Quantitative Ultrasound Response of Capsaicin

NCT03944889 | Completed Early Phase 1 FDA Drug FDA Device

• 1 other identifier: CapsaicinUltrasound
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Central Sensitisation

Keywords

MUAP- Motor Unit Action Potential; RMS- Root Mean Square; US-Ultrasound

Outcome Measures

Primary Outcomes (6)

• Motor Unit Action Potential Firing Rate

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

  up to 6 months

• Root Mean Square EMG values

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

  up to 6 months

• Coefficient of Variation- Force steadiness

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

  up to 6 months

• Motor Unit Action Potential Amplitudes

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

  up to 6 months

• Centroid of Frequency Spectrum

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

  up to 6 months

• Texture Feature Analysis

  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.

  up to 6 months

Secondary Outcomes (1)

• Severity of pain

  up to 6 months

Study Arms (9)

Placebo Topical

PLACEBO COMPARATOR

Placebo Cream, applied topically to trapezius muscle

Device: Delsys Trigno Galileo System; Device: Cadwell Sierra Wave; Device: Sonosite Ultrasound Machine; Device: Goniometer

Low Dose, Topical

ACTIVE COMPARATOR

Capsaicin Cream- low dosage, applied topically to trapezius

Drug: Capsaicin; Device: Delsys Trigno Galileo System; Device: Cadwell Sierra Wave; Device: Sonosite Ultrasound Machine; Device: Goniometer

High Dose, Topical

ACTIVE COMPARATOR

Capsaicin Cream- higher dosage, applied topically to trapezius

Drug: Capsaicin; Device: Delsys Trigno Galileo System; Device: Cadwell Sierra Wave; Device: Sonosite Ultrasound Machine; Device: Goniometer

Placebo, Intrafascial

PLACEBO COMPARATOR

Injection placebo(saline)- injected intrafascially into trapezius

Device: Delsys Trigno Galileo System; Device: Cadwell Sierra Wave; Device: Sonosite Ultrasound Machine; Device: Goniometer

Low Dose, Intrafacial

ACTIVE COMPARATOR

Injection Capsaicin formulation low dose- injected intrafascially into trapezius

Drug: Capsaicin; Device: Delsys Trigno Galileo System; Device: Cadwell Sierra Wave; Device: Sonosite Ultrasound Machine; Device: Goniometer

High Dose, Intrafascial

ACTIVE COMPARATOR

Injection Capsaicin formulation higher dose- injected intrafascially into trapezius

Drug: Capsaicin; Device: Delsys Trigno Galileo System; Device: Cadwell Sierra Wave; Device: Sonosite Ultrasound Machine; Device: Goniometer

Placebo, Intramuscular

PLACEBO COMPARATOR

Injection placebo (saline) - injected intramuscularly into trapezius

Device: Delsys Trigno Galileo System; Device: Cadwell Sierra Wave; Device: Sonosite Ultrasound Machine; Device: Goniometer

Low Dose, Intramuscular

ACTIVE COMPARATOR

Injection Capsaicin formulation low dose - injected intramuscularly into trapezius

Drug: Capsaicin; Device: Delsys Trigno Galileo System; Device: Cadwell Sierra Wave; Device: Sonosite Ultrasound Machine; Device: Goniometer

High Dose, Intramuscular

ACTIVE COMPARATOR

Injection Capsaicin formulation higher dose - injected intramuscularly into trapezius

Drug: Capsaicin; Device: Delsys Trigno Galileo System; Device: Cadwell Sierra Wave; Device: Sonosite Ultrasound Machine; Device: Goniometer

Interventions

Capsaicin DRUG

Capsaicin 50ug (low dose), Capsaicin 100ug(high dose) will be administered as a topical skin cream and will be intermixed with saline for the injectable solution.

High Dose, Intrafascial; High Dose, Intramuscular; High Dose, Topical; Low Dose, Intrafacial; Low Dose, Intramuscular; Low Dose, Topical

Delsys Trigno Galileo System DEVICE

This device is a wireless surface EMG device.

