Pregabalin Phonophoresis and MET for Knee Osteoarthritis

NCT07598474 | Recruiting

• 1 other identifier: TUF/EIRB/ 223 /26
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Knee osteoarthritis (OA) is a common condition causing pain, stiffness, and difficulty walking. Many patients with advanced (Grade III) knee OA also experience neuropathic pain - burning, tingling, or electric shock sensations - which is harder to treat with standard physiotherapy. Oral pregabalin works for neuropathic pain but causes side effects like dizziness and drowsiness. This study tests whether delivering pregabalin through the skin using ultrasound (phonophoresis), combined with calf muscle stretching (Muscle Energy Technique), can reduce nerve pain and improve walking better than ultrasound alone.

Conditions

Knee Osteoarthritis

Keywords

Neuropathic Pain; Phonophoresis; Pregabalin; Muscle Energy Technique; Gastrocnemius

Outcome Measures

Primary Outcomes (1)

• Change in Neuropathic Pain Component

  Douleur Neuropathique 4 (DN-4) questionnaire. A validated 4-question (7-item) screening tool for neuropathic pain. Questions 1-2: patient interview regarding pain characteristics (burning, painful cold, electric shocks, tingling, pins and needles, numbness, itching). Questions 3-4: physical examination (hypoesthesia to touch, hypoesthesia to pinprick, brushing-evoked pain). Each item scored 0 (no) or 1 (yes). Total score range 0-10. A score ≥4 indicates presence of neuropathic pain component. Higher scores indicate greater neuropathic pain. Minimal clinically important difference for DN-4 in osteoarthritis: 2 points.

  Baseline (week 0, pre-intervention) and Week 4 (post-intervention, after 16 sessions)

Secondary Outcomes (2)

• Change in Pain Intensity

  Baseline (week 0, pre-intervention) and Week 4 (post-intervention, after 16 sessions)

• Change in Functional Mobility and Stiffness

  Baseline (week 0, pre-intervention) and Week 4 (post-intervention, after 16 sessions)

Study Arms (2)

Group A: Pregabalin Phonophoresis + Gastrocnemius MET

EXPERIMENTAL

Participants assigned to Group A receive pregabalin-encapsulated hydrogel phonophoresis followed by gastrocnemius muscle energy technique (post-isometric relaxation). Protocol: Hot pack (10 min), phonophoresis with pregabalin hydrogel (1 MHz, 1 W/cm², continuous, 5 min, circular application over knee), MET for gastrocnemius (7-10 sec isometric contraction followed by 10 sec stretch, repeated 4-5 times). Four sessions per week for four weeks (total 16 sessions).

Combination Product: Pregabalin-Encapsulated Hydrogel Phonophoresis; Other: Gastrocnemius Muscle Energy Technique (Post-Isometric Relaxation)

Group B: Aqua Gel Phonophoresis + Gastrocnemius MET

ACTIVE COMPARATOR

Participants assigned to Group B receive aqua gel (non-medicated ultrasound gel) phonophoresis followed by gastrocnemius muscle energy technique (post-isometric relaxation). Protocol: Hot pack (10 min), phonophoresis with aqua gel (1 MHz, 1 W/cm², continuous, 5 min, circular application over knee), MET for gastrocnemius (7-10 sec isometric contraction followed by 10 sec stretch, repeated 4-5 times). Four sessions per week for four weeks (total 16 sessions).

Other: Gastrocnemius Muscle Energy Technique (Post-Isometric Relaxation); Device: Aqua Gel Phonophoresis

Interventions

Pregabalin-Encapsulated Hydrogel Phonophoresis COMBINATION_PRODUCT

Pregabalin (5% w/w) incorporated into a water-soluble, ultrasound-conductive gel base. Delivered via therapeutic ultrasound (Sonopuls 490, Enraf-Nonius) with parameters: continuous mode, frequency 1 MHz, intensity 1 W/cm², treatment duration 5 minutes, sound head moved in slow circular motion (2-3 cm/sec) over medial, lateral, and posterior knee regions. Approximately 0.5 mL of gel per cm² per session. Administered 4 sessions/week for 4 weeks (total 16 sessions). Prepared under sterile conditions, stored at 4°C, used within 14 days.

Group A: Pregabalin Phonophoresis + Gastrocnemius MET

Gastrocnemius Muscle Energy Technique (Post-Isometric Relaxation) OTHER

Manual therapy technique performed with participant supine, legs extended. Therapist stabilizes distal femur and holds plantar foot. Participant performs plantarflexion isometric contraction against therapist resistance at \~25% maximum effort for 7-10 seconds (no joint movement). After relaxation, therapist passively dorsiflexes ankle to first point of tissue resistance (mild stretch, never pain) and holds for 10 seconds. Cycle repeated 4-5 times per session. Preceded by 10-minute hot pack application. Performed 4 sessions/week for 4 weeks (total 16 sessions).

Group A: Pregabalin Phonophoresis + Gastrocnemius MET; Group B: Aqua Gel Phonophoresis + Gastrocnemius MET

Aqua Gel Phonophoresis DEVICE

Standard ultrasound conductive gel containing water, carbomer, propylene glycol, methylparaben, propylparaben (no active pharmaceutical ingredient). Delivered via therapeutic ultrasound (Sonopuls 490, Enraf-Nonius) with parameters: continuous mode, frequency 1 MHz, intensity 1 W/cm², treatment duration 5 minutes, sound head moved in slow circular motion (2-3 cm/sec) over medial, lateral, and posterior knee regions. Administered 4 sessions/week for 4 weeks (total 16 sessions).

Group B: Aqua Gel Phonophoresis + Gastrocnemius MET

Eligibility Criteria

• Age: 40 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosed Grade III knee osteoarthritis confirmed by Kellgren-Lawrence grading scale (radiograph within past 12 months or newly obtained).
• Neuropathic pain component confirmed by DN-4 questionnaire (score ≥4).
• Age between 40 and 70 years inclusive.
• Both male and female participants.
• Unilateral or bilateral knee involvement (if bilateral, the more symptomatic knee selected for assessment and treatment).
• Willing and able to provide written informed consent.
• Available to attend 4 sessions per week for 4 consecutive weeks (total 16 sessions).
• Able to understand and follow verbal instructions (for MET).

You may not qualify if:

• Diabetic neuropathy (diagnosed or DN-4 score attributable to diabetes rather than knee OA).
• Active skin lesions, wounds, infections, or dermatitis on the knee or calf.
• Metal implants (including knee replacement), pacemaker, or other electronic implant (contraindications for ultrasound).
• Received intra-articular knee injection (corticosteroid or hyaluronic acid) within the last 3 months.
• Grade I, II, or IV knee osteoarthritis (Kellgren-Lawrence).
• Aseptic arthritis of knee (rheumatoid, psoriatic, gouty).
• Any lower extremity deformity (genu varum \>15°, genu valgum \>15°, fixed flexion deformity \>15°).
• Previous knee replacement surgery (partial or total).
• Known allergy or hypersensitivity to pregabalin, gabapentin, or any gel components.
• Pregnant or lactating women (ultrasound safety in pregnancy not established for non-obstetric use).
• Concurrent participation in another interventional study.
• Diagnosis of fibromyalgia, complex regional pain syndrome, or other centralized pain disorder that might confound neuropathic pain assessment.
• Active malignancy or history of knee malignancy.
• Deep vein thrombosis or thrombophlebitis in lower limb.

Sponsors & Collaborators

• University of Faisalabad: lead

Study Sites (1)

The University of Faisalabad

Faisalābad, Punjab Province, 3800, Pakistan

RECRUITING

MeSH Terms

Conditions

Osteoarthritis, Knee; Neuralgia

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Dr. Muhammad Muneeb Jafar, Doctor of Physical Therapy

CONTACT

+92 312 7000616; muneebjafar.DPT@tuf.edu.pk

Dr Muhammad Ateeb, PhD Public Health

CONTACT

+923357333383; mateeb.oric@tuf.edu.pk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Department of Rehabilitation Sciences

Study Record Dates

• First Submitted: May 13, 2026
• First Posted: May 20, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): July 19, 2026
• Study Completion (Estimated): July 19, 2026
• Last Updated: May 20, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)