Optimizing soft tissue injury rehabilitation: PEACE & LOVE with vs without cryotherapy—protocol for a sham-controlled randomized trial in acute lateral ankle sprain

Abstract

Background

Acute lateral ankle sprains, especially those affecting the anterior talofibular ligament (ATFL), are one of the most frequent injuries in athletes and active adults. These injuries cause pain, swelling, functional restriction, and high recurrence. The PEACE & LOVE framework discourages the use of cryotherapy, yet ice remains widely used in sports and rehabilitation practice. To date, there is limited high-quality evidence evaluating the effect of cryotherapy within this framework. This trial is designed to investigate whether adding cryotherapy to PEACE & LOVE rehabilitation improves outcomes compared with sham cryotherapy.

Methods

This single-center, parallel-group, sham-controlled randomized clinical trial will include 60 physically active adults (aged 18–40 years) with grade I–II acute lateral ankle sprains sustained within 48 h. Recruitment has not commenced and is planned from March to May 2026. Follow-up assessments will continue through 12 weeks post-randomization. Participants will be randomly assigned (1:1) to receive either PEACE & LOVE plus cryotherapy (0–4 °C, 20 min, three times daily for 72 h) or PEACE & LOVE plus sham cryotherapy (identical packs at ~20–25 °C with insulation). The primary outcome is pain intensity measured by the Numeric Pain Rating Scale (NPRS) at day 7. Secondary outcomes are functional recovery measured by the Lower Extremity Functional Scale (LEFS) at day 14, week 4, and week 12; ankle swelling assessed by figure-of-eight measurement at baseline and day 7; ankle dorsiflexion via the Weight-Bearing Lunge Test (WBLT) at baseline, week 4, and week 12; short-term analgesic use (paracetamol log, day 0–7); and re-injury rates assessed at week 4 and week 12. Analyses will follow the intention-to-treat principle using ANCOVA adjusted for baseline scores, reporting effect sizes and 95% confidence intervals.

Discussion

This trial will be the first sham-controlled randomized study to evaluate cryotherapy as an adjunct to the PEACE & LOVE framework in acute ankle sprain. Findings will clarify whether cryotherapy provides clinically meaningful benefits in pain relief, function, and recurrence prevention, and may guide evidence-based rehabilitation practice.

Trial registration

Clinical Trial Registry India (CTRI): CTRI/2024/09/073357. Registered on April 9, 2024.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13063-026-09755-8.

Background

Lateral ankle sprain is one of the most frequent musculoskeletal injuries in athletes and physically active individuals, accounting for up to 40% of all sports-related injuries [1]. Among the lateral ligaments, the anterior talofibular ligament (ATFL) is most commonly injured, particularly in inversion trauma, and is associated with pain, swelling, functional limitations, and a high rate of recurrence if not managed properly [2, 3]. Epidemiological studies suggest that nearly one-third of individuals who sustain an acute ankle sprain will develop residual symptoms or chronic ankle instability, which can significantly impair sporting performance and quality of life [4].

Traditional management strategies for acute ankle sprain emphasized the RICE (rest, ice, compression, elevation) and later POLICE (protection, optimal loading, ice, compression, elevation) approaches [5, 6]. However, more recently, the PEACE & LOVE framework was proposed as a comprehensive, evidence-informed guideline for soft-tissue injuries, to promote optimal tissue healing and long-term recovery [7]. A central recommendation within this framework is to avoid anti-inflammatory modalities, including NSAIDs and cryotherapy, on the basis that suppressing inflammation may disrupt the natural healing cascade. While biologically plausible, this recommendation remains controversial, as cryotherapy is still widely used in sports medicine for its analgesic and anti-edema effects [5]. While PEACE & LOVE represents an evolution from earlier models, its recommendation to avoid cryotherapy remains primarily theoretical, with limited direct evidence comparing outcomes within this specific framework [7, 8]. This uncertainty underscores the need for the present trial.

Clinical evidence on cryotherapy’s role in ankle sprain rehabilitation remains inconclusive. Some trials have reported short-term reductions in pain and swelling [8], whereas systematic reviews have found limited or inconsistent evidence for meaningful functional improvements [9]. Moreover, few studies have examined cryotherapy specifically within the context of modern rehabilitation frameworks such as PEACE & LOVE. This sham-controlled design represents a methodological advance over previous studies, minimizing expectation bias.

Given this gap, a rigorously designed randomized controlled trial is warranted to evaluate whether cryotherapy, when integrated into the PEACE & LOVE framework, provides additional benefits compared to sham cryotherapy in patients with an acute ATFL sprain. This trial is expected to provide high-quality evidence that may inform clinical guidelines and resolve ongoing debate in sports rehabilitation practice.

Methods/design

Study design

This single-center, parallel-group, assessor- and patient-blinded sham-controlled randomized clinical trial will be conducted at the Musculoskeletal Physiotherapy and Sports Rehabilitation Unit, Jashore University of Science and Technology, Bangladesh. Recruitment has not commenced and is planned from March to May 2026. The intervention will involve a 72-h cryotherapy or sham cryotherapy protocol delivered alongside the PEACE & LOVE rehabilitation framework, with follow-up assessments extending to 12 weeks. Participants will be assigned to either an intervention group receiving the PEACE & LOVE framework plus cryotherapy or a control group receiving the PEACE & LOVE framework plus sham cryotherapy. Randomization will be conducted in a 1:1 ratio using a computer-generated allocation sequence with concealed envelopes. Because of the visible temperature difference between ice and sham packs, treating physical therapists cannot be blinded; however, both participants and outcome assessors will remain blinded to minimize bias. The protocol follows the recommendations of the Consolidated Standards of Reporting Trials 2025 (CONSORT 2025) (Fig. 1) and the Standard Protocol Items for Randomized Trials 2025 (SPIRIT 2025) to ensure methodological rigor and transparency.

Fig. 1.

CONSORT 2025 flow diagram

Study setting

The trial will take place at the Musculoskeletal Physiotherapy and Sports Rehabilitation Unit of Jashore University of Science and Technology (JUST), Bangladesh. This facility provides outpatient rehabilitation services for musculoskeletal and sports injuries, receiving referrals from university teams, local athletic clubs, and the surrounding community. Conducting the study in this environment ensures the recruitment of an adequate number of ankle-sprain cases while reflecting the clinical reality of a resource-limited setting.

Study population

The study population will consist of physically active adults aged 18 to 40 years, defined as engaging in moderate-to-vigorous physical activity ≥150 min per week or participating in sports ≥2 times per week, as assessed using the International Physical Activity Questionnaire (IPAQ) short form [10], who present with an acute lateral ankle sprain involving the anterior talofibular ligament (ATFL). All participants will be clinically assessed at presentation to confirm eligibility. Recruitment will occur consecutively through outpatient visits and sports-related injury referrals at the study site. Written informed consent will be obtained before participation.

Sample size calculation

The sample size was calculated using G*Power version 3.1.9.7 (Heinrich Heine University, Düsseldorf, Germany) for the primary outcome of pain intensity (NPRS) at day 7. The calculation was based on a two-tailed independent samples t-test (test family: t-tests; statistical test: means—difference between two independent means), with α = 0.05, power (1 − β) = 0.80, and an allocation ratio (N2/N1) of 1. The effect size (Cohen’s d = 0.80) was derived from the minimal clinically important difference of 2.0 points [11], and an estimated standard deviation of 2.5 from previous ankle sprain research [8] (d = 2.0/2.5). The required sample size was 26 participants per group (total N = 52). Anticipating a 15% attrition rate based on similar trials [12], we increased the target sample size to 30 participants per group (60 total). The primary analysis will use ANCOVA adjusted for baseline scores, which can improve precision compared with analyses that ignore baseline values [13]. This sample size also provides sufficient precision for secondary outcome measures, including the Lower Extremity Functional Scale [14].

Recruitment and screening procedures

Participants will be recruited from the Musculoskeletal Physiotherapy and Sports Rehabilitation Unit at Jashore University of Science and Technology (JUST), Jashore. Recruitment has not commenced and enrollment is planned from March to May 2026. Recruitment will also include referrals from university sports teams and local athletic clubs. Eligible participants will be assessed for suitability based on the inclusion and exclusion criteria outlined in the protocol. The recruitment window aligns with periods of heightened sports participation in the local setting, supporting adequate participant availability.

The recruitment process will follow these steps:

1. A research assistant will pre-screen individuals presenting with ankle injuries to confirm that the onset was within 48 h and that the mechanism is consistent with a lateral ankle sprain.

2. The Ottawa Ankle Rules will be applied to exclude suspected fractures; radiographs will be requested where indicated.

3. Potentially eligible individuals will be informed about the study objectives, procedures, potential benefits and risks, and their rights as participants.

4. After receiving a clear explanation, those willing to participate will provide written informed consent.

5. Participants who consent will undergo baseline assessments, including pain intensity (NPRS), function (LEFS), ankle swelling (figure-of-eight measurement), and dorsiflexion range (Weight-Bearing Lunge Test), performed by blinded assessors.

6. Following baseline testing, participants will be randomly allocated to either the experimental group (PEACE & LOVE plus cryotherapy) or the control group (PEACE & LOVE plus sham cryotherapy) using a computer-generated randomization system with allocation concealment.

This structured process ensures that only eligible participants are enrolled, while minimizing selection bias and ensuring fairness in treatment allocation.

Eligibility criteria

The inclusion and exclusion criteria are structured to ensure that only appropriate participants are enrolled in the trial.

Inclusion criteria

Participants will be eligible if they meet the following conditions: (1) adults aged 18–40 years [2], (2) presentation with an acute lateral ankle sprain (grade I or II) involving the anterior talofibular ligament (ATFL) [1], (3) injury onset within 48 h before recruitment [12], and (4) ability to understand study procedures and provide written informed consent.

Exclusion criteria

Participants will be excluded if they meet any of the following conditions: (1) evidence of fracture identified by the Ottawa Ankle Rules or confirmed by radiography [15], (2) history of ankle surgery or clinical signs of chronic ankle instability [4], (3) presence of systemic inflammatory, neurological, or musculoskeletal disorders likely to interfere with ankle function or rehabilitation [3], (4) contraindications to cryotherapy, such as Raynaud’s phenomenon, cold urticaria, or peripheral vascular disease [8], (5) current use of non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or opioid analgesics, as these may influence inflammation and pain outcomes [7], (6) pregnant or breastfeeding women, and (7) inability or unwillingness to comply with treatment protocols or follow-up assessments.

Sampling technique

A total of 60 participants with acute lateral ankle sprain will be enrolled from the Musculoskeletal Physiotherapy and Sports Rehabilitation Unit at Jashore University of Science and Technology (JUST), Jashore, Bangladesh. Individuals meeting the predefined eligibility criteria will be recruited using a consecutive sampling approach, which ensures accessibility and feasibility within the specified recruitment window. Following recruitment, participants will be randomly assigned to one of two groups: the experimental group (n = 30), receiving the PEACE & LOVE rehabilitation framework combined with cryotherapy; and the control group (n = 30), receiving PEACE & LOVE rehabilitation combined with sham cryotherapy. Allocation will be carried out using a computer-generated randomization sequence to minimize selection bias and maintain balanced group sizes. Each participant will be given a unique identification code (e.g., E1–E30 for the experimental group and C1–C30 for the control group) to safeguard allocation integrity and streamline data management. The randomization procedure will be overseen by a research assistant who is not involved in either treatment delivery or outcome assessment, thereby ensuring allocation concealment and methodological rigor throughout the trial.

Blinding

To reduce bias and maintain the integrity of study outcomes, a double-blind approach will be employed. Participants will be blinded to group allocation by the use of visually identical cryotherapy and sham packs. Allocation will be revealed only to the treating physical therapist, who will prepare and apply the assigned intervention according to standardized instructions. Because of the treatment’s visible characteristics, physical therapists cannot be blinded; however, they will not take part in outcome assessments. Outcome assessors will be separate, blinded physical therapists who do not participate in treatment delivery. Outcome assessors, responsible for collecting pain, functional, and performance data, will also remain blinded to allocation. To preserve blinding during statistical analysis, data will be coded by group identifiers rather than treatment labels. This design minimizes the risk of performance and detection bias by limiting the influence of participant expectations and assessor knowledge on trial outcomes, while ensuring strict adherence to standardized rehabilitation protocols across groups. Unblinding will only be permissible if required for participant safety (e.g., suspected intervention-related adverse events); in such cases, the principal investigator will authorize unblinding for that participant, and the date, reason, and personnel involved will be documented.

Details of the intervention

Two licensed physical therapists, each with more than 7 years of clinical experience in musculoskeletal and sports rehabilitation, will deliver the study interventions. Both therapists will be trained to deliver the PEACE & LOVE rehabilitation program consistently. To maintain treatment fidelity, regular cross-checks of treatment sessions will be performed, and a researcher not involved in intervention delivery will audit adherence to the protocol. The intervention period will last for 12 weeks, with supervised sessions provided three times per week for the first 4 weeks, followed by structured home-based continuation. Each supervised session will last 30–45 min.

Experimental group: PEACE & LOVE + cryotherapy

Participants in this group will receive the standard PEACE & LOVE rehabilitation framework combined with cryotherapy. Cryotherapy will be administered using gel packs cooled to 0–4 °C, applied to the injured ankle for 20 min, three times daily, during the first 72 h after randomization. A protective layer (e.g., a towel) will be used to avoid skin irritation [8]. The PEACE & LOVE program will include the following components [7]:

• Protection: Relative rest for the first 1–3 days, avoiding activities that provoke pain (>2/10 on NPRS) or instability.

• Elevation: Keeping the ankle elevated above heart level for 15–20 min, 3–4 times daily, to limit swelling.

• Avoid anti-inflammatory modalities: Participants will be advised not to use NSAIDs; cryotherapy will only be administered as part of the study intervention.

• Compression: Elastic bandage (tensor bandage) will be applied for 48–72 h post-injury, removed for cryotherapy applications.

• Education: Participants will receive standardized counseling covering: (1) expected recovery timeline (2–6 weeks for grade I, 4–12 weeks for grade II), (2) pain management strategies without NSAIDs, (3) activity modification guidelines, (4) warning signs requiring medical attention (increased pain, swelling, or fever).

• Load: Gradual reintroduction of weight-bearing as tolerated, with progression criterion of pain ≤2/10 on the NPRS during activities.

• Optimism: Positive recovery messaging will emphasize typical recovery trajectories and address fear of re-injury.

• Vascularization: Early cardiovascular activities, including stationary cycling (initial 5–10 min at low resistance, RPE 3–4/10), were introduced within pain-free limits (pain ≤ 2/10 NPRS). Progression: increase duration by 2–3 min every 2–3 days if pain remains ≤2/10.

• Exercise: Progressive rehabilitation following four phases:

  • ◦
    Phase 1 (1–2 weeks): Isometric contractions, ankle alphabets, pain-free range of motion (defined as movement eliciting ≤2/10 NPRS without sharp pain).
  • ◦
    Phase 2 (weeks 3–4): Resistance band exercises (inversion/eversion, dorsiflexion/plantarflexion), single-leg balance, progressive weight-bearing.
  • ◦
    Phase 3 (5–8 weeks): Calf raises, wobble board training, functional activities (walking, light jogging).
  • ◦
    Phase 4 (weeks 9–12): Jumping drills (vertical, horizontal), sport-specific movements, return-to-sport training.

Progression criteria: Advancement to next phase requires pain <3/10 NPRS during exercises, no increase in swelling, and ability to perform current-phase exercises with proper form.

Home-care and adherence monitoring

All participants will receive a printed exercise booklet with illustrations and instructions. Daily diaries will record pain levels (NPRS), exercise completion, and adverse effects. Weekly telephone check-ins (weeks 1–4) and bi-weekly calls (weeks 5–12) will monitor adherence and address concerns.

Control group: PEACE & LOVE + sham cryotherapy

This group will receive the identical PEACE & LOVE rehabilitation program (including all education, exercise progression, and home-care components) with sham cryotherapy. Visually identical gel packs will be maintained at ambient temperature (20–25 °C) and insulated to mimic the intervention group’s packs without tissue cooling. Application frequency and duration will match the experimental group (20 min, three times daily for 72 h) [9]. All other rehabilitation components remain identical between groups.

Outcome measures and assessment points

Socio-demographic information

A structured questionnaire will be used to collect participants’ socio-demographic and clinical characteristics. These will include age, sex, limb dominance, type of sport or physical activity, mechanism of injury, duration since injury, and relevant medical history. This information will help describe the study population and serve as potential covariates in exploratory analyses [1].

Primary outcome

1. Pain intensity: Pain will be measured using the Numeric Pain Rating Scale (NPRS, 0–10), where 0 represents no pain and 10 represents the worst pain imaginable. NPRS is valid and responsive in musculoskeletal conditions, with a minimal clinically important difference (MCID) of approximately 2 points [11]. Measurements will be taken at baseline, day 7 (primary endpoint), day 14, week 4, and week 12.

Secondary outcomes

• 2.Functional status: Function will be assessed with the Lower Extremity Functional Scale (LEFS), a 20-item questionnaire scored on a 0–80 scale. The LEFS has high test–retest reliability (ICC = 0.94) and a reported MCID of 9 points [14]. Assessments will occur at baseline, day 14, week 4, and week 12.
• 3.Ankle swelling: Swelling will be measured using the figure-of-eight method with a flexible tape measure, which has excellent intra- and interrater reliability (ICC > 0.95) [16]. This will be recorded at baseline and day 7.
• 4.Ankle dorsiflexion: Dorsiflexion range will be assessed using the Weight-Bearing Lunge Test (WBLT), recorded in centimeters. The WBLT is reliable and sensitive to change, with ICC values ranging from 0.80 to 0.99 [17]. Assessments will be conducted at baseline, week 4, and week 12.
• 5.Analgesic use: A short medication log will be maintained to record paracetamol consumption (number of tablets per day) from day 0 to day 7. This provides context for interpreting NPRS outcomes while avoiding anti-inflammatory drugs in line with PEACE & LOVE [7].
• 6.Re-injury: Recurrent sprains will be documented at week 4 and week 12 through self-report, verified by clinical assessment. Re-injury is a critical endpoint given that up to one-third of ankle sprains recur within the first year [4].

Study procedure and data collection methods

Participants meeting eligibility will be screened by trained data collectors, given a full explanation of the study, and enrolled after signing written informed consent. Baseline assessments will record socio-demographic details and clinical history, along with standardized measures of pain (NPRS), ankle dorsiflexion (WBLT), swelling (figure-of-eight), and functional status (LEFS). Two blinded assessors from participating centers will conduct these assessments using structured case report forms to ensure uniformity. Once baseline evaluations are complete, participants’ files will be collected, and randomization will be performed using a concealed allocation process. Interventions will then be delivered according to group assignment. Follow-up assessments will be conducted at 4 and 12 weeks, repeating the primary and secondary outcome measures, along with muscle strength, endurance, analgesic use, and re-injury checks. The quality of the interventional study, including the study procedure and data collection methods, will be maintained by following the Standard Protocol Items: Interventional Trials 2025 (SPIRIT) criteria (Table 1).

Table 1.

Overview of standard procedure and data collection according to Standard Protocol Items: Interventional Trials 2025 (SPIRIT) criteria

Abbreviations: NPRS Numeric Pain Rating Scale, LEFS Lower Extremity Functional Scale, WBLT Weight-Bearing Lunge Test

–T1, pre-study screening; T0, randomization; T1, baseline prior to intervention; T2, day 7 post-baseline; T3, day 14 post-baseline; T4, 4 weeks post-baseline; T5, 12 weeks post-baseline

Data management

Data integrity will be safeguarded through routine checks for completeness and accuracy. After each assessment, outcome data will be double-checked by assessors to minimize transcription errors. Hard-copy forms will be securely stored in locked cabinets accessible only to the principal investigator, while electronic data will be stored on a password-protected server at Jashore University of Science and Technology (JUST). Each participant will be assigned a unique study ID, and all outcome data will be recorded using these codes. A separate, password-protected document linking names with study IDs will be maintained apart from the dataset. Only de-identified data will be used for statistical analysis, and results will be presented in aggregate form to protect confidentiality.

Statistical analysis

All analyses will be performed using SPSS version 25.0 (IBM Corp., Armonk, NY, USA). Data distribution will be examined using the Shapiro–Wilk test, skewness, and kurtosis. Descriptive statistics (mean ± SD, frequency, and percentage) will summarize baseline characteristics. Between-group differences in primary and secondary outcomes will be analyzed using ANCOVA, adjusting for baseline values [13]. When data are not normally distributed, equivalent non-parametric methods will be applied. Within-group changes will be tested using paired t-tests or Wilcoxon signed-rank tests. All analyses will follow the intention-to-treat principle, with missing data handled using multiple imputation where feasible. Effect sizes with 95% confidence intervals will be reported alongside p values to aid interpretation. Multiple imputation by chained equations (MICE) with 5 imputations will handle missing data, assuming missing at random (MAR). Sensitivity analyses will compare complete-case with imputed datasets. Exploratory subgroup analyses will examine effects by injury grade (I vs II) and activity level (IPAQ category).

Monitoring

A monitoring team of two individuals not directly involved in recruitment or treatment will oversee trial conduct. Their responsibilities will include auditing intervention delivery, reviewing adherence, monitoring for adverse events, and conducting interim checks on data quality. Any modifications in methodology will be reported by the principal investigator to the Institutional Review Board (IRB). No interim analyses or formal stopping guidelines are planned for this trial.

Safety measures and adverse effect management

No serious adverse events are anticipated from cryotherapy or sham procedures. However, participants will be informed about possible short-term issues such as skin irritation, numbness, or discomfort [8]. Any adverse events will be documented by the treating physical therapist in clinical notes and reported to the principal investigator within 24 h. Serious adverse events, if any, will be immediately communicated to the IRB. Participants developing contraindications during the trial will be withdrawn and referred for appropriate care.

Ethical issues and informed consent

Ethical approval for this study was granted by the Institutional Review Board of Jashore University of Science and Technology (Approval No. PTR-JUST/IRB/2024/01/192418). The trial was prospectively registered with the Clinical Trial Registry India (CTRI/2024/09/073357). All procedures complied with the Declaration of Helsinki. Written informed consent was obtained from all participants, who were informed of their right to withdraw at any stage without affecting their clinical care. Participant confidentiality was strictly maintained, and access to anonymized data was limited to authorized study personnel. In the event of any adverse outcomes, appropriate care was provided.

Trial status

This protocol is version 1.0, dated 22 September 2025. Recruitment has not commenced, and enrollment is planned from March to May 2026. Final follow-up is expected to be completed by August 2026.

Dissemination

Study findings will be disseminated through multiple channels: (1) peer-reviewed open-access publications; (2) presentations at national and international sports physical therapy conferences; (3) workshops for clinicians to integrate findings into practice; and (4) institutional seminars at JUST to share knowledge with researchers and students. Dissemination will follow open science principles to ensure accessibility to clinicians, athletes, and researchers.

Discussion

Ankle sprains remain one of the most prevalent musculoskeletal injuries in sports and recreational activities, with the anterior talofibular ligament (ATFL) being the most commonly affected structure [1, 2]. Despite their frequency, optimal management strategies remain debated, particularly regarding the role of cryotherapy. The recently proposed PEACE & LOVE framework discourages anti-inflammatory modalities, including cryotherapy, on the grounds that suppressing the inflammatory process may hinder tissue healing [7]. However, this recommendation is largely based on theoretical reasoning, and clinical evidence directly examining cryotherapy within this framework is limited and inconclusive [8, 9].

This trial is designed to address this knowledge gap by evaluating whether cryotherapy provides additional benefits when combined with the PEACE & LOVE protocol. By employing a sham-controlled, double-blind design, the study aims to minimize performance and detection biases, which have limited previous trials. The choice of day 7 NPRS as the primary endpoint targets the acute stage when cryotherapy is hypothesized to be most effective, while longer-term assessments at 2, 4, and 12 weeks will provide insight into durability and recurrence rates. The inclusion of validated functional and performance measures, such as the Lower Extremity Functional Scale (LEFS) and Weight-Bearing Lunge Test (WBLT), strengthens the ecological relevance of findings for clinical and sports rehabilitation practice.

Several methodological strengths enhance the credibility of this study: (1) standardized interventions delivered by trained physiotherapists, (2) blinding of participants and assessors through the use of sham cryotherapy, (3) prospective registration and adherence to CONSORT and SPIRIT guidelines, and (4) intention-to-treat analysis with ANCOVA adjustment for baseline scores. Nonetheless, several limitations should be acknowledged. As a single-center study, generalizability to other settings or populations may be restricted. The relatively small sample size, although adequately powered for the primary outcome, may limit the detection of rare adverse events or subgroup effects. The three-month recruitment window (March–May 2026) may not capture seasonal variations in injury patterns. Adherence to home-based rehabilitation may vary despite treatment diaries and follow-up calls. Additionally, the absence of inflammatory biomarker assessment prevents mechanistic interpretation of cryotherapy’s effects. Finally, while participants and assessors are blinded, treating physiotherapists cannot be blinded due to the nature of the intervention, introducing potential performance bias.

