frozen shoulder after appropriate differential diagnosis, who consent to participate, will be enrolled. All participants will provide written informed consent for study participation. Sociodemographic characteristics and clinical examination findings will be recorded for all participants. As part of the clinical examination, patients will be evaluated for diagnosis and differential diagnosis based on the presence of impingement tests, drop arm sign, shoulder ultrasonography (presence of significant effusion, rotator cuff tear), and plain radiography. Following assessment according to predefined inclusion and exclusion criteria, patients will be randomized (block randomization) to receive one of several NSAIDs with distinct chemical properties (e.g., diclofenac, meloxicam, or indomethacin). Patients' sociodemographic data, as well as detailed clinical and examination findings and baseline outcomes, will be recorded. Patients will be informed about their condition, and modifications to activities of daily living will be recommended. Patients' pain phenotypes (nociceptive, neuropathic, nociplastic) will be categorized based on clinical history and questionnaires, and it will be determined which pain types derive greater benefit from NSAIDs.

As a home exercise program, patients will perform range-of-motion exercises, Codman exercises, isometric strengthening, and stretching within their self-limited pain threshold. Exercise adherence will be monitored at the first and second visits, and patients with less than 70% adherence will be excluded.

Patients will be re-evaluated one week after treatment initiation. Pain will be assessed based on perceived pain relief, Visual Analog Scale (VAS; 0-10), and overall treatment effectiveness. Patients demonstrating a clinically meaningful response-defined as at least a 50% reduction in pain or a decrease of ≥3 points on the VAS-will continue the same NSAID for an additional week, provided no adverse effects or contraindications arise. These patients will undergo a final evaluation at the end of the second week. For patients who do not show sufficient improvement at the first-week assessment, the prescribed NSAID will be randomly switched to an alternative NSAID agent with different chemical properties (including both switching within the same chemical class-for example, from diclofenac to etodolac-and switching to a different chemical class with distinct properties-for example, from diclofenac to meloxicam). These patients will continue treatment for an additional week and will be reassessed at the end of the second week, at which point treatment effectiveness will be recorded. After two weeks, the medical treatment and exercise program will be completed, and the outcomes at the end of week 2 will be assessed by a blinded evaluator, marking the completion of the study. In addition, any NSAID-related side effects (dyspepsia, nausea, headache, hypertension, gastrointestinal hemorrhage, etc.) will be recorded, and patient satisfaction (subjective impression of improvement) level will be assessed by a blind investigator using a Likert-type questionnaire (1; not satisfied at all, 5; very satisfied). The study will be concluded once a total of 120 consecutive patients meeting the inclusion criteria have been enrolled.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rukiye Hilal Taygurt Md., principal investigator; Phone Number: +905389122141; Email: rukiyehilalgokce@gmail.com
• Study Contact Backup: Name: furkan taygurt Md., relative; Phone Number: +905512203334; Email: furkantaygurt2@gmail.com

Study Locations

• Turkey (Türkiye)
  • Selçuklu
    • Konya, Selçuklu, Turkey (Türkiye), 42000
      • Recruiting
      • Konya Beyhekim Training and Research Hospital
      • Contact: Konya Beyhekim Training and Research Hospital Physical Therapy and Rehabilitation Center; Phone Number: 4702 0332 224 30 00; Email: konyadhs28@saglik.gov.tr
      • Contact: Rukiye Hilal taygurt Md., principal investigator; Phone Number: 4702 05389122141; Email: rukiyehilalgokce@gmail.com
      • Principal Investigator: Rukiye Hilal Taygurt Md., principal investigator

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Being between 18-75 years of age
2. Having shoulder pain that has lasted for at least one month and being diagnosed with primary frozen shoulder
3. Having a VAS pain level ≥ 4/10
4. Having ≥30 degrees of range of motion restriction in at least two planes (flexion, abduction, or external rotation)
5. Not having any exclusion criteria and agreeing to participate in the study voluntarily

Exclusion Criteria:

1. Patients with a history of shoulder trauma, those with musculoskeletal disorders characterized by pain and loss of function in the affected extremity (such as lateral epicondylitis, flexor tendon injury, de Quervein's tenosynovitis)
2. Presence of neurological involvement such as stroke, brachial plexus injury, Parkinson's disease, and cervical spine injury with or without radiculopathy
3. History of shoulder surgery, malignancy or tumor in the shoulder, those who have undergone shoulder manipulation
4. Presence of shoulder arthritis, rotator cuff tear or other shoulder injuries, thoracic outlet syndrome
5. Systemic disease affecting the shoulder region, severe degeneration or trauma (e.g., osteoarthritis, rheumatoid arthritis, history of labrum or articular cartilage injuries), inflammatory rheumatic diseases
6. Those who have received steroid injections into the affected extremity within the last 3 months, those using oral steroids or NSAIDs, those receiving any surgical or interventional treatment, or Planned individuals:
7. Those who are pregnant or lactating
8. Those with uncontrolled diabetes, heart failure, uncontrolled systemic disease (liver disease, chronic kidney failure, significant endocrine disorders, etc.)
9. Those with communication problems, severe psychiatric disorders
10. Those allergic to NSAIDs or with any contraindications
11. Those with bleeding, coagulation disorders, stomach ulcers, or symptomatic gastritis

