Optimal Treatment of Acute Skeletal Muscle Injury

NCT06274151 | Not Yet Recruiting DMC

• 1 other identifier: H-22038917
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

Acute muscle strain injuries occur both during sports, in leisure time activities and during manual occupation and represent a major clinical challenge and has societal economic costs. The recovery time is long and a substantial injury recurrence is observed. Despite current best evidence rehabilitation with early mechanical loading, a significant loss of muscle mass, fatty infiltration and formation of scar tissue is reported. Animal models and human in vitro experiments suggest that inflammation is vital in the early period after an injury, however an inhibition of inflammatory processes is beneficial for healing. We investigate here whether a pharmacological inhibition of inflammatory pathways in the 2nd week following a muscle strain injury will provide a better clinical outcome and an advantageous cellular profile than rehabilitative training alone would.

Conditions

Muscle Strain, Multiple Sites; Inflammation

Outcome Measures

Primary Outcomes (1)

• Effect of anti-inflammatory medicine on cellular profile in skeletal muscle

  Single-nuclei RNA sequencing (seq) of muscle tissue after a strain injury. Single nuclei RNA seq will be performed on biopsies obtained in week 1 after the strain injury. The cellular profile will be compared to the contralateral healthy muscle. Another biopsy, in both the injured and contralateral healthy muscle will be taken in week 3 post injury to investigate the effect of one week of Naproxen treatment versus inert placebo pills on the cellular profile measured with single nuclei RNA seq.

  12 months

Secondary Outcomes (3)

• Functional outcome performance

  Up to 12 months

• Functional outcome re-injury rate

  12 months

• Functional outcome Patient Related Outcome Measures (PROM)

  12 months

Study Arms (2)

Anti-inflammatory medicine

EXPERIMENTAL

Week 2 after muscle strain injury Naproxen 500mg 2x daily

Drug: Naproxen 500 Mg; Procedure: Rehabilitation

Placebo

PLACEBO COMPARATOR

Week 2 after muscle strain injury Placebo pill, no active compounds 2x daily

Procedure: Rehabilitation; Drug: Placebo

Interventions

Naproxen 500 Mg DRUG

Attenuating the sub-acute inflammatory processes to monitor potential beneficial tissue healing following a muscle strain injury

Also known as: Anti-inflammatory Agents, Non-steroidal

Anti-inflammatory medicine

Rehabilitation PROCEDURE

Rehabilitation after muscle strain injury

Also known as: Physical therapy to stimulate tissue healing

Anti-inflammatory medicine; Placebo

Placebo DRUG

Sub-acute inflammatory processes not attenuated. Group will be treated as control to monitor tissue healing following a muscle strain injury without pharmacological intervention.

Also known as: inert pills

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sports-active individuals with an acute muscle train injury in either the hamstrings or calf muscle caused by an explosive movement (during sprinting, jumping etc)
• Age older than 18 years

You may not qualify if:

• Lack of hypoechoic/ hyperechoic area on ultrasound
• Diabetes type I and II
• Connective tissue disorders, rheumatism or any other chronic disease affecting the musculoskeletal system
• Anticoagulant medication
• Needle phobia

Sponsors & Collaborators

• Bispebjerg Hospital: lead

Related Publications (11)

• Ekstrand J, Hagglund M, Walden M. Injury incidence and injury patterns in professional football: the UEFA injury study. Br J Sports Med. 2011 Jun;45(7):553-8. doi: 10.1136/bjsm.2009.060582. Epub 2009 Jun 23.

  PMID: 19553225 BACKGROUND

• Wangensteen A, Tol JL, Witvrouw E, Van Linschoten R, Almusa E, Hamilton B, Bahr R. Hamstring Reinjuries Occur at the Same Location and Early After Return to Sport: A Descriptive Study of MRI-Confirmed Reinjuries. Am J Sports Med. 2016 Aug;44(8):2112-21. doi: 10.1177/0363546516646086. Epub 2016 May 16.

  PMID: 27184543 BACKGROUND

• Chazaud B. Inflammation during skeletal muscle regeneration and tissue remodeling: application to exercise-induced muscle damage management. Immunol Cell Biol. 2016 Feb;94(2):140-5. doi: 10.1038/icb.2015.97. Epub 2015 Nov 3.

  PMID: 26526620 BACKGROUND

• Saclier M, Yacoub-Youssef H, Mackey AL, Arnold L, Ardjoune H, Magnan M, Sailhan F, Chelly J, Pavlath GK, Mounier R, Kjaer M, Chazaud B. Differentially activated macrophages orchestrate myogenic precursor cell fate during human skeletal muscle regeneration. Stem Cells. 2013 Feb;31(2):384-96. doi: 10.1002/stem.1288.

  PMID: 23169615 BACKGROUND

• Wynn TA, Vannella KM. Macrophages in Tissue Repair, Regeneration, and Fibrosis. Immunity. 2016 Mar 15;44(3):450-462. doi: 10.1016/j.immuni.2016.02.015.

  PMID: 26982353 BACKGROUND

• Bayer ML, Hoegberget-Kalisz M, Svensson RB, Hjortshoej MH, Olesen JL, Nybing JD, Boesen M, Magnusson SP, Kjaer M. Chronic Sequelae After Muscle Strain Injuries: Influence of Heavy Resistance Training on Functional and Structural Characteristics in a Randomized Controlled Trial. Am J Sports Med. 2021 Aug;49(10):2783-2794. doi: 10.1177/03635465211026623. Epub 2021 Jul 15.

  PMID: 34264782 BACKGROUND

• Bayer ML, Magnusson SP, Kjaer M; Tendon Research Group Bispebjerg. Early versus Delayed Rehabilitation after Acute Muscle Injury. N Engl J Med. 2017 Sep 28;377(13):1300-1301. doi: 10.1056/NEJMc1708134. No abstract available.

  PMID: 28953439 BACKGROUND

• Bayer ML, Hoegberget-Kalisz M, Jensen MH, Olesen JL, Svensson RB, Couppe C, Boesen M, Nybing JD, Kurt EY, Magnusson SP, Kjaer M. Role of tissue perfusion, muscle strength recovery, and pain in rehabilitation after acute muscle strain injury: A randomized controlled trial comparing early and delayed rehabilitation. Scand J Med Sci Sports. 2018 Dec;28(12):2579-2591. doi: 10.1111/sms.13269. Epub 2018 Aug 16.

  PMID: 30043997 BACKGROUND

• Silder A, Sherry MA, Sanfilippo J, Tuite MJ, Hetzel SJ, Heiderscheit BC. Clinical and morphological changes following 2 rehabilitation programs for acute hamstring strain injuries: a randomized clinical trial. J Orthop Sports Phys Ther. 2013 May;43(5):284-99. doi: 10.2519/jospt.2013.4452. Epub 2013 Mar 13.

  PMID: 23485730 BACKGROUND

• Cohen S, Nathan JA, Goldberg AL. Muscle wasting in disease: molecular mechanisms and promising therapies. Nat Rev Drug Discov. 2015 Jan;14(1):58-74. doi: 10.1038/nrd4467.

  PMID: 25549588 BACKGROUND

• Bayer ML, Bang L, Hoegberget-Kalisz M, Svensson RB, Olesen JL, Karlsson MM, Schjerling P, Hellsten Y, Hoier B, Magnusson SP, Kjaer M. Muscle-strain injury exudate favors acute tissue healing and prolonged connective tissue formation in humans. FASEB J. 2019 Sep;33(9):10369-10382. doi: 10.1096/fj.201900542R. Epub 2019 Jun 18.

  PMID: 31211922 BACKGROUND

MeSH Terms

Conditions

Sprains and Strains; Inflammation

Interventions

Naproxen; Anti-Inflammatory Agents, Non-Steroidal; Rehabilitation

Condition Hierarchy (Ancestors)

Wounds and Injuries; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Anti-Inflammatory Agents; Therapeutic Uses; Antirheumatic Agents; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Michael L Kjaer, DMSCi

  Bispebjerg Hospital

  STUDY DIRECTOR

Central Study Contacts

Monika Lucia L Bayer, PhD

CONTACT

+4525687931; monika.lucia.bayer@regionh.dk

Simon E Jespersen, MD

CONTACT

Simon.Elmer.jespersen@regionh.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Researcher

Study Record Dates

• First Submitted: January 30, 2024
• First Posted: February 23, 2024
• Study Start: February 15, 2024
• Primary Completion: July 31, 2025
• Study Completion (Estimated): December 31, 2029
• Last Updated: February 23, 2024

Record last verified: 2024-01