High Dose, Intrafascial; High Dose, Intramuscular; High Dose, Topical; Low Dose, Intrafacial; Low Dose, Intramuscular; Low Dose, Topical; Placebo Topical; Placebo, Intrafascial; Placebo, Intramuscular

Cadwell Sierra Wave DEVICE

Intramuscular EMG recording machinery

High Dose, Intrafascial; High Dose, Intramuscular; High Dose, Topical; Low Dose, Intrafacial; Low Dose, Intramuscular; Low Dose, Topical; Placebo Topical; Placebo, Intrafascial; Placebo, Intramuscular

Sonosite Ultrasound Machine DEVICE

Ultrasound System

High Dose, Intrafascial; High Dose, Intramuscular; High Dose, Topical; Low Dose, Intrafacial; Low Dose, Intramuscular; Low Dose, Topical; Placebo Topical; Placebo, Intrafascial; Placebo, Intramuscular

Goniometer DEVICE

A device to measure angular position

High Dose, Intrafascial; High Dose, Intramuscular; High Dose, Topical; Low Dose, Intrafacial; Low Dose, Intramuscular; Low Dose, Topical; Placebo Topical; Placebo, Intrafascial; Placebo, Intramuscular

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Toronto Rehabilitation Institute: lead

Study Sites (1)

Toronto Rehabilitation Institute

Toronto, Ontario, M5S 1A1, Canada

Location

Related Publications (45)

• Srbely JZ. New trends in the treatment and management of myofascial pain syndrome. Curr Pain Headache Rep. 2010 Oct;14(5):346-52. doi: 10.1007/s11916-010-0128-4.

  PMID: 20607458 BACKGROUND

• Masuda T, Sadoyama T. Distribution of innervation zones in the human biceps brachii. J Electromyogr Kinesiol. 1991 Jun;1(2):107-15. doi: 10.1016/1050-6411(91)90004-O.

  PMID: 20870500 BACKGROUND

• Barbero M, Cescon C, Tettamanti A, Leggero V, Macmillan F, Coutts F, Gatti R. Myofascial trigger points and innervation zone locations in upper trapezius muscles. BMC Musculoskelet Disord. 2013 Jun 8;14:179. doi: 10.1186/1471-2474-14-179.

  PMID: 23758854 BACKGROUND

• Melzack R, Stillwell DM, Fox EJ. Trigger points and acupuncture points for pain: correlations and implications. Pain. 1977 Feb;3(1):3-23. doi: 10.1016/0304-3959(77)90032-X.

  PMID: 69288 BACKGROUND

• Hong CZ, Simons DG. Pathophysiologic and electrophysiologic mechanisms of myofascial trigger points. Arch Phys Med Rehabil. 1998 Jul;79(7):863-72. doi: 10.1016/s0003-9993(98)90371-9.

  PMID: 9685106 BACKGROUND

• Gerwin RD, Dommerholt J, Shah JP. An expansion of Simons' integrated hypothesis of trigger point formation. Curr Pain Headache Rep. 2004 Dec;8(6):468-75. doi: 10.1007/s11916-004-0069-x.

  PMID: 15509461 BACKGROUND

• Bron C, Dommerholt JD. Etiology of myofascial trigger points. Curr Pain Headache Rep. 2012 Oct;16(5):439-44. doi: 10.1007/s11916-012-0289-4.

  PMID: 22836591 BACKGROUND

• Yu SH, Kim HJ. Electrophysiological characteristics according to activity level of myofascial trigger points. J Phys Ther Sci. 2015 Sep;27(9):2841-3. doi: 10.1589/jpts.27.2841. Epub 2015 Sep 30.

  PMID: 26504306 BACKGROUND

• Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011 Mar;152(3 Suppl):S2-S15. doi: 10.1016/j.pain.2010.09.030. Epub 2010 Oct 18.