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: propionic acid derivatives; Patients will be given oral tablets of ibuprofen or naproxen in this group.	Drug: Propionic acid deriaves; Patients randomized into this group (n=40) will, again by simple randomization, be given oral tablets of ibuprofen or naproxen; Other Names: İbuprofen; naproksen; Home-based exercises
Active Comparator: acetic acid derivatives; Patients will be given oral tablets of etodolac or diclofenac in this group.	Drug: acetic acid derivatives; Patients randomized into this group (n=40) will, again by simple randomization, be given oral tablets of etodolac or diclofenac.; Other Names: diclofenac; etodolac; Home-based exercises
Active Comparator: oxicam derivatives; Patients will be given oral tablets of meloxicam or lornoxicam in this group.	Drug: oxicam derivatives; Patients randomized into this group (n=40) will, again by simple randomization, be given oral tablets of meloxicam or lornoxicam.; Other Names: meloxicam; lornoxicam; Home-based exercises

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VAS pain (0-10) (night and movement)	Visual Analog Scale (VAS) for pain: 0 = no pain, 10 = worst imaginable/unbearable pain.	Baseline, Week 1, and Week 2
Range of motion (ROM)	Movements of the affected shoulder (flexion, abduction, internal and external rotation) will be measured and recorded using a goniometer. The presence of limitation will be assessed by comparing it to the unaffected side.	Baseline, and Week 2
SPADI :Shoulder Pain and Disability Index	The Shoulder Pain and Functionality Index (SPADI) is a self-report scale developed to assess the severity of shoulder pain and its impact on functionality. The scale consists of two sub-sections: pain (5 items) and functionality (8 items). Each item is scored from 0 (no pain or difficulty) to 10 (unbearable pain or extreme difficulty). The total score ranges from 0 to 100; higher scores indicate more severe pain and loss of function.	Baseline, and Week 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DN4 Neuropathic Pain Questionnaire	This is a questionnaire that compiles symptoms and findings associated with neuropathic pain. It is scored on a scale of 0-10. A score above 4 is considered indicative of neuropathic pain.	Baseline
Central Sensitization Inventory	This is a 25-item self-report scale that measures central nervous system hypersensitivity to normal stimuli (central sensitization), a condition that plays a role in the pathophysiology of chronic pain. It aids in diagnosis of chronic pain syndromes such as fibromyalgia by scoring common somatic and emotional symptoms on a scale of 0-100.	Baseline
Sleep Quality Scale	Sleep quality during the preceding week was evaluated using the Single-Item Sleep Quality Scale (SQS), a brief and practical instrument derived from item 6 of the Pittsburgh Sleep Quality Index. The scale evaluates sleep quality using a VAS ranging from 0 to 10, which is then categorized on a 0-4 scale, ranging from 0 (terrible) to 4 (excellent)."	Baseline, and Week 2
Pain Catastrophizing Scale	This is a 13-item self-report questionnaire, scored from 0 to 52, that measures negative cognitive and emotional responses to pain experiences, such as helplessness, exaggeration (magnification), and rumination. It is widely used in chronic pain management and in determining a patient's sensitivity to pain.	Baseline, and Week 2
Patient satisfaction (subjective impression of improvement)	Patient satisfaction subjective evaluation is the measurement of a patient's personal perceptions, feelings, and expectations regarding the healthcare service received, physician communication, hospital environment, and treatment outcomes, through surveys or interviews. Patient satisfaction (subjective impression of improvement) was assessed using a five-point Likert-type scale. Response options were defined as follows: 1, "no satisfaction at all"; 2, "not satisfied"; 3, neutral (no positive or negative effect); 4, "satisfied"; and 5, "very satisfied."	2nd week

Collaborators and Investigators

• Sponsor: Konya Beyhekim Training and Research Hospital
• Investigators: Study Director: Ramazan Yılmaz Associate Professor Dr., advisor, Konya Beyhekim Training and Research Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2026
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): March 30, 2027

Study Registration Dates

• First Submitted: March 19, 2026
• First Submitted That Met QC Criteria: March 19, 2026
• First Posted (Actual): March 25, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: adhesive capsulitis; shoulder pain; exercises; frozen shoulder; pain phenotypes; Nonsteroidal Anti-Inflammatory Drugs
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Neuromuscular Diseases; Joint Diseases; Peripheral Nervous System Diseases; Arthralgia; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Bursitis; Neuralgia; Shoulder Pain; Motor Activity; Nociplastic Pain; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiazoles; Azoles; Carboxylic Acids; Indoles; Acids, Carbocyclic; Thiazines; Phenylacetates; Acids, Heterocyclic; Phenylpropionates; Indoleacetic Acids; Meloxicam; Diclofenac; Ibuprofen; Etodolac; lornoxicam
• Other Study ID Numbers: BeyhekimTRH-RHT2026/5477

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Patient information is confidential.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes