Acute Cryotherapy on Musculoskeletal Function and Biomarkers

Official title

Effects of Acute Cryotherapy on Musculoskeletal Function and Biomarkers for Inflammation, Oxidative Stress, and Muscle Damage

Overview

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.

Detailed description

This study is a randomized, double-blind, controlled clinical trial with 3 independent groups. One group (control-control or CON-CON) will not exercise and will not have any cryotherapy intervention, a second group (control or CON) will exercise but use a "room temperature" cold-pack, and the cryotherapy group (CRYO) will exercise and receive a cold cold-pack every day for 15-min.

We anticipate to compare means in several markers (functional and in blood) using a two-way analysis of variance (ANOVA, time x condition) where time is before, and 0, 24, 48, 72, 96, and 264 hours after exercise (6 visits) and conditions are CON-CON, CON, and CRYO.

VISIT ONE Before the informed consent process, potential participants will rest for 10 minutes, and their blood pressure will be taken to confirm eligibility. Once eligibility is confirmed, participants will go through the informed consent process. After the participants have signed the informed consent, the participants will be randomly allocated to one of the 3 groups. Then, a blood sample (two 10-ml tubes) from an antecubital vein of the dominant arm will be drawn. After the blood drawn, a set of functional tests ( i.e., arm girth, active range of motion (ROM), peak pressure threshold (PPT), and maximal voluntary isometric contraction (MVIC)) will be performed (the description of each test can be found below). Once the functional tests are performed, participants from the CON-CON group will be dismissed. Participants from the other 2 groups will perform a controlled exercise-induced muscle damage (EIMD) through eccentric exercise (protocol description below). Immediately after the EIMD protocol, participants in the CON group will receive 15-min of a room temperature cold-pack in room RSC 100. Participants in the CRYO group will receive 15-min of a cold cold-pack in room RSC 100. Treatment will be performed by RAs that were not involved in any testing session. After treatment, CON or CRYO, the same set of functional tests will be performed in room RSC 117.

VISIT TWO to FOUR (24, 48, and 72 hours after VISIT 1, respectively) Participants will get a blood draw (two 10-ml tubes) from an antecubital vein of the dominant arm. Then, participants in the CON group will receive 15-min of a room temperature cold-pack in room RSC 100. Participants in the CRYO group will receive 15-min of a cold cold-pack in room RSC 100. Treatment will be performed by RAs that were not involved in any testing session. Participants from the CON-CON group will not have any treatment. Finally, the set of functional tests will be performed.

VISIT FIVE (96 hours after VISIT 1) Participants will get only a blood draw (two 10-ml tubes) from an antecubital vein of the dominant arm. Then, participants in the CON group will receive 15-min of a room temperature cold-pack in room RSC 100. Participants in the CRYO group will receive 15-min of a cold cold-pack in room RSC 100. Treatment will be performed by RAs that were not involved in any testing session. Participants from the CON-CON group will not have any treatment.

VISIT SIX (264 hours after VISIT 1) Participants will get a blood draw (two 10-ml tubes) from an antecubital vein of the dominant arm. Then, the set of functional tests will be performed.

Interventions

• Other Cryotherapy
  A cold (-5°C) cold-pack for 15 minutes every 24 hours for 5 days
• Other Eccentric exercise-induced muscle damage
  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.

Primary outcome measures

• Maximal Voluntary Isometric Contraction (MVIC) [Time frame: From enrollment to the end of study at 12 days]
• Peak Pressure Threshold (PPT) [Time frame: From enrollment to the end of study at 12 days.]
• Creatine kinase [Time frame: From enrollment to the end of treatment at 5 days]
• Interleukin-6 [Time frame: From enrollment to the end of treatment at 5 days]
• 8-isoprostane [Time frame: From enrollment to the end of treatment at 5 days]

Secondary outcome measures (3)

• Arm girth [Time frame: From enrollment to the end of study at 12 days.]
• Active Range of Motion (ROM) [Time frame: From enrollment to the end of study at 12 days.]
• C-reactive protein [Time frame: From enrollment to the end of treatment at 5 days.]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Supportive care

Study locations

United States · 1 center

• The University of Texas at El Paso, Rehabilitation Sciences Complex — El Paso

Publications

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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

Identifiers

NCT: NCT07211412 · 2356825

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