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临床试验/NCT03944889
NCT03944889已完成早期 1 期

Quantitative Response of Healthy Muscle Following the Induction of Capsaicin

Toronto Rehabilitation Institute1 个研究点 分布在 1 个国家目标入组 20 人开始时间: 2019年7月1日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
早期 1 期
状态
已完成
入组人数
20
试验地点
1
主要终点
Motor Unit Action Potential Firing Rate

研究概览

简要总结

Central Sensitization is an aspect of chronic pain and is associated with over-excitability of the central nervous system. Central Sensitization normally presents itself with other chronic syndromes such as Myofascial Pain Syndrome, so it is difficult to separate the characteristics of the two. The purpose of this study is to determine whether sensitizing healthy muscle using capsaicin, a chilli pepper extract, induces a regional change in ultrasound texture features of the targeted muscle, or the muscles in that are in close proximity. This regional change will be accompanied by electromyography (EMG) recordings to confirm the presence of abnormality. Topical capsaicin and injectable capsaicin will be applied at three different concentrations, 0ug(placebo effect),50ug and 100ug.

Research Questions:

Does sensitization cause a significant regional change in the texture features of the targeted muscle or surrounding muscles? Is this regional change confirmed by abnormality of motor unit firing rates or EMG amplitudes? Is the response dose dependent? Does the induced central sensitization cause a change in force steadiness?

Experimental Protocol:

The physician on site will apply surface and intramuscular EMG sensors to the trapezius. A goniometer will be placed on the subjects arm to detect position. Following this, an ultrasound image of the trapezius, supraspinatus and infraspinatus will be taken.The participant will perform an increasing and decreasing contraction.The subject will then have capsaicin injected into their trapezius or applied onto their skin. The exercise and measurements will then be repeated. The ultrasound will be acquired by the Sonosite ultrasound system. The EMG data will be acquired by the Delsys Trigno EMG system for the surface EMG and the Cadwell Sierra Wave system for the intramuscular EMG. The data will be processed through Delsys EMGworks software and MATLAB. Texture features of the pre and post injection ultrasound images will be compared. Decomposition of motor units will allow for the analysis of motor unit action potential firing rate and amplitudes. Analysis of force steadiness will also be calculated via the goniometer.

Overall, the findings from this study should present preliminary evidence to inform central sensitization's effects on regional muscle structure changes, functional changes and motor unit activity.

详细描述

Myofascial pain syndrome (MPS) is a prevalent chronic pain disorder primarily characterized by myofascial trigger points (MTrP). There is limited knowledge on the pathophysiology and mechanisms underlying MTrP and its development. Ultrasound investigations that have been performed on trigger points can differentiate between active and latent trigger points, but have not characterized the central sensitization aspect of them. The electromyography (EMG) investigations of central sensitization that have been performed mostly use hypertonic saline to induce hyperalgesia, and have demonstrated conflicting results. Central sensitization has been proposed as the primary mechanism underlying MTrP development. Central sensitization is associated with hyperexcitability of neuronal responses to normal or noxious stimuli. There is a need for a study that quantifies regional central sensitization using ultrasound to measure the changing structure, and electromyography to measure specific motor unit activity responses in the muscle.

Purpose The purpose of this study is to determine whether sensitizing healthy muscle using capsaicin induces a change in the structural integrity of the affected muscle, and determine if the motor unit frequency and amplitudes change within that region. Central sensitization will be induced using topical capsaicin and injectable capsaicin at three different concentrations. This is an exploratory trial that aims to provide preliminary evidence on whether central sensitization is a direct cause of taut band and MTrP development.

Our specific research questions are followings:

  1. Does sensitization cause a significant regional change in the texture features of the targeted muscle or surrounding muscles?
  2. Does capsaicin induced sensitization elicit a change in motor unit action potential(MUAP) amplitude by approximately 20 to 25% within the region of experimentally induced central sensitization or in the region of texture feature changes? Our hypothesis for this portion of the study is that sensitization modifies the anterior horn cell activity which will be measured by the amplitude of the potentials.
  3. Does capsaicin induced sensitization elicit continuous electrical activity as observed in MTrPs? This tests the hypothesis that sensitization creates the presence of continuous low amplitude action potentials.
  4. Does capsaicin induced sensitization influence the rate of recruitment of motor units in the muscle within the region induced? Does this occur within the regions identified by the changes in texture features? The recruitment of motor units is normally expected to follow the Henneman size principle.[20-23] Our hypothesis for this portion of the study is that sensitization will cause an aberration in recruitment. If this is demonstrated, then there is modification of the normal processing at both dorsal and ventral horns of the spinal cord.
  5. Is there a location dependent EMG response to capsaicin induced sensitization? In other words, do the texture features or EMG responses from muscles that lie anatomically distant from the location of the site of intramuscular capsaicin injection have changes from their baseline calculations? This would test the hypothesis that type III and IV afferents have an influence on the anterior horn cells that lie distant to the ones that are supplying muscle fibers in the vicinity of the stimulated sensory afferents.
  6. Is there a dose dependent EMG response at motor units to capsaicin induced sensitization? Here, the hypothesis of causality will be assessed in a preliminary manner. If there is a relationship then further experiments that more thoroughly assess causality will be needed.

