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

Konya Beyhekim Training and Research Hospital

Status: Enrolling

Conditions: NSAID (Non-Steroidal Anti-Inflammatory Drug); Shoulder Pain; Neuropathic Pain; Frozen Shoulder; Nociplastic Pain; Adhesive Capsulitis

Treatments: Drug: oxicam derivatives; Drug: acetic acid derivatives; Drug: Propionic acid deriaves

Study type: Interventional

Funder types: Other

Identifiers

NCT07493226

BeyhekimTRH-RHT2026/5477

Details and patient eligibility

About

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.

Full 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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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120 participants in 3 patient groups

propionic acid derivatives

Active Comparator group

Description:

Patients will be given oral tablets of ibuprofen or naproxen in this group.

Treatment:

Drug: Propionic acid deriaves

acetic acid derivatives

Active Comparator group

Description:

Patients will be given oral tablets of etodolac or diclofenac in this group.

Treatment:

Drug: acetic acid derivatives

oxicam derivatives

Active Comparator group

Description:

Patients will be given oral tablets of meloxicam or lornoxicam in this group.

Treatment:

Drug: oxicam derivatives