Repetitive Transcranial Magnetic Stimulation Associated With Manual Therapy in Knee Ostearthritis Pain

Phase 2

• Conditions: Knee Osteoarthritis
• Interventions: Device: TMS; Other: Manual therapy (MT)

• Registration Number: NCT03076294
• Lead Sponsor: Universidade Federal de Pernambuco

Brief Summary

In this study, the investigators wondered whether the association between high frequency repetitive transcranial magnetic stimulation (hf-rTMS) and manual therapy (peripheral and central approach) is more effective in reducing pain levels and modulation of cortical activity of chronic knee ostearthritis pain subjects than manual therapy alone (usual peripheral approach). For this purpose, patients included will be submitted to one session with active or sham hf-rTMS followed by a protocol of manual therapy. Besides that another active group will have the sequence of interventions exchanged (manual therapy followed by hf-rTMS) in order to investigate whether this may influence in the final outcomes.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-01
• Status Verified: 2017-03
• Study First Submitted: 2017-03-06
• Study First Submitted QC: 2017-03-06
• Last Update Submitted: 2017-03-06
• Study First Posted: 2017-03-10
• Last Update Posted: 2017-03-10
• Primary Completion: 2018-03
• Study Completion: 2019-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• Diagnosis of knee OA;
• Absence of severe cognitive deficiency verified by the Mini Mental State Examination;
• Meet the American College of Rheumatology criteria for idiopathic knee osteoarthritis.

Exclusion Criteria

• Individuals diagnosed with osteoporosis, fibromyalgia or other neurological disease;
• Had an opioid or corticosteroid injection in the last 30 days;
• Modified chronic pain medication in the last month before participating in the study;
• History of knee surgery in the last six months;
• Obese;
• Contraindications to the use of non-invasive brain stimulation, such as: metal implant on face or skull, history of seizure, cochlear implant.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MT after rTMS group	Manual therapy (MT)	High frequency TMS will be applied with an eight-shaped coil angled at zero degrees from the sagittal axis and positioned at the C3 or C4 in accordance with the international 10-20 marking system (JASPER, 1958), which corresponds to the right or left primary motor cortex (M1). Twenty four stimulus trains will be provided at 10 Hz for five seconds each. The interval between the trains will be 25 seconds, totaling 1200 pulses for approximately 12 minutes, with 90% of resting motor threshold (RMT). After TMS, patients will be submitted to 45 minutes of manual therapy protocol.
rTMS after MT group	Manual therapy (MT)	Patients will be submitted to 45 minutes of manual therapy protocol. After that, high frequency TMS will be applied with an eight-shaped coil angled at zero degrees from the sagittal axis and positioned at the C3 or C4 in accordance with the international 10-20 marking system (JASPER, 1958), which corresponds to the right or left primary motor cortex (M1). Twenty four stimulus trains will be provided at 10 Hz for five seconds each. The interval between the trains will be 25 seconds, totaling 1200 pulses for approximately 12 minutes, with 90% of resting motor threshold (RMT).
MT after rTMS group	TMS	High frequency TMS will be applied with an eight-shaped coil angled at zero degrees from the sagittal axis and positioned at the C3 or C4 in accordance with the international 10-20 marking system (JASPER, 1958), which corresponds to the right or left primary motor cortex (M1). Twenty four stimulus trains will be provided at 10 Hz for five seconds each. The interval between the trains will be 25 seconds, totaling 1200 pulses for approximately 12 minutes, with 90% of resting motor threshold (RMT). After TMS, patients will be submitted to 45 minutes of manual therapy protocol.
rTMS after MT group	TMS	Patients will be submitted to 45 minutes of manual therapy protocol. After that, high frequency TMS will be applied with an eight-shaped coil angled at zero degrees from the sagittal axis and positioned at the C3 or C4 in accordance with the international 10-20 marking system (JASPER, 1958), which corresponds to the right or left primary motor cortex (M1). Twenty four stimulus trains will be provided at 10 Hz for five seconds each. The interval between the trains will be 25 seconds, totaling 1200 pulses for approximately 12 minutes, with 90% of resting motor threshold (RMT).
Control group	TMS	In this group, the order of interventions will be randomized. Therefore, the volunteer can start with manual therapy or sham TMS. In manual therapy, patients will be submitted to 45 minutes of a protocol. In addition, with regard to sham TMS, the same parameters will be used, however, it will be performed using two coils, one connected to the magnetic stimulator, away from the patient's scalp and another uncoupled from the stimulator and positioned in the same way as in real stimulation.
Control group	Manual therapy (MT)	In this group, the order of interventions will be randomized. Therefore, the volunteer can start with manual therapy or sham TMS. In manual therapy, patients will be submitted to 45 minutes of a protocol. In addition, with regard to sham TMS, the same parameters will be used, however, it will be performed using two coils, one connected to the magnetic stimulator, away from the patient's scalp and another uncoupled from the stimulator and positioned in the same way as in real stimulation.

Primary Outcome Measures

Name	Time	Method
Pain Rating Scale (NPRS)	Until 30 days (before, after the interventions and until the last day with the same value of the first evaluation)	Is it used to quantify pain level, where 0 means no pain and 10 means worst pain possible. NPRS is recommended as the main endpoint in chronic pain studies and it has been established that a decrease of at least 2 points or 30% represents a minimal clinically important difference. The MDCI consists of the smaller variation in a clinical outcome perceived by the patient and that results in a relevant change in his state of health.
Pain	Until one day (before and after the interventions)	Pain will be evaluated by pressure algometry before and after the interventions. It's a evaluation technique which aims to quantify through physical stimulation (pressure in the nociceptors) the capacity of pain perception and toleration. It will be used with the patient lying in supine and will have the purpose of measure the pressure pain threshold (PPT) in eight points around patellar region. Besides that, two control points will be adopted, one in anterior tibial muscle (five centimeters distal of anterior tibial tuberosity) and another in the extensor carpi radialis longus muscle (five centimeters distal to lateral humerus epicondyle). After marking, the algometer will be setted up 90° in contact with the skin and will be applied a 0,3 kgf/cm²/s pressure until the patient report pain by pressing a pen (Model/Brand: Algomed/Medoc). The measure will be done twice in the demarcated points with a two minutes interval between them. Will be considered a mean of the obtained values.

Secondary Outcome Measures

Name	Time	Method
Cortical excitability	One day (before and after the interventions)	The motor evoked potential (MEP) will be provided by twenty unconditioned stimuli (120% of motor resting threshould).

Trial Locations

Locations (2)

Applied Neuroscience Laboratory, Universidade Federal de Pernambuco; 🇧🇷 Recife, PE, Brazil

Kinesiotherapy and manual therapeutic resources laboratory; 🇧🇷 Recife, PE, Brazil