TendinopathyNEATNCT02499484
Topical Glyceryl Trinitrate (GTN) and Eccentric Exercises in the Treatment of Midportion Achilles Tendinopathy
A study testing glyceryl trinitrate and Eccentric exercise program in people with Tendinopathy and Achilles Tendon Pain, run by Royal College of Surgeons, Ireland at 1 site in Ireland.
Trial summary
The primary objective of this research is to determine if the addition of topical GTN over 24 weeks to a 12 week exercise programme improves clinical outcomes more than placebo GTN for people with Achilles Tendinopathy. Pain in the Achilles tendon is a common condition seen by physiotherapists and doctors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tendinopathy, Achilles Tendon Pain
- What is being tested?
- glyceryl trinitrate and Eccentric exercise program
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 76 participants
- Where
- 1 siteIreland
- Study dates
- Sep 2016to Nov 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Current diagnosis of Achilles tendinopathy
- Subjects must be able and willing to give written informed consent and to comply with the requirements of this study protocol
- Subjects must be male or female, aged 18 years or above at Baseline
- Achilles pain of >3 months or more
- Mid-portion Achilles tenderness and thickening on palpation
- Confirmation of the diagnosis upon Ultra-sound assessment, and ruling out of other pathologies (eg: ruptures)
Who cannot join
- Previous corticosteroid injection to the affected tendon in the past 3 months
- Symptoms of less than 3 months duration
- Previous use of topical GTN
- Current use of nitrates, eg: GTN spray, tablet, transdermal patch.
- Contra-indication to GTN therapy (see section 12.2.3)
- Current pregnancy, breastfeeding or planning pregnancy
Show all 14Show fewer
- VISA-A score > 80
- Previous surgery to the affected Achilles tendon
- Seronegative spondyloarthropathy with Achilles enthesitis
- Previous performance of a heavy load eccentric exercise program of the Achilles in the last 2 years
- Severe migraines which fail to respond to over the counter medication and require specific migraine management
- 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.
- Any medical or psychiatric condition that the investigator deems appropriate for exclusion
- Staff or students of Connolly Hospital, Blanchardstown
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Use of Topical Glyceryl Trinitrate (GTN) and Eccentric Exercises in the Treatment of Midportion Achilles Tendinopathy: a Randomized Placebo Controlled Trial
The primary objective of this research is to determine if the addition of topical GTN over 24 weeks to a 12 week exercise programme improves clinical outcomes more than placebo GTN for people with Achilles Tendinopathy.
Pain in the Achilles tendon is a common condition seen by physiotherapists and doctors. It affects people involved in sports and those who are not. It can limit the ability to walk, hop, jump and run. If the pain persists for longer than 3 months it can become extremely difficult to abolish. As a result, people with this common condition can suffer from prolonged pain and often the pain will persist and affect everyday activities.
Read more
While this is an easy injury to diagnose, it is not so easy to treat. Many treatments do exist, but often just provide short-term relief until the pain returns. Specific strengthening exercises have been shown to be beneficial in treating this condition.
The current project will study Achilles tendon pain in Irish adults at Connolly Hospital, Dublin, and will take place from 2015 to 2019. In this study, there are two groups of patients. Both groups will perform an exercise program for 12 weeks. Physiotherapists will instruct them on how to perform the exercises. Each group will be given an ointment to place on the sore tendon using an applirule. This ointment will be applied daily for 6 months. One group will use an ointment containing nitroglycerin, the other group will use an ointment with no active ingredient. This is called a placebo. The patients will apply the ointment daily for 6 months.
The patients will be assessed at the start of the program and after 6, 12 and 24 weeks. Our main question is to see whether this exercise program when combined with a nitroglycerin ointment applied directly over the sore tendon can improve the outcomes and recovery time for people who suffer with Achilles tendon pain.
Read the detailed description
Study Design
The study will be designed to meet CONSORT guidelines. A randomized placebo controlled trial will be carried out at the Physiotherapy Department of Connolly Hospital, Blanchardstown, Dublin 15. The study will be conducted on patients who present to the department with a diagnosis of Achilles tendinopathy. The diagnosis will be confirmed based on a history of an insidious onset of Achilles tendon pain, a tender nodule/thickening of the tendon to the region 2 to 6cm from the calcaneal insertion, and an ultrasound examination that excludes a frank tear.
