- ICH GCP
- Yhdysvaltain kliinisten tutkimusten rekisteri
- Kliininen tutkimus NCT07685509
Achilles Tendinopathy; the Effect of Shockwave Treatment
Comparison of Two Treatment Methods for Achilles Tendon Pain With a Focus on Pain, Function, Vascular Ingrowth, Immune Cell Response, and Cell Composition
BACKGROUND Achilles tendinopathy-pain in the Achilles tendon-is a common and often long-lasting condition that limits physical activity and performance, and also affects work capacity and quality of life. The pain is localized either to the mid- portion of the tendon or at its insertion into the calcaneus. Although individually tailored exercise is the first-line treatment, symptoms persist in many patients, highlighting the need for adjunctive therapies.
AIM This interdisciplinary and innovative research project aims to evaluate the effect of shockwave therapy in Achilles tendinopathy, both in cases where the pain is located in the mid-portion of the tendon and where it is situated at the tendon's insertion. In addition to assessing effects on pain and function, the study will examine the impact on calcifications, neovascularization (evaluated via Doppler ultrasound), and-uniquely-systemic immunological effects, with a focus on NK cells in the blood, an area that remains largely unexplored. METHOD This is a randomized controlled trial (RCT) with four arms, including 200 patients divided into two groups based on pain location. Half of the participants will receive adjunctive shockwave therapy in six sessions, in addition to exercise following the protocol by Silbernagel et al. The primary outcome measure is self-reported pain assessed using the Numeric Rating Scale (NRS) 0-10 at 12 months.
Secondary outcomes include function, assessed through patient-reported outcomes (Victorian Institute of Sport Assessment-Achilles Swedish version, VISA-AS), calf muscle strength and endurance, and jumping ability using a validated test battery. Neovascularization and tendon cross-sectional area will be evaluated using ultrasound/Doppler.
In a sub-cohort, immune cell composition in blood will be analyzed using flow cytometry before and after treatment. For patients undergoing surgery, tissue samples will also be collected for cellular composition analysis.
SIGNIFICANCE This project has the potential to improve treatment strategies, reduce the need for surgery, and generate entirely new knowledge about the relationship between local tissue pathology and systemic immune responses.
Tutkimuksen yleiskatsaus
Tila
Yksityiskohtainen kuvaus
Pain in the Achilles tendon, Achilles tendinopathy, is a common musculoskeletal condition affecting adults of all ages. The condition is characterized by localized pain and swelling in the Achilles tendon, particularly during tendon loading, functional limitations, and, in chronic cases, pathological neovascularization. Achilles tendinopathy is considered a typical overuse injury, and the diagnosis is made clinically. The incidence is reported to be 2/1000 per year, which would mean that approximately 1,400 individuals are affected each year in the Gothenburg area alone. A recent study from the United Kingdom has also shown that the typical patient is not physically active-as many clinical guidelines are designed for-but rather between 50 and 60 years old, has a high BMI, and often presents with comorbidities such as hypertension and diabetes. This highlights the need to review current clinical guidelines and evaluate the evidence for alternative treatments.
The pain is usually load-related and located either in the midportion of the Achilles tendon or at its insertion on the calcaneus. The condition is often long-lasting despite adequate treatment, and in addition to limiting physical activity, it can also affect work ability and quality of life. Non-operative treatment with heel-raise exercises and load management-appropriately dosed exercise-is the first-line standard, although long-standing or treatment-resistant cases may require adjunct therapies. Among these, extracorporeal shockwave therapy (ESWT), administered either radially (rESWT) or focally (fESWT), has emerged as a promising intervention in several studies, although it has been questioned in others. Shockwave therapy targets both pain relief and restoration of function, but its effects on pain, function, tendon morphology, and immune cell levels remain largely unexplored.
Recent systematic reviews have emphasized the need for higher-quality studies to determine whether adding shockwave therapy is beneficial for patients with Achilles tendinopathy. Evidence remains limited regarding whether shockwave therapy provides comparable pain relief for midportion versus insertional pain. Furthermore, it is unclear whether shockwave therapy must be combined with heel-raise exercises and load management or whether it can function as a standalone treatment.
Doppler ultrasound is commonly used to quantify neovascularization in the tendon. Some studies have shown that shockwave therapy induces transient increases in neovascularization that coincide with clinical improvement, while others have found no effect on neovascularization. Tendon thickness and the effect of shockwave therapy on intratendinous calcifications have also been investigated, but no consensus has been reached. Much of this research area remains unexplored due to the small number of studies and limited sample sizes.
Despite a growing evidence base suggesting that appropriately dosed exercise combined with shockwave therapy may be beneficial for tendon injuries, several areas remain under-investigated. Notably, no publications have been found on whether the micro-injuries potentially induced by shockwave therapy may cause systemic effects and thereby alter immune cell levels. Unpublished data from our research group have shown that early loading of a ruptured Achilles tendon increases circulating NK-cell levels, but whether this also applies to a painful tendon with potential tendinosis changes is unknown.
The aim of this project is to evaluate two different treatment methods for patients with Achilles tendinopathy-appropriately dosed exercise alone or appropriately dosed exercise combined with shockwave therapy-with a focus on:
Pain and muscle function
Neovascularization and calcifications in the tendon
Systemic changes in immune cell composition in the blood, with a focus on NK cells and CD8+ T cells
Hypotheses Appropriately dosed exercise combined with shockwave therapy leads to reduced pain and improved function compared with appropriately dosed exercise alone.
Appropriately dosed exercise combined with shockwave therapy reduces neovascularization and calcifications in the tendon.
Appropriately dosed exercise combined with shockwave therapy induces micro-injuries in the tendon that generate a systemic immune response (higher levels of NK cells and CD8+ T cells).
Appropriately dosed exercise combined with shockwave therapy has similar effects regardless of whether the pain is located in the midportion of the Achilles tendon or at its insertion.
Significance This project has the potential to improve the treatment of Achilles tendinopathy by identifying which patients benefit from shockwave therapy and by increasing the understanding of the biological effects of different treatment methods. The results may contribute to more individualized treatment and reduce the need for surgical interventions.
Opintotyyppi
Ilmoittautuminen (Arvioitu)
Vaihe
- Ei sovellettavissa
Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
- Aikuinen
- Vanhempi Aikuinen
Hyväksyy terveitä vapaaehtoisia
Kuvaus
Inclusion Criteria:
- Women and men over 18 years of age who seek care for load-related pain in the midportion of the Achilles tendon or at the Achilles tendon insertion at a Physiotherapy Clinic in Primary Care, at the Physiotherapy Department at Sahlgrenska University Hospital/Mölndal, or at the Orthopedic Department at Sahlgrenska University Hospital/Mölndal.
- Symptoms must have been present for one month or longer.
- Symptoms may be present in one or both Achilles tendons.
Exclusion Criteria:
- Unwillingness to receive shockwave therapy.
- Previous shockwave therapy for Achilles tendon pain within the past year.
- Neurological disease, significant cardiac conditions, increased bleeding tendency, treatment with anticoagulant medication, pregnancy, or presence of a tumor in the foot.
- Corticosteroid injection in the foot within the past six months.
- Reduced sensation, acute inflammation, or any wound around the heel.
- Inability to understand or speak Swedish.
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
|---|---|
|
Kokeellinen: Achilles Tendinopathy, exercise therapy and additional treatment with shockwave
Patients with Achilles Tendinopathy receiving exercise therapy with regular follow-ups and additional treatment with shockwave.
|
Shockwave: 5-6 treatments with radial shockwave, 10 bar, 2000-4000 pulses as an additional treatment to individually tailored exercises.
|
|
Active Comparator: Achilles Tendinopathy, exercise therapy
Patients with Achilles Tendinopathy receiving exercise therapy with regular follow-ups
|
Individually tailored exercises
|
|
Kokeellinen: Insertional Achilles Tendinopathy, exercise therapy and additional treatment with shockwave
Patients with Insertional Achilles Tendinopathy receiving exercise therapy with regular follow-ups and additional treatment with shockwave.
|
Shockwave: 5-6 treatments with radial shockwave, 10 bar, 2000-4000 pulses as an additional treatment to individually tailored exercises.
|
|
Active Comparator: Insertional Achilles Tendinopathy, exercise therapy
Patients with Insertional Achilles Tendinopathy receiving exercise therapy with regular follow-ups
|
Individually tailored exercises
|
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Change in self-reported pain from baseline to 12 months after treatment start
Aikaikkuna: At baseline and after 12 months after enrollment
|
Zero is equivalent to no pain and 10 indicates the worst possible pain.
|
At baseline and after 12 months after enrollment
|
Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Change in self-reported pain 3 and 6 months after treatment start
Aikaikkuna: At baseline and after 3 and 6 months after enrollment
|
Zero is equivalent to no pain and 10 indicates the worst possible pain.
|
At baseline and after 3 and 6 months after enrollment
|
|
Rate of blood vessels in the Achilles tendon
Aikaikkuna: At baseline and after 3, 6, and 12 month
|
Rate of blood vessels (n) (neovascularization) will be measured with Ultrasound in Doppler mode and compared with the healthy side.
|
At baseline and after 3, 6, and 12 month
|
|
Achilles Tendon cross-sectional area
Aikaikkuna: At baseline and after 3, 6 and 12 months
|
Achilles Tendon cross-sectional area in square centimeters will be evaluated with ultrasound in the midportion of the tendon
|
At baseline and after 3, 6 and 12 months
|
|
Physical Activity Scale (PAS)
Aikaikkuna: At baseline and after 3,6 and 12 months
|
A patient reported outcome used for the purpose to evaluate the patients self estimated physical activity level.
The scale is from 1 to 6 and the higher score, the better outcome.
|
At baseline and after 3,6 and 12 months
|
|
VISA-AS
Aikaikkuna: At baseline and after 3, 6 and 12 months
|
A valid and reliable questionnaire developed for patients with an Achilles Tendinopathy with a purpose to evaluate patient reported outcome in terms of symptoms and function.
The values can be between 0 and 100 and the higher score, the better outcome
|
At baseline and after 3, 6 and 12 months
|
|
Heel-rise height during heel-rise work test
Aikaikkuna: At baseline and after 3, 6 and 12 months
|
Evaluation of heel-rise height (cm) during heel-rise work test.
Comparison between groups in heel-rise height Limb Symmetry Index (LSI) - injured side/healthy side *100 expressed in percent.
The range in LSI is between 0-100% and the higher value, the better outcome
|
At baseline and after 3, 6 and 12 months
|
|
Evaluation of lower leg endurance with heel-rise work (Joule)
Aikaikkuna: At baseline and after 3, 6 and 12 months
|
Evaluation of lower leg endurance with heel-rise work (Joule) during heel-rise work test.
Comparison between groups in heel-rise work Limb Symmetry Index (LSI) - injured side/healthy side *100 expressed in percent.
The range in LSI is between 0-100% and the higher value, the better outcome
|
At baseline and after 3, 6 and 12 months
|
|
Numbers of heel-rises during heel-rise work test
Aikaikkuna: At baseline and after 3, 6 and 12 months
|
Evaluation of numbers of heel-rises during heel-rise work test.
Comparison between groups in numbers of heel-rises Limb Symmetry Index (LSI) - injured side/healthy side *100 expressed in percent.
The range in LSI is between 0-100% and the higher value, the better outcome
|
At baseline and after 3, 6 and 12 months
|
|
Calf muscle power
Aikaikkuna: At baseline and after 3, 6 and 12 months
|
Evaluation of calf muscle power in a weight training machine expressed in watt (Newton x meter /seconds).
Comparison will be performed between groups and limbs in power (LSI)- injured side/healthy side *100 expressed in percent.The range in LSI is between 0-100% and the higher value, the better outcome
|
At baseline and after 3, 6 and 12 months
|
|
Drop Countermovement Jump
Aikaikkuna: At baseline and after 3, 6 and 12 months
|
Drop Countermovement Jump: Evaluation of vertical jumping height after jumping from a 20 cm high box.
The outcome will be measured as the height the patient can perform in jump height after landing in cm.
Comparison between groups and limbs in jump height will be presented as Limb Symmetry Index (LSI)- injured side/healthy side *100 expressed in percent.
The range in LSI is between 0-100% and the higher value, the better outcome.
|
At baseline and after 3, 6 and 12 months
|
|
Hopping
Aikaikkuna: At baseline and after 3, 6 and 12 months
|
Evaluation of series of jumps as in jumping ropes.
The outcome measurement will be mean jumping height in cm and elasticity ratio in 20 jumps.
Comparison between groups and limbs in jump height and elasticity ratio will be presented as Limb Symmetry Index (LSI)- injured side/healthy side *100 expressed in percent.
The range in LSI is between 0-100% and the higher value, the better outcome
|
At baseline and after 3, 6 and 12 months
|
|
Range of motion in the ankle
Aikaikkuna: At baseline and after 3, 6 and 12 months
|
Range of motion in both ankles will be measured with an inclinometer in degrees both with the knee bent and with the knee straight.
Comparison between groups and limbs in jump height will be presented as Limb Symmetry Index (LSI)- injured side/healthy side *100 expressed in percent.
The range in LSI is between 0-100% and the higher value, the better outcome.
|
At baseline and after 3, 6 and 12 months
|
Muut tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Blood samples will be collected to assess changes in immune cell composition, focusing on NK and CD8+ T cells.
Aikaikkuna: At baseline and after 4-6 weeks
|
10 ml blood will be collected at two times from a cohort of the population.
Flow cytometry and antibody staining will be used for immune profiling.
|
At baseline and after 4-6 weeks
|
Yhteistyökumppanit ja tutkijat
Sponsori
Yhteistyökumppanit
Julkaisuja ja hyödyllisiä linkkejä
Yleiset julkaisut
- Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole MR. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001 Nov;94(2):149-158. doi: 10.1016/S0304-3959(01)00349-9.
- Alfredson H, Pietila T, Jonsson P, Lorentzon R. Heavy-load eccentric calf muscle training for the treatment of chronic Achilles tendinosis. Am J Sports Med. 1998 May-Jun;26(3):360-6. doi: 10.1177/03635465980260030301.
- Silbernagel KG, Gustavsson A, Thomee R, Karlsson J. Evaluation of lower leg function in patients with Achilles tendinopathy. Knee Surg Sports Traumatol Arthrosc. 2006 Nov;14(11):1207-17. doi: 10.1007/s00167-006-0150-6. Epub 2006 Jul 21.
- Silbernagel KG, Thomee R, Thomee P, Karlsson J. Eccentric overload training for patients with chronic Achilles tendon pain--a randomised controlled study with reliability testing of the evaluation methods. Scand J Med Sci Sports. 2001 Aug;11(4):197-206. doi: 10.1034/j.1600-0838.2001.110402.x.
- Rompe JD, Furia J, Maffulli N. Eccentric loading compared with shock wave treatment for chronic insertional achilles tendinopathy. A randomized, controlled trial. J Bone Joint Surg Am. 2008 Jan;90(1):52-61. doi: 10.2106/JBJS.F.01494.
- Cheng Y, Zhang J, Cai Y. Utility of Ultrasonography in Assessing the Effectiveness of Extracorporeal Shock Wave Therapy in Insertional Achilles Tendinopathy. Biomed Res Int. 2016;2016:2580969. doi: 10.1155/2016/2580969. Epub 2016 Nov 28.
- Santamato A, Beatrice R, Micello MF, Fortunato F, Panza F, Bristogiannis C, Cleopazzo E, Macarini L, Picelli A, Baricich A, Ranieri M. Power Doppler Ultrasound Findings before and after Focused Extracorporeal Shock Wave Therapy for Achilles Tendinopathy: A Pilot Study on Pain Reduction and Neovascularization Effect. Ultrasound Med Biol. 2019 May;45(5):1316-1323. doi: 10.1016/j.ultrasmedbio.2018.12.009. Epub 2019 Feb 8.
- Beyer R, Kongsgaard M, Hougs Kjaer B, Ohlenschlaeger T, Kjaer M, Magnusson SP. Heavy Slow Resistance Versus Eccentric Training as Treatment for Achilles Tendinopathy: A Randomized Controlled Trial. Am J Sports Med. 2015 Jul;43(7):1704-11. doi: 10.1177/0363546515584760. Epub 2015 May 27.
- Charles R, Fang L, Zhu R, Wang J. The effectiveness of shockwave therapy on patellar tendinopathy, Achilles tendinopathy, and plantar fasciitis: a systematic review and meta-analysis. Front Immunol. 2023 Aug 16;14:1193835. doi: 10.3389/fimmu.2023.1193835. eCollection 2023.
- de Jonge S, van den Berg C, de Vos RJ, van der Heide HJ, Weir A, Verhaar JA, Bierma-Zeinstra SM, Tol JL. Incidence of midportion Achilles tendinopathy in the general population. Br J Sports Med. 2011 Oct;45(13):1026-8. doi: 10.1136/bjsports-2011-090342.
- Silbernagel KG, Thomee R, Karlsson J. Cross-cultural adaptation of the VISA-A questionnaire, an index of clinical severity for patients with Achilles tendinopathy, with reliability, validity and structure evaluations. BMC Musculoskelet Disord. 2005 Mar 6;6:12. doi: 10.1186/1471-2474-6-12.
- Jonsson P, Alfredson H, Sunding K, Fahlstrom M, Cook J. New regimen for eccentric calf-muscle training in patients with chronic insertional Achilles tendinopathy: results of a pilot study. Br J Sports Med. 2008 Sep;42(9):746-9. doi: 10.1136/bjsm.2007.039545. Epub 2008 Jan 9.
- Gatz M, Schweda S, Betsch M, Dirrichs T, de la Fuente M, Reinhardt N, Quack V. Line- and Point-Focused Extracorporeal Shock Wave Therapy for Achilles Tendinopathy: A Placebo-Controlled RCT Study. Sports Health. 2021 Sep-Oct;13(5):511-518. doi: 10.1177/1941738121991791. Epub 2021 Feb 13.
- Feeney KM. The Effectiveness of Extracorporeal Shockwave Therapy for Midportion Achilles Tendinopathy: A Systematic Review. Cureus. 2022 Jul 18;14(7):e26960. doi: 10.7759/cureus.26960. eCollection 2022 Jul.
- Paantjens MA, Helmhout PH, Backx FJG, van Etten-Jamaludin FS, Bakker EWP. Extracorporeal Shockwave Therapy for Mid-portion and Insertional Achilles Tendinopathy: A Systematic Review of Randomized Controlled Trials. Sports Med Open. 2022 May 13;8(1):68. doi: 10.1186/s40798-022-00456-5.
- Stania M, Mala J, Chmielewska D. The Efficacy of Extracorporeal Shock Wave Therapy as a Monotherapy for Achilles Tendinopathy: A Systematic Review and Meta-Analysis. J Chiropr Med. 2023 Dec;22(4):294-301. doi: 10.1016/j.jcm.2023.04.003. Epub 2023 Jun 14.
- Pinitkwamdee S, Laohajaroensombat S, Orapin J, Woratanarat P. Effectiveness of Extracorporeal Shockwave Therapy in the Treatment of Chronic Insertional Achilles Tendinopathy. Foot Ankle Int. 2020 Apr;41(4):403-410. doi: 10.1177/1071100719898461. Epub 2020 Jan 10.
- Mansur NSB, Matsunaga FT, Carrazzone OL, Schiefer Dos Santos B, Nunes CG, Aoyama BT, Dias Dos Santos PR, Faloppa F, Tamaoki MJS. Shockwave Therapy Plus Eccentric Exercises Versus Isolated Eccentric Exercises for Achilles Insertional Tendinopathy: A Double-Blinded Randomized Clinical Trial. J Bone Joint Surg Am. 2021 Jul 21;103(14):1295-1302. doi: 10.2106/JBJS.20.01826.
- Butler JJ, DeClouette B, Azam MT, Walls RC, Jejelava G, Zheng D, Jia N, Kennedy JG. Outcomes After Extracorporeal Shockwave Therapy for Chronic Noninsertional Achilles Tendinopathy Compared With Chronic Insertional Achilles Tendinopathy: A Retrospective Review. Orthop J Sports Med. 2024 Sep 4;12(9):23259671241265330. doi: 10.1177/23259671241265330. eCollection 2024 Sep.
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- Rompe JD, Furia J, Maffulli N. Eccentric loading versus eccentric loading plus shock-wave treatment for midportion achilles tendinopathy: a randomized controlled trial. Am J Sports Med. 2009 Mar;37(3):463-70. doi: 10.1177/0363546508326983. Epub 2008 Dec 15.
- Verges J, Martinez N, Pascual A, Bibas M, Santina M, Rodas G. Psychosocial and individual factors affecting Quality of Life (QoL) in patients suffering from Achilles tendinopathy: a systematic review. BMC Musculoskelet Disord. 2022 Dec 21;23(1):1114. doi: 10.1186/s12891-022-06090-2.
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Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Arvioitu)
Ensisijainen valmistuminen (Arvioitu)
Opintojen valmistuminen (Arvioitu)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
Muut tutkimustunnusnumerot
- 2026-01721-01 (Muu tunniste: The Swedish Ethical Review Authority)
- P2026-0030 (Muu apuraha/rahoitusnumero: Swedish Research Council for Sport Science)
Yksittäisten osallistujien tietojen suunnitelma (IPD)
Aiotko jakaa yksittäisten osallistujien tietoja (IPD)?
Lääke- ja laitetiedot, tutkimusasiakirjat
Tutkii yhdysvaltalaista FDA sääntelemää lääkevalmistetta
Tutkii yhdysvaltalaista FDA sääntelemää laitetuotetta
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