Despite these challenges, this study is expected to provide high-quality evidence on the role of cryotherapy in the rehabilitation of acute ankle sprains. If cryotherapy demonstrates additional benefit, it could challenge current recommendations under the PEACE & LOVE model and reinforce its place in early rehabilitation. Conversely, if no advantage is found, the results will support minimizing its use in favor of evidence-based functional interventions.

Conclusion

This randomized, sham-controlled trial will be the first to rigorously evaluate the effect of cryotherapy as an adjunct to the PEACE & LOVE framework in the management of acute lateral ankle sprains. The study’s design addresses prior methodological shortcomings and integrates both patient-reported and objective outcomes. The findings will provide critical evidence to guide clinicians, athletes, and policymakers on whether cryotherapy offers meaningful benefits in acute ankle sprain rehabilitation. Ultimately, the trial aims to inform best-practice guidelines and contribute to the ongoing refinement of evidence-based sports physical therapy.

Abbreviations

ANCOVA

Analysis of covariance

ATFL

Anterior talofibular ligament

CONSORT

Consolidated Standards of Reporting Trials

CTRI

Clinical Trial Registry India

ICC

Intraclass correlation coefficient

IRB

Institutional Review Board

JUST

Jashore University of Science and Technology

LEFS

Lower Extremity Functional Scale

MCID

Minimal clinically important difference

NPRS

Numeric Pain Rating Scale

NSAIDs

Non-steroidal anti-inflammatory drugs

PEACE & LOVE

Protection, Elevation, Avoid anti-inflammatory modalities, Compression, Education, Load, Optimism, Vascularization, Exercise

SPIRIT

Standard Protocol Items: Recommendations for Interventional Trials

SPSS

Statistical Package for the Social Sciences

WBLT

Weight-Bearing Lunge Test

Authors’ contributions

PH conceived the study, prepared the initial draft of the protocol, and coordinated manuscript preparation. MZH supervised the project, contributed to study conception and design, and critically revised the protocol. MAAA contributed to drafting specific sections of the manuscript and supported the literature review. JS assisted in protocol development and editing. MFK contributed to refining the methodology and manuscript revision. KMAH participated in study design discussions and reviewed the draft manuscript. SJ contributed to protocol editing and ensured consistency across sections. KH supported literature review and manuscript preparation. TH contributed to drafting sections related to methodology and protocol flow. ER (corresponding author) provided overall supervision, guided protocol development, and critically reviewed the manuscript for intellectual content. All authors contributed to the conception and design of the study, as well as drafting and revising the manuscript. All authors approved the final version of the manuscript and agree to be accountable for the integrity and accuracy of the work.

Funding

This trial is self-funded by the authors. No external funding sources were involved in the design, conduct, data collection, analysis, or manuscript preparation.

Data availability

The de-identified dataset generated and analyzed during this trial will be available from the corresponding author upon reasonable request. Requests will require approval from the principal investigator to ensure compliance with ethical and data protection requirements. This article contains the full trial protocol; no separate statistical analysis plan has been prepared, and all planned analyses are described in the Statistical analysis section of this protocol.

Declarations

Ethics approval and consent to participate

This protocol received approval from the Institutional Review Board of Jashore University of Science and Technology, Bangladesh, on July 1, 2024 (Approval No. PTR-JUST/IRB/2024/01/192418). The trial is prospectively registered with the Clinical Trial Registry India (CTRI/2024/09/073357). Written informed consent will be obtained from all participants before enrollment. Participation is voluntary, and individuals may withdraw at any stage without consequences for their care. All study procedures will adhere to the principles outlined in the Declaration of Helsinki.

Consent for publication

Participants will be informed that anonymized data from this trial may be published. Written consent for publication will be obtained as part of the informed consent process. No identifiable data will be published.

Competing interests

The authors declare that they have no financial or personal conflicts of interest that could influence the conduct or reporting of this study.