Participants will be randomly allocated to one of 2 groups. Group 1 will receive GTN for 24 weeks in combination with a supervised eccentric exercise programme delivered over 12 weeks. Group 2 will receive placebo GTN in addition to the same exercise programme.
Ethical Considerations Ethics approval will be sought from Connolly Hospital Research and Ethics Committee. All participants will give written informed consent.
At the patient's initial assessment, the following will be completed
- Outcome measure questionnaires - Victorian Institute of Sport Assessment-Achilles (VISA-A), Lower Extremity Functional Scale (LEFS), Numeric Rating Scale for pain (NRS)
- Assessment of Achilles tendon tenderness using pressure algometry
- Ultra-sound assessment of the Achilles tendon - tendon thickness measurements
- Proprioception testing (modified Star Excursion Balance Test)
- Simple strength tests of the Achilles, Hopping and heel raises
It is anticipated that the baseline assessment will take 60-75 minutes to complete. The follow-up assessment should take no more than 45 minutes to complete.
Outcome Measures All outcomes will be administered at baseline, and at week 6, 12 and 24 by the principal investigator. Data on adverse effects, compliance with the ointment application and the exercise program will be recorded at these scheduled visits.
Upon completion of the initial assessment by the principal investigator, participants will be scheduled to have their first exercise intervention session with one of the physiotherapists in Connolly Hospital. The treating physiotherapists will be trained in the exercise protocol and will be blinded to the type of GTN provided to the patient. This appointment will be scheduled within one week of the lead investigator's assessment. This tendon rehabilitation program is designed to encompass current methods of non-operative treatment of Achilles tendinopathy (Paoloni et al, 2004) and will involve the following:
- Instruction in performance of the Alfredson heavy load eccentric exercise program.
- Patients will be advised to avoid weight bearing sporting activities for the first 4 to 6 weeks, after which time gradual return to sports will be encouraged. Participation in sports will be continued so long as the pain does not increase above NRS>3 and no increase in Achilles morning stiffness is experienced.
- Instruction in the performance of daily static stretches of the gastrocnemius and soleus muscle groups
- Patients will be advised to avoid the use of co-interventions or complimentary treatments for the duration of the study.
Exercise interventions:
Participants will be instructed on how to perform the Alfredson heavy load eccentric exercise protocol (Alfredson, 1998) by the physiotherapists in Connolly Hospital. This will be performed during their first treatment session, which will take place approximately one week after the initial assessment. The participants will be given practical instructions and a written manual on the exercise program, which will include advice on progression of the exercise regimen.
Topical nitroglycerin ointment (GTN)
The topical GTN to be used for the purpose of this trial is Percutol. This will deliver the GTN in ointment form. Participants will be instructed in how to measure 0.5cm of Percutol ointment by applying 0.5cm of Percutol to a paper applicator/strip, which has the amount required indicated in a circular outline, measuring approximately the same size as a pea. This paper applicator/strip will be placed on a flat surface and the participant will squeeze the ointment onto the paper, carefully measuring the amount specified on the paper applicator. Participants will then place the paper on to the painful area of the Achilles with the ointment contacting the skin, and use the paper to lightly spread the ointment to cover the painful area of the Achilles tendon. The ointment should not be rubbed into the skin. The paper applicator will then be covered with surgical tape to hold the applicator in place. The participants will then replace the cap on the ointment and screw it on tightly and store it as per the instructions (at room temperature and out of reach and sight of children). Participants will be instructed to wash their hands before and after this process. The paper applicator with the Percutol ointment will be placed on the affected area of the Achilles tendon in the morning and left in situ for the daytime, and removed by the participant before sleeping at night. It will be emphasized that the ointment must be on while the participants perform the home exercise program (HEP).
0.5cm of Percutol has been chosen for the purpose of this trial. Aspire Pharma United Kingdom (UK) manufacture Percutol and have informed the PI that 1 inch of Percutol weighs 0.83g approximately and corresponds to 16.64mg of GTN.
The PI has conducted measures of Percutol, 0.5cm of Percutol weighs approximately 0.14 to 0.17g and this corresponds to 2.8 to 3.4mg of GTN.
The placebo to be used for the purpose of this trial will be aqueous cream and therefore will contain no GTN or active ingredient, which would assist in tendon healing. Participants will be instructed to apply the same amount of this placebo ointment in the exact same method as outlined for the GTN group using the same paper/applicator method.
Participants will be instructed in the use of the ointment during their initial visit with the lead investigator. They will be informed that the dosing regimen calls for the ointment to be applied to the painful area of the Achilles tendon and left in situ for 12 to 14 hours and removed at night prior to sleeping. This will then be discarded and replaced with a new measure of the ointment the next day. Participants will be advised to apply the ointment to the site of maximal tenderness within a region of 1-2 cm around this point. The participants will be advised to rotate the paper applicator about the site of maximal tenderness on a regular basis for the six-month duration of the study in an effort to minimize irritation of the skin.
- Conditions
- Tendinopathy, Achilles Tendon Pain
- Being tested
- glyceryl trinitrate, Placebo ointment, Eccentric exercise program
- Medical subject headings
- Tendinopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
glyceryl trinitrateDrug
Also called Percutol
Topical GTN will be used daily in combination with a eccentric home exercise program
Placebo ointmentOther
Also called aqueous cream
Topical placebo ointment will be used in combination with a eccentric home exercise program
Eccentric exercise programOther
Also called Alfredson's eccentric exercise program
All participants will complete the eccentric exercise program as a home exercise program daily.
| Study group | Role | What they receive |
|---|---|---|
| GTN and eccentric exercises | Active comparator | Participants will complete a 12 week eccentric exercise program and use 0.5cm of glyceryl trinitrate ointment daily for 24 weeks Receives: Drug: glyceryl trinitrate; Other: Eccentric exercise program |
| Placebo and eccentric exercises | Placebo comparator | Participants will use a placebo ointment with no active ingredient for 24 weeks and complete an eccentric exercise program for 12 weeks Receives: Other: Placebo ointment; Other: Eccentric exercise program |
What is being measured
The primary outcome is the main question the study is designed to answer.
VISA A, Victoria Institute of Sport Assessment - Achilles
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 (score 0 = worst, score 100 =perfect), 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).
Measured: Change from baseline in VISA A at week 6,12 and 24
Secondary outcomes (9)
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. It is easy to administer and score so is applicable for research purposes and clinical decision making for individual patients (Binkley et al., 1999).
Measured: Baseline and week 6, 12 and 24
Pain Detection Threshold, PDT using pressure algometry
The outcome measurement in pressure algometry is the pain detection threshold (PDT), measured in kg/f, 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.
Measured: baseline and week 6, 12 and 24
Ultra sound measure of Achilles thickness
Ultra sound will be used to measure any change in transverse thickness (measure in mm) of the achilles over the course of the trial
Measured: Baseline and week 6, 12 and 24
Numeric Rating Scale (NRS) for pain
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"
Measured: Baseline and week 6, 12 and 24
Star Excursion Balance Test (SEBT)
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 (appendix 3) has been shown to be a reliable measure of dynamic balance (Hertel et al, 2006).
Measured: baseline and week 6, 12 and 24
Heel raise for endurance
The heel raise test for endurance will be performed on one leg at a time with the participant standing. The participant will be allowed to have two fingers per hand, placed at shoulder height, against a wall for balance. 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.
Measured: Change in number of heel raises performed at baseline and week 6, 12 and 24
Heel raise for endurance
The heel raise test for endurance will be performed on one leg at a time with the participant standing. The participant will be allowed to have two fingers per hand, placed at shoulder height, against a wall for balance. 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.
Measured: Change in NRS with heel raises performed at baseline and week 6, 12 and 24
Hopping tests
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. A natural jump frequency is approximately 2 hops per second. 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 reliability in previous studies of Achilles tendinopathy (Silbernagel et al, 2001 and 2006).
Measured: Change in number of hops performed at baseline and weeks 6, 12 and 24
Hopping tests
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. A natural jump frequency is approximately 2 hops per second. 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 reliability in previous studies of Achilles tendinopathy (Silbernagel et al, 2001 and 2006).
Measured: Change in NRS associated with hopping performed at baseline and weeks 6, 12 and 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2015 (estimated)
- Study startSep 2016
- Primary completionNov 2018
- Study completionNov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for TendinopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal College of Surgeons, Ireland
- Sponsor type
- University, hospital or other
- Collaborators
- Health Research Board, Ireland
- Responsible party
- Sponsor
- Investigators
- Helen French, PhD, Study director, Royal College of Surgeons, IrelandTrevor Duffy, MD, MBA, Study director, Connolly Hospital, Dublin 15, Ireland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02499484
- Sponsor's protocol ID
- RCSI-1764
- Acronym
- NEAT
- Status last verified
- Apr 2018
- First submitted
- 7 Jul 2015
- Last updated
- 6 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Paoloni JA, Appleyard RC, Nelson J, Murrell GA. Topical glyceryl trinitrate treatment of chronic noninsertional achilles tendinopathy. A randomized, double-blind, placebo-controlled trial. J Bone Joint Surg Am. 2004 May;86(5):916-22. doi: 10.2106/00004623-200405000-00005.
PubMed 15118032Alfredson H, Pietila T, Jonsson P, Lorentzon R. Heavy-load eccentric calf muscle training for the treatment of chronic Achilles tendinosis. Am J Sports Med. 1998 May-Jun;26(3):360-6. doi: 10.1177/03635465980260030301.
PubMed 9617396Robinson JM, Cook JL, Purdam C, Visentini PJ, Ross J, Maffulli N, Taunton JE, Khan KM; Victorian Institute Of Sport Tendon Study Group. The VISA-A questionnaire: a valid and reliable index of the clinical severity of Achilles tendinopathy. Br J Sports Med. 2001 Oct;35(5):335-41. doi: 10.1136/bjsm.35.5.335.
PubMed 11579069Tumilty S, McDonough S, Hurley DA, Baxter GD. Clinical effectiveness of low-level laser therapy as an adjunct to eccentric exercise for the treatment of Achilles' tendinopathy: a randomized controlled trial. Arch Phys Med Rehabil. 2012 May;93(5):733-9. doi: 10.1016/j.apmr.2011.08.049.
PubMed 22541305Binkley JM, Stratford PW, Lott SA, Riddle DL. The Lower Extremity Functional Scale (LEFS): scale development, measurement properties, and clinical application. North American Orthopaedic Rehabilitation Research Network. Phys Ther. 1999 Apr;79(4):371-83.
PubMed 10201543Hertel J, Braham RA, Hale SA, Olmsted-Kramer LC. Simplifying the star excursion balance test: analyses of subjects with and without chronic ankle instability. J Orthop Sports Phys Ther. 2006 Mar;36(3):131-7. doi: 10.2519/jospt.2006.36.3.131.
PubMed 16596889Silbernagel KG, Gustavsson A, Thomee R, Karlsson J. Evaluation of lower leg function in patients with Achilles tendinopathy. Knee Surg Sports Traumatol Arthrosc. 2006 Nov;14(11):1207-17. doi: 10.1007/s00167-006-0150-6. Epub 2006 Jul 21.
PubMed 16858560Silbernagel KG, Thomee R, Thomee P, Karlsson J. Eccentric overload training for patients with chronic Achilles tendon pain--a randomised controlled study with reliability testing of the evaluation methods. Scand J Med Sci Sports. 2001 Aug;11(4):197-206. doi: 10.1034/j.1600-0838.2001.110402.x.
PubMed 11476424Williamson A, Hoggart B. Pain: a review of three commonly used pain rating scales. J Clin Nurs. 2005 Aug;14(7):798-804. doi: 10.1111/j.1365-2702.2005.01121.x.
PubMed 16000093
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of Topical Glyceryl Trinitrate (GTN) and Eccentric Exercises in the Treatment of Midportion Achilles Tendinopathy: a Randomized Placebo Controlled Trial
- ClinicalTrials.gov ID
- NCT02499484
- Acronym / sponsor ID
- NEAT / RCSI-1764
- Conditions
- Tendinopathy, Achilles Tendon Pain
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Royal College of Surgeons, IrelandUniversity, hospital or other
- Collaborators
- Health Research Board, Ireland
- Study start
- Sep 2016
- Primary completion
- Nov 2018 (actual)
- Study completion
- Nov 2018 (actual)
- First posted
- 16 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this research is to determine if the addition of topical GTN over 24 weeks to a 12 week exercise programme improves clinical outcomes more than placebo GTN for people with Achilles Tendinopathy.