This proposed study is a single centered, factorial, randomized placebo-controlled trial with two independent variables, depth of capsaicin application(3 levels) and dose of capsaicin(3 levels), for a total of 6 treatment arms and three control groups.The first between groups variable will be topical capsaicin application, injectable(intrafascial) and injectable(intramuscular) capsaicin injection. Within each partition, there will be three treatments: control, 50 micrograms, 100 micrograms. The control group will receive a topical skin lotion that is inert and has no sensitization effect. An equal number of participants will be allocated to each of the six treatment groups using an electronic randomization generator. Block randomization will be used to ensure equal allotment into each group.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Factorial
主要目的
Basic Science
盲法
Single (Participant)

盲法说明

Participants and investigators will be blinded to the delivered dose; however, the type of capsaicin delivery cannot be blinded from either participants or investigators. The member of the research team conducting the randomization schedule and concealing allocation will have knowledge of and keep track of the doses contained in the containers and vials of the topical and injectable capsaicin, respectively. They will deliver the appropriate dose to the team member implementing the experimental protocol to ensure there is blinding with respect to dose.

入排标准

年龄范围
18 Years 至 64 Years(Adult)
性别
All
接受健康志愿者

入选标准

  • healthy with no past medical history
  • a visual analogue score below 3 indicating low pain severity, ideally who complain of no pain
  • right or left handed
  • normal body mass index
  • have sufficient knowledge of the English language to provide informed consent and understand the protocols
  • agree to sign a consent form.

排除标准

  • history of pain
  • detectable myofascial trigger points upon physical examination
  • history of pain related disturbances such as poor sleep
  • cognitive disturbances, psychiatric disorders
  • history of general medical disorder that may affect the outcome of the study such as diabetes mellitus
  • history of cervical radiculopathies
  • history of inflammatory arthropathy

研究组 & 干预措施

Placebo Topical

Placebo Comparator

Placebo Cream, applied topically to trapezius muscle

干预措施: Goniometer (Device)

Placebo, Intrafascial

Placebo Comparator

Injection placebo(saline)- injected intrafascially into trapezius

干预措施: Goniometer (Device)

Placebo Topical

Placebo Comparator

Placebo Cream, applied topically to trapezius muscle

干预措施: Delsys Trigno Galileo System (Device)

Placebo Topical

Placebo Comparator

Placebo Cream, applied topically to trapezius muscle

干预措施: Cadwell Sierra Wave (Device)

Placebo Topical

Placebo Comparator

Placebo Cream, applied topically to trapezius muscle

干预措施: Sonosite Ultrasound Machine (Device)

Low Dose, Topical

Active Comparator

Capsaicin Cream- low dosage, applied topically to trapezius

干预措施: Capsaicin (Drug)

Low Dose, Topical

Active Comparator

Capsaicin Cream- low dosage, applied topically to trapezius

干预措施: Delsys Trigno Galileo System (Device)

Low Dose, Topical

Active Comparator

Capsaicin Cream- low dosage, applied topically to trapezius

干预措施: Cadwell Sierra Wave (Device)

Low Dose, Topical

Active Comparator

Capsaicin Cream- low dosage, applied topically to trapezius

干预措施: Sonosite Ultrasound Machine (Device)

Low Dose, Topical

Active Comparator

Capsaicin Cream- low dosage, applied topically to trapezius

干预措施: Goniometer (Device)

High Dose, Topical

Active Comparator

Capsaicin Cream- higher dosage, applied topically to trapezius

干预措施: Capsaicin (Drug)

High Dose, Topical

Active Comparator

Capsaicin Cream- higher dosage, applied topically to trapezius

干预措施: Delsys Trigno Galileo System (Device)

High Dose, Topical

Active Comparator

Capsaicin Cream- higher dosage, applied topically to trapezius

干预措施: Cadwell Sierra Wave (Device)

High Dose, Topical

Active Comparator

Capsaicin Cream- higher dosage, applied topically to trapezius

干预措施: Sonosite Ultrasound Machine (Device)

High Dose, Topical

Active Comparator

Capsaicin Cream- higher dosage, applied topically to trapezius

干预措施: Goniometer (Device)

Placebo, Intrafascial

Placebo Comparator

Injection placebo(saline)- injected intrafascially into trapezius

干预措施: Delsys Trigno Galileo System (Device)

Placebo, Intrafascial

Placebo Comparator

Injection placebo(saline)- injected intrafascially into trapezius

干预措施: Cadwell Sierra Wave (Device)

Placebo, Intrafascial

Placebo Comparator

Injection placebo(saline)- injected intrafascially into trapezius

干预措施: Sonosite Ultrasound Machine (Device)

Low Dose, Intrafacial

Active Comparator

Injection Capsaicin formulation low dose- injected intrafascially into trapezius

干预措施: Capsaicin (Drug)

Low Dose, Intrafacial

Active Comparator

Injection Capsaicin formulation low dose- injected intrafascially into trapezius

干预措施: Delsys Trigno Galileo System (Device)

Low Dose, Intrafacial

Active Comparator

Injection Capsaicin formulation low dose- injected intrafascially into trapezius

干预措施: Cadwell Sierra Wave (Device)

Low Dose, Intrafacial

Active Comparator

Injection Capsaicin formulation low dose- injected intrafascially into trapezius

干预措施: Sonosite Ultrasound Machine (Device)

High Dose, Intramuscular

Active Comparator

Injection Capsaicin formulation higher dose - injected intramuscularly into trapezius

干预措施: Cadwell Sierra Wave (Device)

Low Dose, Intrafacial

Active Comparator

Injection Capsaicin formulation low dose- injected intrafascially into trapezius

干预措施: Goniometer (Device)

High Dose, Intrafascial

Active Comparator

Injection Capsaicin formulation higher dose- injected intrafascially into trapezius

干预措施: Capsaicin (Drug)

Low Dose, Intramuscular

Active Comparator

Injection Capsaicin formulation low dose - injected intramuscularly into trapezius

干预措施: Capsaicin (Drug)

High Dose, Intrafascial

Active Comparator

Injection Capsaicin formulation higher dose- injected intrafascially into trapezius

干预措施: Delsys Trigno Galileo System (Device)

High Dose, Intrafascial

Active Comparator

Injection Capsaicin formulation higher dose- injected intrafascially into trapezius

干预措施: Cadwell Sierra Wave (Device)

High Dose, Intrafascial

Active Comparator

Injection Capsaicin formulation higher dose- injected intrafascially into trapezius

干预措施: Sonosite Ultrasound Machine (Device)

High Dose, Intrafascial

Active Comparator

Injection Capsaicin formulation higher dose- injected intrafascially into trapezius

干预措施: Goniometer (Device)

Placebo, Intramuscular

Placebo Comparator

Injection placebo (saline) - injected intramuscularly into trapezius

干预措施: Delsys Trigno Galileo System (Device)

Placebo, Intramuscular

Placebo Comparator

Injection placebo (saline) - injected intramuscularly into trapezius

干预措施: Cadwell Sierra Wave (Device)

Placebo, Intramuscular

Placebo Comparator

Injection placebo (saline) - injected intramuscularly into trapezius

干预措施: Sonosite Ultrasound Machine (Device)

Placebo, Intramuscular

Placebo Comparator

Injection placebo (saline) - injected intramuscularly into trapezius

干预措施: Goniometer (Device)

Low Dose, Intramuscular

Active Comparator

Injection Capsaicin formulation low dose - injected intramuscularly into trapezius

干预措施: Delsys Trigno Galileo System (Device)

Low Dose, Intramuscular

Active Comparator

Injection Capsaicin formulation low dose - injected intramuscularly into trapezius

干预措施: Cadwell Sierra Wave (Device)

Low Dose, Intramuscular

Active Comparator

Injection Capsaicin formulation low dose - injected intramuscularly into trapezius

干预措施: Sonosite Ultrasound Machine (Device)

Low Dose, Intramuscular

Active Comparator

Injection Capsaicin formulation low dose - injected intramuscularly into trapezius

干预措施: Goniometer (Device)

High Dose, Intramuscular

Active Comparator

Injection Capsaicin formulation higher dose - injected intramuscularly into trapezius

干预措施: Capsaicin (Drug)

High Dose, Intramuscular

Active Comparator

Injection Capsaicin formulation higher dose - injected intramuscularly into trapezius

干预措施: Delsys Trigno Galileo System (Device)

High Dose, Intramuscular

Active Comparator

Injection Capsaicin formulation higher dose - injected intramuscularly into trapezius

干预措施: Sonosite Ultrasound Machine (Device)

High Dose, Intramuscular

Active Comparator

Injection Capsaicin formulation higher dose - injected intramuscularly into trapezius

干预措施: Goniometer (Device)

结局指标

主要结局

Motor Unit Action Potential Firing Rate

时间窗: up to 6 months

Firing rate will be determined using EMGworks software and compared with baseline firing rates.

Root Mean Square EMG values

时间窗: up to 6 months

Root mean square values will be compared with baseline values using EMGworks software.

Coefficient of Variation- Force steadiness

时间窗: up to 6 months

Force steadiness will be measured by the coefficient of variation (standard deviation/mean) using EMGworks software, validated through the goniometer measurements

Motor Unit Action Potential Amplitudes

时间窗: up to 6 months

Amplitudes will be measured from the overall amplitude difference from baseline for each motor unit using EMGworks software

Centroid of Frequency Spectrum

时间窗: up to 6 months

Centroid frequency will be measured and the frequency shift of the signal will be compared with baseline. Measured using EMGworks software

Texture Feature Analysis

时间窗: up to 6 months

91 features will be extracted using MATLAB, then a reduction of variables will be performed using principal component analysis. The experimental data will be compared with baseline results.

次要结局

  • Severity of pain(up to 6 months)

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Dinesh Kumbhare

Affiliate Scientist

Toronto Rehabilitation Institute

研究点 (1)

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