E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
pain with tenderness in the Achilles tendon, but not at the attachment to the heel bone |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050471 |
E.1.2 | Term | Achilles tendon pain |
E.1.2 | System Organ Class | 100000004859 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050129 |
E.1.2 | Term | Achilles tendon thickening |
E.1.2 | System Organ Class | 100000004859 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000435 |
E.1.2 | Term | Achilles tendon injury |
E.1.2 | System Organ Class | 100000004863 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000433 |
E.1.2 | Term | Achilles tendinitis |
E.1.2 | System Organ Class | 100000004859 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000441 |
E.1.2 | Term | Achilles tendonitis |
E.1.2 | System Organ Class | 100000004859 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this research is to determine if the addition of topical GTN over 24 weeks to a 12 week exercise program improves clinical outcomes more than placebo GTN for people with Achilles tendinopathy |
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E.2.2 | Secondary objectives of the trial |
To determine at which time point (week 6, 12 or 24) changes in clinical outcomes occur in those with Achilles tendinopathy undergoing a programme of topical GTN and eccentric exercise.
To determine which baseline measures and patient-specific factors can predict response to treatment (GTN and eccentric exercise).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria: 1. Current diagnosis of Achilles tendinopathy 2. 18 years of age and old 3. Achilles pain of 3 months or more 4. Mid-portion Achilles tenderness and thickening on palpation
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E.4 | Principal exclusion criteria |
1. Previous corticosteroid injection to the affected tendon in the past 3 months 2. Symptoms of less than 3 months duration 3. Previous use of topical GTN for Achilles tendinopathy 4. Contra-indication to GTN therapy 5. Current pregnancy, breastfeeding or planning pregnancy 6. VISA-A score > 80 7. Previous surgery to the affected Achilles tendon 8. Seronegative spondyloarthropathy with Achilles enthesitis 9. Previous performance of a heavy load eccentric exercise program of the Achilles in the last 6 months 10. Inability to perform the exercise program due to serious illness, such as unstable angina/blood pressure, myocardial infarction in past three months, cardiomyopathy, uncontrolled metabolic disease, recent ECG changes, advanced respiratory disease or third degree heart block. 11. Staff or students of Connolly Hospital, Blanchardstown.
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E.5 End points |
E.5.1 | Primary end point(s) |
Participants will perform the exercise program for 12 weeks and will use the patch for 24 weeks. They will complete final assessment after 24 weeks use of the patch. The primary endpoint is the VISA-A scale. 24 weeks after commencing the trial participants will cease to use the topical medication (GTN). The VISA-A will be administered at baseline, week 6, 12 and 24. The primary outcome will be the Victoria Institute of Sport Assessment, Achilles (VISA-A) scale, which measures the impact of Achilles tendinopathy on individuals’ lifestyle. The VISA-A is a valid, reliable and user friendly self-report index of severity of Achilles tendinopathy, can be easily administered in clinical practice (Robinson et al, 2001) and has been used as an outcome measure in other tendinopathy trials (Tumilty et al, 2012). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The VISA-A will be administered at baseline, week 6, 12 and 24. |
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E.5.2 | Secondary end point(s) |
Secondary endpoints are the secondary outcome measures, outlined below:
1. Numerical Rating Scale (NRS)
Participants will be asked to rate their Achilles pain from zero to ten on a numerical rating scale (NRS). Standardized and validated pain scales provide a means of measuring a patient’s pain and of evaluating the response to treatment. Williamson and Hogart (2005) determined that NRS is valid, reliable and appropriate for use in clinical practice. Participants will be asked to verbally rate their level of perceived pain intensity on a numerical scale from 0 to 10, with zero representing “no pain” and 10 representing the “the worst pain possible”.
2. Lower Extremity Functional Scale (LEFS). The LEFS is a self-report measure of functional ability in relation to their Achilles tendinopathy, which will be completed by participants. The LEFS has been shown to have good construct validity and reliability with more sensitivity to change than the SF-36. It is easy to administer and score so is applicable for research purposes and clinical decision making for individual patients (Binkley et al., 1999).
3. Pressure Algometry The outcome measurement in pressure algometry is the pain detection threshold (PDT), or the point at which pressure pain is first experienced by the participant. As tenderness is one of the key clinical diagnostic criteria, algometry is an appropriate measure to quantify the pain pressure response. Participants will be positioned prone with the ankle at neutral position with the foot hanging off the edge of the treatment table. The thickest and most tender point of the Achilles will be identified and marked with a pen. The algometer will be placed against the tender point and pressure gently and steadily increased until such point that the patient experiences pressure pain. The corresponding pressure will be read and recorded. This technique will be used to objectively measure the pain detection threshold (PDT) of affected and unaffected Achilles tendons in all participants.
4. Ultra-sound examination of the Achilles tendon. All Achilles tendons (both affected and unaffected sides) will undergo ultra-sound scans at baseline and weeks 6, 12 and 24. Longitudinal and transverse views will be obtained. The Achilles tendons will be measured with patients in a prone position and their heels overhanging the examination couch to enable movement of the feet (Gibbon et al, 1999; Ohberg et al, 2001). The ankles will be flexed to 90° to ensure standardised tension on the tendon and provide the best imaging during contraction of the gastrocnemius muscles. The tendon thickness will be measured at the thickest point in both longitudinal and transversal scans. In the longitudinal scan, abnormal Achilles tendon thickness will be measured at the thickest point, and the distance from the point of measuring to the attachment of the calcaneus will be recorded.
5. Dynamic Balance/Proprioception testing The modified Star Excursion Balance Test (SEBT) will be performed to assess whether any difference exists between the 2 groups and between the affected and unaffected limbs. The SEBT has been shown to be a reliable measure of dynamic balance (Hertel et al, 2006). Participants will complete the test for each limb in 3 SEBT reach directions (anterior, posteromedial, and posterolateral). This 3 direction version of the SEBT has been termed the Y balance test and has been shown to be a reliable test for measuring single limb stance excursion distances while performing dynamic balance (Plisky et al, 2009). The reach distance will be measured and recorded by the principal investigator. 6. Heel raises for endurance and hopping test The heel raise test for endurance will be performed on one leg at a time with the participant standing. Participants will be instructed to raise up as high as possible onto the toes and then lower the heel to the starting position and repeat this technique for as many as possible on each leg. The test will be terminated when the patient stops, or can no longer perform a heel raise. The number of heel raises and any pain associated with the test will be documented using the NRS. Hopping tests involve the stretch shortening cycle of the Achilles tendon and calf musculature, and therefore measure the muscle tendon units elastic properties. Participants will be instructed to perform hopping on one leg at a time, with arms by the side, in a natural rhythm. Participants will be instructed to perform 20 hops on each leg with 15 to 30 seconds rest between each side. The number of hops performed and pain associated with hopping on each side will be documented using the NRS. Both the heel raise to endurance and hopping test have been shown to reliable tests with good test-retest reliablility in previous studies of Achilles tendinopathy (Silbernagel et al, 2001 and 2006).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary end points will be evaluated at baseline, week 6, 12 and 24. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |