Isometric exercises do not provide immediate pain relief in Achilles tendinopathy: A quasi‐randomized clinical trial (2024)

2.1. Study design

This quasi‐randomized clinical trial with four intervention arms was conducted as a part of a randomized clinical trial (RCT). The aim of this larger RCT was to evaluate the effect of a high‐volume injection in patients with chronic midportion AT (ClinicalTrials.gov Identifier: NCT02996409). The current study was performed before patients received any type of intervention, and the outcome of the current study did not affect participation in the larger RCT. All patients provided written informed consent prior to participation. The protocol of the study was approved by the regional Medical Ethical Committee (registration number 14‐100). Study findings are reported following the CONSORT guideline, the Pain specific CONSORT supplement checklist, and the TIDieR guideline for reporting interventions. Originally, the aim was to compare three intervention arms: isometric exercises (tiptoes), isotonic exercises, and rest. During the course of the study, there was enhanced insight in this research field that the joint position could influence the analgesic effect as previous research demonstrated that tendon loading varies at different joint positions.23 Therefore, we decided to add an intervention arm in which isometric exercises were performed with the ankle dorsiflexed.

2.2. Setting and subjects

This clinical trial was performed at the Sports Medicine department in a large district general hospital (Haaglanden Medical Center, Leidschendam, the Netherlands) and a university medical center (Erasmus MC University Medical Center, Rotterdam, the Netherlands). All 80 patients who were included in the RCT participated also in the current study. Additionally, patients with AT who presented after inclusion of the larger RCT was completed were allowed to still participate when visiting one of these research centers. Inclusion was carried out by two sports medicine physicians. Inclusion criteria were as follows: (a) the presence of chronic midportion AT for at least 2months, (b) no subjective symptomatic improvement after exercise therapy of at least 6weeks, (c) aged between 18‐70years, and (d) the presence of Doppler flow on power Doppler ultrasonography. The diagnosis was established based on clinical examination (local tendon pain and swelling of the Achilles tendon 2‐7cm proximal to its calcaneal insertion, and impaired load‐bearing capacity) by the sports medicine physician. The main exclusion criteria were as follows: (a) a clinical suspicion of other musculoskeletal disorders (insertional AT, inflammatory internal disorders, quinolone‐, corticosteroid‐ or statin‐induced tendinopathy), (b) a previous Achilles tendon rupture or surgery, (c) the inability to perform an exercise program, and (d) a medical condition that could affect the safety of the injection in the larger RCT (eg, peripheral vascular disease or use of anticoagulant medication). Detailed information regarding all eligibility criteria is provided in the trial registration. In case of bilateral symptoms, the patient selected the most symptomatic tendon for inclusion in this study.

2.3. Quasi‐randomization

Patients were originally allocated to one of the three intervention arms based on the inclusion number in the larger RCT. Using this method of quasi‐randomization, all patients were equally distributed between the groups. The last 11 participants in the larger RCT and seven extra patients who visited the outpatient department for clinical care (18 in total) were allocated to the additional intervention arm performing isometric exercises with a dorsiflexed position of the ankle.

2.4. Interventions

The intervention arms consisted of a specific loading protocol or a period of rest. Patients were told that the loading exercises were performed to determine the maximum amount of weight that could be lifted to personalize the exercise program for the following weeks. Patients in the rest group were asked to sit on a chair while they received verbal instructions regarding the exercise program for the following weeks. The hypothesis of the current study was therefore unknown to all participants. Instructions were provided by a single non‐blinded, trained PhD candidate with 2years of practical medical training who included patients at both research centers. The interventions were based on previous work in this research field.18, 21 Of a total of four intervention arms, three groups performed plantar flexor contractions both in seated and standing position and the control group rested. The different loading protocols are presented in Table1. The duration of all programs was identical (13minutes). Prior to the programs, patients completed a warming‐up consisting of walking up and down four flights of stairs followed by 1minute of non‐loaded mobility exercises of the ankle. Patients were subsequently instructed that exercises should be performed at maximal intensity and may be painful. Patients were instructed to ignore pain unless it was unbearable. Patients started with an additional weight of 30kg for the first set in seated position of the loading protocols. Standardized feedback was provided during the loading protocols (“come‐on, half‐way there”).