  PMID: 20961685 BACKGROUND

• Graven-Nielsen T, Arendt-Nielsen L. Assessment of mechanisms in localized and widespread musculoskeletal pain. Nat Rev Rheumatol. 2010 Oct;6(10):599-606. doi: 10.1038/nrrheum.2010.107. Epub 2010 Jul 27.

  PMID: 20664523 BACKGROUND

• Fernandez-de-las-Penas C, Cuadrado ML, Arendt-Nielsen L, Simons DG, Pareja JA. Myofascial trigger points and sensitization: an updated pain model for tension-type headache. Cephalalgia. 2007 May;27(5):383-93. doi: 10.1111/j.1468-2982.2007.01295.x. Epub 2007 Mar 14.

  PMID: 17359516 BACKGROUND

• Kim Y, Kim J, Shim JK, Suh DW, Yoon B. The hypoalgesic effect of remote tactile sensory modulation on the mechanical sensitivity of trigger points: A randomized controlled study. NeuroRehabilitation. 2014;35(3):607-14. doi: 10.3233/NRE-141156.

  PMID: 25248449 BACKGROUND

• LaMotte RH, Lundberg LE, Torebjork HE. Pain, hyperalgesia and activity in nociceptive C units in humans after intradermal injection of capsaicin. J Physiol. 1992 Mar;448:749-64. doi: 10.1113/jphysiol.1992.sp019068.

  PMID: 1593488 BACKGROUND

• Srbely JZ, Dickey JP, Bent LR, Lee D, Lowerison M. Capsaicin-induced central sensitization evokes segmental increases in trigger point sensitivity in humans. J Pain. 2010 Jul;11(7):636-43. doi: 10.1016/j.jpain.2009.10.005. Epub 2009 Dec 16.

  PMID: 20015704 BACKGROUND

• Torebjork HE, Lundberg LE, LaMotte RH. Central changes in processing of mechanoreceptive input in capsaicin-induced secondary hyperalgesia in humans. J Physiol. 1992 Mar;448:765-80. doi: 10.1113/jphysiol.1992.sp019069.

  PMID: 1593489 BACKGROUND

• Dideriksen JL, Holobar A, Falla D. Preferential distribution of nociceptive input to motoneurons with muscle units in the cranial portion of the upper trapezius muscle. J Neurophysiol. 2016 Aug 1;116(2):611-8. doi: 10.1152/jn.01117.2015. Epub 2016 May 25.

  PMID: 27226455 BACKGROUND

• Falla D, Farina D. Motor units in cranial and caudal regions of the upper trapezius muscle have different discharge rates during brief static contractions. Acta Physiol (Oxf). 2008 Apr;192(4):551-8. doi: 10.1111/j.1748-1716.2007.01776.x. Epub 2007 Nov 2.

  PMID: 17979997 BACKGROUND

• Lee U, Kim M, Lee K, Kaplan CM, Clauw DJ, Kim S, Mashour GA, Harris RE. Functional Brain Network Mechanism of Hypersensitivity in Chronic Pain. Sci Rep. 2018 Jan 10;8(1):243. doi: 10.1038/s41598-017-18657-4.

  PMID: 29321621 BACKGROUND

• Schmidt-Wilcke T, Clauw DJ. Fibromyalgia: from pathophysiology to therapy. Nat Rev Rheumatol. 2011 Jul 19;7(9):518-27. doi: 10.1038/nrrheum.2011.98.

  PMID: 21769128 BACKGROUND

• HENNEMAN E, SOMJEN G, CARPENTER DO. FUNCTIONAL SIGNIFICANCE OF CELL SIZE IN SPINAL MOTONEURONS. J Neurophysiol. 1965 May;28:560-80. doi: 10.1152/jn.1965.28.3.560. No abstract available.

  PMID: 14328454 BACKGROUND

• Ertas M, Stalberg E, Falck B. Can the size principle be detected in conventional EMG recordings? Muscle Nerve. 1995 Apr;18(4):435-9. doi: 10.1002/mus.880180410.

  PMID: 7715629 BACKGROUND

• Vilensky JA, Gilman S. Renaming the "Henneman size principle". Science. 1998 Jun 26;280(5372):2031. doi: 10.1126/science.280.5372.2027f. No abstract available.

