Effects of Photobiomodulation and Topical Diclofenac on Inflammation and Pain in Knee Osteoarthritis (EPIC-KO)

NCT ID: NCT07079969

Last Updated: 2025-11-25

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2026-07-31

Brief Summary

This study aims to compare the effects of combined treatments-dual-wavelength photobiomodulation (PBM) with or without topical diclofenac-on inflammation, pain, and joint function in patients with knee osteoarthritis (OA). It also seeks to determine the synergistic effect of PBM plus topical diclofenac on inflammatory markers, pain scores, and functional outcomes.

Conditions

Knee Pain Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

PBM Only

Participants will receive placebo topical cream (identical in appearance to diclofenac sodium 1% gel), applied at a dose of 4 grams to the affected knee during each treatment session. They will also receive active photobiomodulation therapy (PBM) using an FDA-cleared near-infrared device. PBM will be administered approximately 10 minutes after placebo cream application. Both treatments will be delivered in six sessions over a 2-3 week period, at a frequency of 2-3 times per week.

Group Type: EXPERIMENTAL

Photobiomodulation therapy (PBM) device

Intervention Type: DEVICE

FDA-cleared near-infrared PBM device delivering therapeutic light to the affected knee. Administered once per session, approximately 10 minutes after topical application, in six sessions over 2-3 weeks (2-3 times per week).

Placebo topical cream

Intervention Type: DRUG

Inert cream matching the appearance of diclofenac sodium 1% gel. Applied at 4 grams to the affected knee, once per session, immediately before PBM/sham PBM. Used in six sessions over 2-3 weeks

Diclofenac only

Participants will receive diclofenac sodium 1% topical cream, applied at a dose of 4 grams to the affected knee during each treatment session. They will also receive sham PBM using a device identical in appearance to the active PBM device but without therapeutic light output. Sham PBM will be administered approximately 10 minutes after diclofenac cream application. Both treatments will be delivered in six sessions over 2-3 weeks, at a frequency of 2-3 times per week.

Group Type: EXPERIMENTAL

Sham PBM device

Intervention Type: DEVICE

Identical in appearance to the active PBM device but emits no therapeutic light. Administered once per session, approximately 10 minutes after topical application, in six sessions over 2-3 weeks.

Diclofenac Sodium 1 % Topical Cream

Intervention Type: DRUG

Topical nonsteroidal anti-inflammatory drug applied at a dose of 4 grams to the affected knee, once per session, immediately before PBM/sham PBM. Used in six sessions over 2-3 weeks.

Combined

Participants will receive diclofenac sodium 1% topical cream, applied at a dose of 4 grams to the affected knee during each treatment session. They will also receive active PBM using the same device and parameters described above. PBM will be administered approximately 10 minutes after diclofenac cream application. Both treatments will be delivered in six sessions over 2-3 weeks, at a frequency of 2-3 times per week.

Group Type: EXPERIMENTAL

Photobiomodulation therapy (PBM) device

Intervention Type: DEVICE

FDA-cleared near-infrared PBM device delivering therapeutic light to the affected knee. Administered once per session, approximately 10 minutes after topical application, in six sessions over 2-3 weeks (2-3 times per week).

Diclofenac Sodium 1 % Topical Cream

Intervention Type: DRUG

Topical nonsteroidal anti-inflammatory drug applied at a dose of 4 grams to the affected knee, once per session, immediately before PBM/sham PBM. Used in six sessions over 2-3 weeks.

Double placebo

Participants will receive placebo topical cream, applied at a dose of 4 grams to the affected knee during each treatment session. They will also receive sham PBM using a visually identical device that does not emit therapeutic light. Sham PBM will be administered approximately 10 minutes after placebo cream application. Both treatments will be delivered in six sessions over 2-3 weeks, at a frequency of 2-3 times per week.

Group Type: PLACEBO_COMPARATOR

Sham PBM device

Intervention Type: DEVICE

Identical in appearance to the active PBM device but emits no therapeutic light. Administered once per session, approximately 10 minutes after topical application, in six sessions over 2-3 weeks.

Placebo topical cream

Intervention Type: DRUG

Inert cream matching the appearance of diclofenac sodium 1% gel. Applied at 4 grams to the affected knee, once per session, immediately before PBM/sham PBM. Used in six sessions over 2-3 weeks

Interventions

Photobiomodulation therapy (PBM) device

FDA-cleared near-infrared PBM device delivering therapeutic light to the affected knee. Administered once per session, approximately 10 minutes after topical application, in six sessions over 2-3 weeks (2-3 times per week).

