Acute Cryotherapy on Musculoskeletal Function and Biomarkers

NCT07211412 | Not Yet Recruiting

• 1 other identifier: 2356825
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

In 2020, Dubois and Esculier proposed a paradigm shift in the acute management of musculoskeletal injuries, advocating for the transition from the traditional PRICE protocol- Protect, Rest, Ice, Compression, Elevation-to the more holistic PEACE \& LOVE framework. This updated model emphasizes Protection, Elevation, Avoiding anti-inflammatories, Compression, and Education, followed by Load, Optimism, Vascularization, and Exercise. Notably, the PEACE \& LOVE approach omits the use of ice, a decision that has sparked considerable debate. While the rationale centers on avoiding interference with the natural inflammatory and regenerative processes, this omission stands in contrast to a substantial body of animal research suggesting that cryotherapy can mitigate secondary tissue injury by reducing inflammation and metabolic activity. Despite its widespread clinical use, human studies have yet to provide conclusive evidence supporting or refuting the efficacy of cryotherapy in acute injury management, leaving clinicians to navigate between tradition, emerging evidence, and evolving philosophies of care. Even though it is important to consider natural inflammation for a better regenerative process, animal models have shown that the original injury can elicit oxidative stress, which will enhance cellular damage (secondary damage) and inflammation. Clinically, it is unknown if this secondary damage would increase functional impairment. Therefore, this proposal will determine if cryotherapy can decrease secondary damage, after exercise-induced muscle damage, and if this decrease is associated to lower inflammation, oxidative stress and functional impairments.

Conditions

Exercise Induced Muscle Damage; Cryotherapy

Keywords

Exercise induced muscle damage; Cryotherapy; Cold-pack; Ice-pack; Eccentric exercise; Creatine kinase; c-reactive protein; interlukin-6; 8-isoprostane; Range of motion; Maximal Voluntary Isometric Contraction; Pain

Outcome Measures

Primary Outcomes (5)

• Maximal Voluntary Isometric Contraction (MVIC)

  Laid down on an isokinetic dynamometer system (Humac-Norm, Computer Sports Medicine, inc., Stoughton, MA), participants will be asked to flex their non-dominant arm (pull with their hand) against the dynamometer. They will perform 3 tries with 1 minute between tries and the peak value will be considered the MVIC.

  From enrollment to the end of study at 12 days

• Peak Pressure Threshold (PPT)

  PPT is the application of an algometer, which measure pressure on a specific body point (see figure below), while asking the participant 2 questions: 1) tell me when the pressure becomes pain and 2) how much pain you felt from 0 to 100, where 0 is no pain and 100 is the larger pain you have ever experienced. PPT will be performed over the flexor muscles (biceps brachialis) of the non-dominant arm.

  From enrollment to the end of study at 12 days.

• Creatine kinase

  Blood biomarker of muscle damage. Blood draws will be performed before and 0, 24, 48, 72, and 96 hours after EIMD.

  From enrollment to the end of treatment at 5 days

• Interleukin-6

  Blood biomarker of inflammation. Blood draws will be performed before and 0, 24, 48, 72, and 96 hours after EIMD.

  From enrollment to the end of treatment at 5 days

• 8-isoprostane

  Blood biomarker of oxidative stress. Blood draws will be performed before and 0, 24, 48, 72, and 96 hours after EIMD.

  From enrollment to the end of treatment at 5 days

Secondary Outcomes (3)

• Arm girth

  From enrollment to the end of study at 12 days.

• Active Range of Motion (ROM)

  From enrollment to the end of study at 12 days.

• C-reactive protein

  From enrollment to the end of treatment at 5 days.

Study Arms (3)

Control-control

NO INTERVENTION

This arm will include no intervention and only functional assessments and blood draws for biomarkers.

Control

PLACEBO COMPARATOR

This arm will have eccentric exercise-induced muscle damage on day 0 and then 15-min of room temperature cold-pack immediately after and then for 4 more days every 24 hours.

Other: Eccentric exercise-induced muscle damage

Cryotherapy

ACTIVE COMPARATOR

This arm will have eccentric exercise-induced muscle damage on day 0 and then 15-min of cold (-5°C) cold-pack immediately after and then for 4 more days every 24 hours.

Other: Cryotherapy; Other: Eccentric exercise-induced muscle damage

Interventions

Cryotherapy OTHER

A cold (-5°C) cold-pack for 15 minutes every 24 hours for 5 days

Also known as: cold-pack, ice-pack

Cryotherapy

Eccentric exercise-induced muscle damage OTHER

3 sets of 15 repetitions of eccentric contractions at 80% of 1RM. This is to induced a controlled muscle damage in 2 of the 3 arms.

Also known as: doms

Control; Cryotherapy

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• apparently healthy
• normotensive
• non-smokers (all tobacco products including e-cigarettes)

You may not qualify if:

• Cardiovascular diseases (including hypertension)
• pregnancy
• any musculoskeletal injury 6 months prior the study

Sponsors & Collaborators

• University of Texas, El Paso: lead

Study Sites (1)

The University of Texas at El Paso, Rehabilitation Sciences Complex

El Paso, Texas, 79968, United States

Location

Related Publications (9)

• Qu C, Wu Z, Xu M, Qin F, Dong Y, Wang Z, Zhao J. Cryotherapy Models and Timing-Sequence Recovery of Exercise-Induced Muscle Damage in Middle- and Long-Distance Runners. J Athl Train. 2020 Apr;55(4):329-335. doi: 10.4085/1062-6050-529-18. Epub 2020 Mar 11.

  PMID: 32160058 BACKGROUND

• Pooley S, Spendiff O, Allen M, Moir HJ. Comparative efficacy of active recovery and cold water immersion as post-match recovery interventions in elite youth soccer. J Sports Sci. 2020 Jun-Jun;38(11-12):1423-1431. doi: 10.1080/02640414.2019.1660448. Epub 2019 Aug 28.

  PMID: 31456474 BACKGROUND

• Rose C, Edwards KM, Siegler J, Graham K, Caillaud C. Whole-body Cryotherapy as a Recovery Technique after Exercise: A Review of the Literature. Int J Sports Med. 2017 Dec;38(14):1049-1060. doi: 10.1055/s-0043-114861. Epub 2017 Nov 21.

  PMID: 29161748 BACKGROUND

• Kwiecien SY, McHugh MP, Hicks KM, Keane KM, Howatson G. Prolonging the duration of cooling does not enhance recovery following a marathon. Scand J Med Sci Sports. 2021 Jan;31(1):21-29. doi: 10.1111/sms.13822. Epub 2020 Sep 25.

  PMID: 32901996 BACKGROUND

• Sasaki R, Sakamoto J, Kondo Y, Oga S, Takeshita I, Honda Y, Kataoka H, Origuchi T, Okita M. Effects of Cryotherapy Applied at Different Temperatures on Inflammatory Pain During the Acute Phase of Arthritis in Rats. Phys Ther. 2021 Feb 4;101(2):pzaa211. doi: 10.1093/ptj/pzaa211.

  PMID: 33351944 BACKGROUND

• Merrick MA, Rankin JM, Andres FA, Hinman CL. A preliminary examination of cryotherapy and secondary injury in skeletal muscle. Med Sci Sports Exerc. 1999 Nov;31(11):1516-21. doi: 10.1097/00005768-199911000-00004.

  PMID: 10589851 BACKGROUND

• Allan R, Malone J, Alexander J, Vorajee S, Ihsan M, Gregson W, Kwiecien S, Mawhinney C. Cold for centuries: a brief history of cryotherapies to improve health, injury and post-exercise recovery. Eur J Appl Physiol. 2022 May;122(5):1153-1162. doi: 10.1007/s00421-022-04915-5. Epub 2022 Feb 23.

  PMID: 35195747 BACKGROUND

• Kwiecien SY, McHugh MP. The cold truth: the role of cryotherapy in the treatment of injury and recovery from exercise. Eur J Appl Physiol. 2021 Aug;121(8):2125-2142. doi: 10.1007/s00421-021-04683-8. Epub 2021 Apr 20.

  PMID: 33877402 BACKGROUND

• Dubois B, Esculier JF. Soft-tissue injuries simply need PEACE and LOVE. Br J Sports Med. 2020 Jan;54(2):72-73. doi: 10.1136/bjsports-2019-101253. Epub 2019 Aug 3. No abstract available.

  PMID: 31377722 BACKGROUND

MeSH Terms

Conditions

Pain

Interventions

Cryotherapy

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Alvaro N Gurovich, PT, PhD

CONTACT

915-747-7248; agurovich@utep.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chair

Model Details: This study is a randomized, double-blind, controlled clinical trial with 3 independent groups.

Study Record Dates

• First Submitted: October 1, 2025
• First Posted: October 8, 2025
• Study Start: October 15, 2025
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): May 15, 2026
• Last Updated: October 8, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)