Table 1

Interventions used in the study

	Joint position (degrees of flexion)	Sets/duration	Recovery (min)	Example of setup in standing position
Isometric (tiptoes)
Seated	Hip 90°	2×45s	2
	Knee 90°
	Ankle 20°
Standing	Hip 0°	3×45s	2
	Knee 0°
	Ankle 20°
Isometric (dorsiflexed)
Seated	Hip 90°	2×45s	2
	Knee 90°
	Ankle −10°
Standing	Hip 0°	3×45s	2
	Knee 0°
	Ankle −10°
Isotonic
Seated	Hip 90°	2×15 rep	2
	Knee 90°	(both concentric and eccentric phase 1‐2s)
	Ankle 0‐20°
Standing	Hip 0°	3×15 rep	2
	Knee 0°	(both concentric and eccentric phase 1‐2s)
	Ankle 0‐20°
Rest	—	—	13

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Note

For the plantar flexor contraction groups, five sets of exercises were performed, of which two sessions were performed with the knee bent followed by three sessions with the knee extended. Exercises were performed barefoot under supervision of the researcher. All patients rested for 2min between sets to allow sufficient recovery. A stopwatch was used to control for the prescribed contraction and rest times. Joint positions of the ankle are presented as positive numbers for plantarflexion and as negative numbers for dorsiflexion.

Abbreviations: rep, repetitions; s, seconds.

The rate of perceived exertion (RPE) was recorded between sets. A score of 0 indicates rest and a score of 10 maximal effort. If exercises were relatively easy to perform (RPE<7), additional weight was applied using weighted vests up to a maximum of 60kg and adjustable per 1.5kg (in seated position resting on the upper leg). To evaluate intensity of the loading protocols, an overall RPE score for the loading protocol was obtained after the performance of all sets of exercises. The weight was lowered in case of unbearable pain or when patients could not complete the contraction times.

2.5. Test methods

2.6. Statistical analyses

Our sample size calculation showed that 16 patients in each group were required to detect a minimal clinically important difference of 20 points on the VAS score (power 0.80, 2‐sided significance level 0.05, SD 20).21, 28, 29 Data were analyzed using SPSS 25.0.0.1 (SPSS Inc.) according to a statistical analysis plan uploaded on clinicaltrials.gov before evaluating the last patient in the RCT. Within‐group differences of the 10 hop VAS scores were analyzed using a Generalized Estimation Equations (GEE) model. To test whether changes in VAS score before and after the program were different between groups, we added the interaction term of intervention arm*pre/post‐testing. Adjustments were made for the following pre‐defined baseline variables: age, sex, BMI, baseline VISA‐A score, and duration of symptoms. Outcomes of the GEE model are presented as estimated marginal means with their 95% confidence interval, unless otherwise stated. Between‐group differences in the RPE score and the added weight during the loading protocol were analyzed using a one‐way ANOVA test. Differences of P<.05 were considered to be statistically significant. Missing data were not imputed, but we planned to perform sensitivity analyses if missing data would exceed 5% for a certain time point.30

Table 2

Baseline characteristics of the four intervention arms with between‐group P‐values

3.1. Primary outcome measure—patient‐reported pain

The within‐group differences in estimated mean 10 hop VAS score were not statistically significant in all the intervention groups as presented in Table3. Ten hop VAS scores are presented as raw individual patient data and mean scores in Figure2. The interaction term intervention arm*pre/post‐testing was not statistically significant (P=.26), meaning that the change in 10 hop VAS score did not differ between the four groups. Between‐group differences were thus all not statistically significant after the interventions (Table3). The unadjusted analyses are reported in web Appendix 1.

3.2. Success of procedures

The mean (SD) RPE (0‐10) during the loading protocol was 7.0 (1.7) in the isometric (tiptoes) group (n=17), 7.7 (1.2) in the isometric (dorsiflexed) group (n=18), and 7.8 (1.5) in the isotonic group (n=17). The mean (SD) added weight during the loading protocol in seated position was 28kg (7) in the isometric (tiptoes) group, 31kg (4) in the isometric (dorsiflexed) group, and 30kg (4) in the isotonic group. In the standing position, the mean (SD) added weight was 25kg (12) in the isometric (tiptoes) group, 16kg (16) in the isometric (dorsiflexed) group, and 22kg (12) in the isotonic group. Between‐group differences were not statistically significant for the mean RPE (P=.22), the mean added weight in seated position (P=.28), and the mean added weight in standing position (P=.10).

4.1. Summary of main findings

Our trial compared the effects of two different isometric exercises, isotonic exercises, or resting on pain during a functional test in chronic midportion Achilles tendinopathy. Neither isometric nor isotonic exercises provided an immediate analgesic effect.

4.2. Clinical implications

Our findings are important and clinically relevant, since the performance of isometric exercises has become increasingly popular as initial treatment and for immediate pain relief in several lower‐limb tendinopathies. The popularity is based on a study that found a large and meaningful decrease in pain score of 6.8 (scale 0‐10) following isometric exercises in patients with patellar tendinopathy, compared to a decrease of 2.6 points following isotonic exercises.18 Despite the fact that this was a single study with a very small sample size (n=6), isometric exercises were implemented rapidly.20 Results were quickly extrapolated to other lower‐limb tendinopathies such as AT.20

To date, one other research group investigated the analgesic effect of isometric exercises in a relatively small group of patients (n=16) with chronic midportion AT. Heterogeneous individual responses were found, with no overall meaningful change in pain scores during a functional task after performing isometric exercises.21 A difference between that particular study and ours is that in the previous study patients performed exercises using a Wii platform. We performed the exercises in the way they are performed in the clinical setting during rehabilitation with the use of additional weight. Comparable results with no meaningful change were also found in patients with lateral elbow tendinopathy, plantar fasciopathy, and a recent second study in patellar tendinopathy.19, 29, 31 We also demonstrated no meaningful change in pain score after the performance of isometric exercises with either a dorsiflexed or a plantar flexed position of the ankle.

In previous research, isotonic exercises provided immediate pain relief with small magnitude in patellar tendinopathy.18 This is the first study to investigate the possible analgesic effect of isotonic exercises in AT. We also found no meaningful change in pain score after isotonic exercises. Our study was the first to include a rest group in which no exercises were performed. Results of the intervention arms performing a loading protocol did not differ from the rest group, indicating that both isometric and isotonic calf‐muscle exercises have no immediate analgesic effect.

4.3. Research implications

The previous study in patients with chronic midportion AT demonstrated that the severity of symptoms could play a role in the analgesic effect of isometric exercises. Individuals with higher pain scores worsened in that study, compared to individuals with lower pain scores who improved after isometric exercises.21 We did not replicate this finding with our study, as the individual responses to the intervention were very heterogeneous (Figure2). More research would be needed to determine whether subgroups are present and if so, whether different treatment regimens should be provided. This would involve very large study numbers. We did not investigate the role of isometric or isotonic exercises as an actual treatment for AT, and more research regarding the efficacy of the different exercise programs on the intermediate and long‐term effects is necessary.32 Our study shows that both types of exercises also do not aggravate immediate pain. Both exercises are well‐tolerated and could represent a starting point for therapy, self‐efficacy, and self‐management. We also did not investigate the analgesic effect of isometric exercises in patients with a short symptom duration (reactive stage). It could be hypothesized that possible cortical reorganization depends on the chronicity of symptoms, making patients with a chronic symptoms less sensitive to an analgesic effect of isometric exercises.

4.4. Strengths and limitations

This is the largest study to date investigating the immediate analgesic effect of both isometric (two groups with different ankle positions) and isotonic exercises in patients suffering from tendinopathy. This is also the first study to include a control group who rested to rule out an analgesic effect from activation of the musculotendinous unit.

Despite our robust research design, there are some methodological limitations. First, we estimated our sample size on a SD of 20 points. However, it transpired that the SD of the changes in the VAS scores was approximately 26 points and thus 28 patients per group would have been required to detect a meaningful change. Additionally, the secondary outcomes could also be slightly underpowered as multiple testing was performed. If we would adjust the alpha level using the Bonferroni method for a total of 6 comparisons, 41 patients per group would have been required. However, if we overlook the mean between‐group differences and the very few responders, it is unlikely that this study does involve a type II error. Furthermore, the abovementioned potential limitations do not influence our primary aim to determine whether isometric exercises provide an immediate analgesic effect. Second, the method of quasi‐randomization was used to allocate patients to the intervention arms. Although this method is not preferable, it was most appropriate as patients were already being randomized to evaluate the effect of an injection treatment. We also adjusted for relevant pre‐defined baseline variables in the GEE model, making it unlikely that differences in baseline characteristics will have influenced results. Third, it was not feasible to blind the outcome assessor (patients) for the type of intervention. However, we did not mention the hypothesis of the study and in doing so avoided influencing patient beliefs regarding the immediate effect of exercise therapy. Fourth, patient beliefs regarding exercise therapy could already be influenced since absence of symptomatic improvement after exercise therapy at short term (at least 6weeks) was an inclusion criterion. It is, therefore, questionable whether we could extrapolate these results to the broader population of patients with midportion Achilles tendinopathy. Fifth, we did not obtain the RPE scores from the first 20 inclusions. The RPE was still obtained in the majority of the patients (17/24) in both the isometric (tiptoes) group and the isotonic group and in all 18 patients within the isometric (dorsiflexed) group. Sixth, some patients (n=9) had a 10 hop VAS score of zero at the start of the exercise therapy and could thus not show an immediate analgesic effect. Additional sensitivity analyses excluding those patients did not affect outcomes of this study. Future studies are advised to exclude these patients in their trial.

Appendix S1

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