Intervention Type: DEVICE

Sham PBM device

Identical in appearance to the active PBM device but emits no therapeutic light. Administered once per session, approximately 10 minutes after topical application, in six sessions over 2-3 weeks.

Intervention Type: DEVICE

Diclofenac Sodium 1 % Topical Cream

Topical nonsteroidal anti-inflammatory drug applied at a dose of 4 grams to the affected knee, once per session, immediately before PBM/sham PBM. Used in six sessions over 2-3 weeks.

Intervention Type: DRUG

Placebo topical cream

Inert cream matching the appearance of diclofenac sodium 1% gel. Applied at 4 grams to the affected knee, once per session, immediately before PBM/sham PBM. Used in six sessions over 2-3 weeks

Intervention Type: DRUG

Other Intervention Names

light therapy; placebo light therapy; Voltaren; NSAID topical cream; Vehicle cream

Eligibility Criteria

Inclusion Criteria

• Clinically confirmed knee osteoarthritis (OA) based on the American College of Rheumatology (ACR) criteria with symptomatic pain for ≥ 3 months
• Average knee-pain intensity ≥ 30/100 on both the Daily Symptom Diary (DSD) run-in and CATI
• Age ≥ 50 years
• Ability to give informed consent, attend visits, and complete ≥ 4 of 7 DSD entries pre-randomization
• Capacity to perform all study tasks (Timed Up-and-Go, knee OA assessments, blood draw, questionnaires, etc)

Exclusion Criteria

Systemic and Rheumatic Disease

• Active systemic rheumatic condition (e.g., rheumatoid arthritis, systemic lupus erythematosus)
• Fibromyalgia with pain outside the knee that is equal to or worse than knee pain

Musculoskeletal History

• Clinically significant surgery on the index knee (e.g., arthroplasty, osteotomy)
• Knee surgery within the past 6 weeks
• Intra-articular injection to the index knee within the past 14 days

Medication Use

• Daily opioid therapy
• Hypersensitivity or allergy to diclofenac, other NSAIDs, or PBM
• Use of centrally acting sodium-channel blockers or NMDA-receptor antagonists
• New prescription or OTC analgesic, non-pharmacologic pain therapy, investigational drug, chemotherapy, or radiation therapy initiated ≤ 30 days before screening
• Clinically significant drug interaction between topical diclofenac and concomitant medications per Drugs.com Drug Interaction Checker

Cardiovascular Safety

• Uncontrolled hypertension (SBP > 150 mmHg or DBP > 95 mmHg)
• Unstable or activity-limiting cardiovascular or peripheral arterial disease

Neurological and Psychiatric Conditions

• Diagnosed neurological disorder (e.g., Parkinson's disease, multiple sclerosis, epilepsy)
• History or evidence of stroke or moderate-severe traumatic brain injury
• Serious psychiatric illness requiring hospitalization within the past 12 months
• Active suicidal ideation
• Current substance-use disorder or past hospitalization for substance-use treatment

Dermatologic Conditions

• Compromised skin integrity at or near the treatment site (e.g., open wounds, active rash, dermatitis, burns, ulcers, eczema, infection) interfering with topical treatment or PBM

Renal Function

• Severe renal impairment
• History of acute kidney injury within the past 6 months

Hepatic Function

• Active liver disease or elevated liver enzymes
• Known moderate to severe hepatic impairment
• Acute or chronic liver disease such as hepatitis

Other Metabolic Conditions

• Uncontrolled diabetes
• Diabetes-related complications (e.g., peripheral neuropathy, severe nephropathy, chronic ulcers at treatment site)
• Active peptic ulcers or history of recurrent peptic ulcers with complications (e.g., bleeding, perforation)
• Current use of anticoagulants with a history of gastrointestinal ulceration

Other Pain Conditions

• Chronic pain at another body site more severe than knee pain

General Health and Cognition

• Severe circulatory disorder
• Pregnancy or lactation
• Cognitive impairment that precludes informed consent or task participation

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Florida

Gainesville, Florida, United States

Countries

United States

Central Contacts

Selenia Rubio, MD. MBA,

Role: CONTACT

srubio7@ufl.edu

352-273-5590

Facility Contacts

Selenia Rubio, MD., MBA

Role: primary

srubio7@ufl.edu

352-273-5590

Other Identifiers

IRB202501000

Identifier Type: -

Identifier Source: org_study_id