Pain in the Achilles tendon is a common condition seen by physiotherapists and doctors. It affects people involved in sports and those who are not. It can limit the ability to walk, hop, jump and run. If the pain persists for longer than 3 months it can become extremely difficult to abolish. As a result, people with this common condition can suffer from prolonged pain and often the pain will persist and affect everyday activities.
While this is an easy injury to diagnose, it is not so easy to treat. Many treatments do exist, but often just provide short-term relief until the pain returns. Specific strengthening exercises have been shown to be beneficial in treating this condition.
The current project will study Achilles tendon pain in Irish adults at Connolly Hospital, Dublin, and will take place from 2015 to 2019. In this study, there are two groups of patients. Both groups will perform an exercise program for 12 weeks. Physiotherapists will instruct them on how to perform the exercises. Each group will be given an ointment to place on the sore tendon using an applirule. This ointment will be applied daily for 6 months. One group will use an ointment containing nitroglycerin, the other group will use an ointment with no active ingredient. This is called a placebo. The patients will apply the ointment daily for 6 months.
The patients will be assessed at the start of the program and after 6, 12 and 24 weeks. Our main question is to see whether this exercise program when combined with a nitroglycerin ointment applied directly over the sore tendon can improve the outcomes and recovery time for people who suffer with Achilles tendon pain.
Detailed description
Study Design
The study will be designed to meet CONSORT guidelines. A randomized placebo controlled trial will be carried out at the Physiotherapy Department of Connolly Hospital, Blanchardstown, Dublin 15. The study will be conducted on patients who present to the department with a diagnosis of Achilles tendinopathy. The diagnosis will be confirmed based on a history of an insidious onset of Achilles tendon pain, a tender nodule/thickening of the tendon to the region 2 to 6cm from the calcaneal insertion, and an ultrasound examination that excludes a frank tear.
Participants will be randomly allocated to one of 2 groups. Group 1 will receive GTN for 24 weeks in combination with a supervised eccentric exercise programme delivered over 12 weeks. Group 2 will receive placebo GTN in addition to the same exercise programme.
Ethical Considerations Ethics approval will be sought from Connolly Hospital Research and Ethics Committee. All participants will give written informed consent.
At the patient's initial assessment, the following will be completed
- Outcome measure questionnaires - Victorian Institute of Sport Assessment-Achilles (VISA-A), Lower Extremity Functional Scale (LEFS), Numeric Rating Scale for pain (NRS)
- Assessment of Achilles tendon tenderness using pressure algometry
- Ultra-sound assessment of the Achilles tendon - tendon thickness measurements
- Proprioception testing (modified Star Excursion Balance Test)
- Simple strength tests of the Achilles, Hopping and heel raises
It is anticipated that the baseline assessment will take 60-75 minutes to complete. The follow-up assessment should take no more than 45 minutes to complete.
Outcome Measures All outcomes will be administered at baseline, and at week 6, 12 and 24 by the principal investigator. Data on adverse effects, compliance with the ointment application and the exercise program will be recorded at these scheduled visits.
Upon completion of the initial assessment by the principal investigator, participants will be scheduled to have their first exercise intervention session with one of the physiotherapists in Connolly Hospital. The treating physiotherapists will be trained in the exercise protocol and will be blinded to the type of GTN provided to the patient. This appointment will be scheduled within one week of the lead investigator's assessment. This tendon rehabilitation program is designed to encompass current methods of non-operative treatment of Achilles tendinopathy (Paoloni et al, 2004) and will involve the following:
- Instruction in performance of the Alfredson heavy load eccentric exercise program.
- Patients will be advised to avoid weight bearing sporting activities for the first 4 to 6 weeks, after which time gradual return to sports will be encouraged. Participation in sports will be continued so long as the pain does not increase above NRS>3 and no increase in Achilles morning stiffness is experienced.
- Instruction in the performance of daily static stretches of the gastrocnemius and soleus muscle groups
- Patients will be advised to avoid the use of co-interventions or complimentary treatments for the duration of the study.
Exercise interventions:
Participants will be instructed on how to perform the Alfredson heavy load eccentric exercise protocol (Alfredson, 1998) by the physiotherapists in Connolly Hospital. This will be performed during their first treatment session, which will take place approximately one week after the initial assessment. The participants will be given practical instructions and a written manual on the exercise program, which will include advice on progression of the exercise regimen.
Topical nitroglycerin ointment (GTN)
The topical GTN to be used for the purpose of this trial is Percutol. This will deliver the GTN in ointment form. Participants will be instructed in how to measure 0.5cm of Percutol ointment by applying 0.5cm of Percutol to a paper applicator/strip, which has the amount required indicated in a circular outline, measuring approximately the same size as a pea. This paper applicator/strip will be placed on a flat surface and the participant will squeeze the ointment onto the paper, carefully measuring the amount specified on the paper applicator. Participants will then place the paper on to the painful area of the Achilles with the ointment contacting the skin, and use the paper to lightly spread the ointment to cover the painful area of the Achilles tendon. The ointment should not be rubbed into the skin. The paper applicator will then be covered with surgical tape to hold the applicator in place. The participants will then replace the cap on the ointment and screw it on tightly and store it as per the instructions (at room temperature and out of reach and sight of children). Participants will be instructed to wash their hands before and after this process. The paper applicator with the Percutol ointment will be placed on the affected area of the Achilles tendon in the morning and left in situ for the daytime, and removed by the participant before sleeping at night. It will be emphasized that the ointment must be on while the participants perform the home exercise program (HEP).
0.5cm of Percutol has been chosen for the purpose of this trial. Aspire Pharma United Kingdom (UK) manufacture Percutol and have informed the PI that 1 inch of Percutol weighs 0.83g approximately and corresponds to 16.64mg of GTN.
The PI has conducted measures of Percutol, 0.5cm of Percutol weighs approximately 0.14 to 0.17g and this corresponds to 2.8 to 3.4mg of GTN.
The placebo to be used for the purpose of this trial will be aqueous cream and therefore will contain no GTN or active ingredient, which would assist in tendon healing. Participants will be instructed to apply the same amount of this placebo ointment in the exact same method as outlined for the GTN group using the same paper/applicator method.
Participants will be instructed in the use of the ointment during their initial visit with the lead investigator. They will be informed that the dosing regimen calls for the ointment to be applied to the painful area of the Achilles tendon and left in situ for 12 to 14 hours and removed at night prior to sleeping. This will then be discarded and replaced with a new measure of the ointment the next day. Participants will be advised to apply the ointment to the site of maximal tenderness within a region of 1-2 cm around this point. The participants will be advised to rotate the paper applicator about the site of maximal tenderness on a regular basis for the six-month duration of the study in an effort to minimize irritation of the skin.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GTN and eccentric exercises | Active comparator | Drug: glyceryl trinitrate, Other: Eccentric exercise programParticipants will complete a 12 week eccentric exercise program and use 0.5cm of glyceryl trinitrate ointment daily for 24 weeks |
| Placebo and eccentric exercises | Placebo comparator | Other: Placebo ointment, Other: Eccentric exercise programParticipants will use a placebo ointment with no active ingredient for 24 weeks and complete an eccentric exercise program for 12 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Current diagnosis of Achilles tendinopathy
- Subjects must be able and willing to give written informed consent and to comply with the requirements of this study protocol
- Subjects must be male or female, aged 18 years or above at Baseline
- Achilles pain of >3 months or more
- Mid-portion Achilles tenderness and thickening on palpation
Key exclusion criteria (14 listed)
- Previous corticosteroid injection to the affected tendon in the past 3 months
- Symptoms of less than 3 months duration
- Previous use of topical GTN
- Current use of nitrates, eg: GTN spray, tablet, transdermal patch.
- Contra-indication to GTN therapy (see section 12.2.3)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| glyceryl trinitrateAlso: PercutolTopical GTN will be used daily in combination with a eccentric home exercise program | Drug | GTN and eccentric exercises |
| Placebo ointmentAlso: aqueous creamTopical placebo ointment will be used in combination with a eccentric home exercise program | Other | Placebo and eccentric exercises |
| Eccentric exercise programAlso: Alfredson's eccentric exercise programAll participants will complete the eccentric exercise program as a home exercise program daily. | Other | GTN and eccentric exercises, Placebo and eccentric exercises |
Primary outcome
VISA A, Victoria Institute of Sport Assessment - Achilles
Time frame: Change from baseline in VISA A at 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 (score 0 = worst, score 100 =perfect), 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).
9 secondary outcomes
Lower Extremity Functional Scale (LEFS)
Time frame: Baseline and week 6, 12 and 24
Pain Detection Threshold, PDT using pressure algometry
Time frame: baseline and week 6, 12 and 24
Ultra sound measure of Achilles thickness
Time frame: Baseline and week 6, 12 and 24
Numeric Rating Scale (NRS) for pain
Time frame: Baseline and week 6, 12 and 24
Star Excursion Balance Test (SEBT)
Time frame: baseline and week 6, 12 and 24
Heel raise for endurance
Time frame: Change in number of heel raises performed at baseline and week 6, 12 and 24
Heel raise for endurance
Time frame: Change in NRS with heel raises performed at baseline and week 6, 12 and 24
Hopping tests
Time frame: Change in number of hops performed at baseline and weeks 6, 12 and 24
Hopping tests
Time frame: Change in NRS associated with hopping performed at baseline and weeks 6, 12 and 24
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2019.
- Background: PubMed 15118032Paoloni JA, Appleyard RC, Nelson J, Murrell GA. Topical glyceryl trinitrate treatment of chronic noninsertional achilles tendinopathy. A randomized, double-blind, placebo-controlled trial. J Bone Joint Surg Am. 2004 May;86(5):916-22. doi: 10.2106/00004623-200405000-00005.
- Background: PubMed 9617396Alfredson H, Pietila T, Jonsson P, Lorentzon R. Heavy-load eccentric calf muscle training for the treatment of chronic Achilles tendinosis. Am J Sports Med. 1998 May-Jun;26(3):360-6. doi: 10.1177/03635465980260030301.
- Background: PubMed 11579069Robinson JM, Cook JL, Purdam C, Visentini PJ, Ross J, Maffulli N, Taunton JE, Khan KM; Victorian Institute Of Sport Tendon Study Group. The VISA-A questionnaire: a valid and reliable index of the clinical severity of Achilles tendinopathy. Br J Sports Med. 2001 Oct;35(5):335-41. doi: 10.1136/bjsm.35.5.335.
- Background: PubMed 22541305Tumilty S, McDonough S, Hurley DA, Baxter GD. Clinical effectiveness of low-level laser therapy as an adjunct to eccentric exercise for the treatment of Achilles' tendinopathy: a randomized controlled trial. Arch Phys Med Rehabil. 2012 May;93(5):733-9. doi: 10.1016/j.apmr.2011.08.049.
- Background: PubMed 10201543Binkley JM, Stratford PW, Lott SA, Riddle DL. The Lower Extremity Functional Scale (LEFS): scale development, measurement properties, and clinical application. North American Orthopaedic Rehabilitation Research Network. Phys Ther. 1999 Apr;79(4):371-83.
- Background: PubMed 16596889Hertel J, Braham RA, Hale SA, Olmsted-Kramer LC. Simplifying the star excursion balance test: analyses of subjects with and without chronic ankle instability. J Orthop Sports Phys Ther. 2006 Mar;36(3):131-7. doi: 10.2519/jospt.2006.36.3.131.
- Background: PubMed 16858560Silbernagel KG, Gustavsson A, Thomee R, Karlsson J. Evaluation of lower leg function in patients with Achilles tendinopathy. Knee Surg Sports Traumatol Arthrosc. 2006 Nov;14(11):1207-17. doi: 10.1007/s00167-006-0150-6. Epub 2006 Jul 21.
- Background: PubMed 11476424Silbernagel KG, Thomee R, Thomee P, Karlsson J. Eccentric overload training for patients with chronic Achilles tendon pain--a randomised controlled study with reliability testing of the evaluation methods. Scand J Med Sci Sports. 2001 Aug;11(4):197-206. doi: 10.1034/j.1600-0838.2001.110402.x.
- Background: PubMed 16000093Williamson A, Hoggart B. Pain: a review of three commonly used pain rating scales. J Clin Nurs. 2005 Aug;14(7):798-804. doi: 10.1111/j.1365-2702.2005.01121.x.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Helen French, PhD study director
Royal College of Surgeons, Ireland
Trevor Duffy, MD, MBA study director
Connolly Hospital, Dublin 15, Ireland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing glyceryl trinitrate and Eccentric exercise program in people with Tendinopathy and Achilles Tendon Pain, run by Royal College of Surgeons, Ireland at 1 site in Ireland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
VISA A, Victoria Institute of Sport Assessment - Achilles (time frame: Change from baseline in VISA A at week 6,12 and 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02499484, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2019.