  PMID: 9669955 BACKGROUND

• Szolcsanyi J. A pharmacological approach to elucidation of the role of different nerve fibres and receptor endings in mediation of pain. J Physiol (Paris). 1977 Sep;73(3):251-9.

  PMID: 926026 BACKGROUND

• Carpenter SE, Lynn B. Vascular and sensory responses of human skin to mild injury after topical treatment with capsaicin. Br J Pharmacol. 1981 Jul;73(3):755-8. doi: 10.1111/j.1476-5381.1981.tb16812.x.

  PMID: 6166346 BACKGROUND

• Simone DA, Baumann TK, LaMotte RH. Dose-dependent pain and mechanical hyperalgesia in humans after intradermal injection of capsaicin. Pain. 1989 Jul;38(1):99-107. doi: 10.1016/0304-3959(89)90079-1.

  PMID: 2780068 BACKGROUND

• Ishimaru K, Kawakita K, Sakita M. Analgesic effects induced by TENS and electroacupuncture with different types of stimulating electrodes on deep tissues in human subjects. Pain. 1995 Nov;63(2):181-187. doi: 10.1016/0304-3959(95)00030-V.

  PMID: 8628583 BACKGROUND

• Langevin HM, Fox JR, Koptiuch C, Badger GJ, Greenan-Naumann AC, Bouffard NA, Konofagou EE, Lee WN, Triano JJ, Henry SM. Reduced thoracolumbar fascia shear strain in human chronic low back pain. BMC Musculoskelet Disord. 2011 Sep 19;12:203. doi: 10.1186/1471-2474-12-203.

  PMID: 21929806 BACKGROUND

• Schilder A, Hoheisel U, Magerl W, Benrath J, Klein T, Treede RD. Sensory findings after stimulation of the thoracolumbar fascia with hypertonic saline suggest its contribution to low back pain. Pain. 2014 Feb;155(2):222-231. doi: 10.1016/j.pain.2013.09.025. Epub 2013 Sep 26.

  PMID: 24076047 BACKGROUND

• Barbero M, Gatti R, Lo Conte L, Macmillan F, Coutts F, Merletti R. Reliability of surface EMG matrix in locating the innervation zone of upper trapezius muscle. J Electromyogr Kinesiol. 2011 Oct;21(5):827-33. doi: 10.1016/j.jelekin.2011.05.013. Epub 2011 Jul 12.

  PMID: 21752668 BACKGROUND

• Kumbhare D, Shaw S, Grosman-Rimon L, Noseworthy MD. Quantitative Ultrasound Assessment of Myofascial Pain Syndrome Affecting the Trapezius: A Reliability Study. J Ultrasound Med. 2017 Dec;36(12):2559-2568. doi: 10.1002/jum.14308. Epub 2017 Jul 3.

  PMID: 28670779 BACKGROUND

• Kumbhare DA, Ahmed S, Behr MG, Noseworthy MD. Quantitative Ultrasound Using Texture Analysis of Myofascial Pain Syndrome in the Trapezius. Crit Rev Biomed Eng. 2018;46(1):1-31. doi: 10.1615/CritRevBiomedEng.2017024947.

  PMID: 29717675 BACKGROUND

• Farina D, Madeleine P, Graven-Nielsen T, Merletti R, Arendt-Nielsen L. Standardising surface electromyogram recordings for assessment of activity and fatigue in the human upper trapezius muscle. Eur J Appl Physiol. 2002 Apr;86(6):469-78. doi: 10.1007/s00421-001-0574-0. Epub 2002 Feb 19.

  PMID: 11944093 BACKGROUND

• Holobar A, Zazula D. Correlation-based decomposition of surface electromyograms at low contraction forces. Med Biol Eng Comput. 2004 Jul;42(4):487-95. doi: 10.1007/BF02350989.

  PMID: 15320457 BACKGROUND

• Holobar A, Zazula D. Multichannel blind source separation using convolution kernel compensation. IEEE Transactions on Signal Processing 2007;55(9):4487-96.

  BACKGROUND

• Henneman E, Mendell LM. Functional organization of motoneuron pool and its inputs. Handbook of Physiology. The Nervous System. Motor Control. 1981;1:423-507

  BACKGROUND

• Holobar A, Farina D, Gazzoni M, Merletti R, Zazula D. Estimating motor unit discharge patterns from high-density surface electromyogram. Clin Neurophysiol. 2009 Mar;120(3):551-62. doi: 10.1016/j.clinph.2008.10.160. Epub 2009 Feb 8.

  PMID: 19208498 BACKGROUND

• Holobar A, Minetto MA, Botter A, Negro F, Farina D. Experimental analysis of accuracy in the identification of motor unit spike trains from high-density surface EMG. IEEE Trans Neural Syst Rehabil Eng. 2010 Jun;18(3):221-9. doi: 10.1109/TNSRE.2010.2041593. Epub 2010 Feb 8.

  PMID: 20144921 BACKGROUND

• Holobar A, Glaser V, Gallego JA, Dideriksen JL, Farina D. Non-invasive characterization of motor unit behaviour in pathological tremor. J Neural Eng. 2012 Oct;9(5):056011. doi: 10.1088/1741-2560/9/5/056011. Epub 2012 Sep 10.

  PMID: 22962251 BACKGROUND

• Bandholm T, Rasmussen L, Aagaard P, Diederichsen L, Jensen BR. Effects of experimental muscle pain on shoulder-abduction force steadiness and muscle activity in healthy subjects. Eur J Appl Physiol. 2008 Apr;102(6):643-50. doi: 10.1007/s00421-007-0642-1. Epub 2007 Dec 8.

  PMID: 18066578 BACKGROUND

• Huynh H, Feldt LS. Estimation of the Box correction for degrees of freedom from sample data in randomized block and split-plot designs. J Edu Stat 1976;1(1):69-82

  BACKGROUND

• Shah JP, Gilliams EA. Uncovering the biochemical milieu of myofascial trigger points using in vivo microdialysis: an application of muscle pain concepts to myofascial pain syndrome. J Bodyw Mov Ther. 2008 Oct;12(4):371-384. doi: 10.1016/j.jbmt.2008.06.006. Epub 2008 Aug 13.

  PMID: 19083696 BACKGROUND

• Falla D, Farina D, Graven-Nielsen T. Experimental muscle pain results in reorganization of coordination among trapezius muscle subdivisions during repetitive shoulder flexion. Exp Brain Res. 2007 Apr;178(3):385-93. doi: 10.1007/s00221-006-0746-6. Epub 2006 Oct 19.

  PMID: 17051373 BACKGROUND

• Mclean L, Urquhart N. The influence of psychological stressors on myoelectrical signal activity in the shoulder region during a data entry task. Work Stress 2002;16(2):138-53

  BACKGROUND

• Westad C. Motor control of the upper trapezius. 2005

  BACKGROUND

• Evans V, Behr M, Masani K, Kumbhare D. Quantitative response of healthy muscle following the induction of capsaicin: an exploratory randomized controlled trial. Trials. 2020 Dec 11;21(1):1020. doi: 10.1186/s13063-020-04937-4.

  PMID: 33308274 DERIVED

MeSH Terms

Interventions

Capsaicin

Intervention Hierarchy (Ancestors)

Polyunsaturated Alkamides; Amides; Organic Chemicals; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Fatty Acids; Lipids

Study Officials

• Dinesh M Kumbahre, MD,PhD

  Toronto Rehabilitation Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Affiliate Scientist

Model Details: A single-centered, factorial, randomized, placebo-controlled trial with two independent variables (dosage and depth of application).

Study Record Dates

• First Submitted: May 3, 2019
• First Posted: May 10, 2019
• Study Start: July 1, 2019
• Primary Completion: July 1, 2020
• Study Completion: December 1, 2020
• Last Updated: December 3, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)