The Soft Tissue Injection of Corticosteroid And Local Anaesthetic Study - A Single Site, Non-inferiority Randomised Control Trial Evaluating Pain After Soft Tissue Corticosteroid Injections With and Without Local Anaesthetic
Phase: PHASE3
Conditions: Carpal Tunnel Syndrome, De Quervains Tenosynovitis, Trigger Finger
Sponsor: University Hospital Plymouth NHS Trust

IRAS 259336 
 
 
 
 
Study: The SToICAL Study 
 
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The SToICAL Study 
 
The Soft Tissue Injection of Corticosteroid And Local anaesthetic Study – A single site, non-inferiority 
randomised control trial evaluating pain after soft tissue corticosteroid injections with and without local 
anaesthetic 
 
 
 
 
 
Version 2 (Final), 7 Jan 2020 
 
 
 
 
 
 
 
SPONSOR: University Hospitals Plymouth NHS Trust (UHPNT)   
REC REFERENCE: <Insert> 
IRAS No: 259336 
 
 
 
Protocol authorised by: 
 
Name & Role 
Date 
Signature 
Charles Gozzard (Consultant)  
Chief Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Study Management Group 
 
Chief Investigator:  
Mr C Gozzard 
Trauma and Orthopaedic Department  
Level 11 
Derriford Hospital  
PL6 8DH 
charlesgozzard@nhs.net  
 
Principle Investigator: 
Mr M Jones 
Trauma and Orthopaedic Department  
Level 11 
Derriford Hospital  
PL6 8DH 
m.jones16@nhs.net 
 
Co-investigators:  
Miss S Fullilove 
Trauma and Orthopaedic Department  
Level 11 
Derriford Hospital  
PL6 8DH 
sue.fullilove@nhs.net  
 
Dr E Doyle 
Trauma and Orthopaedic Department  
Level 11 
Derriford Hospital  
PL6 8DH 
edoyle@nhs.net  
 
Mr Jonathan Evans 
NIHR Clinical Lecturer - University of Exeter  
St Lukes Campus  
79 Heavitree Road  
Exeter  
EX1 1TX 
jonathanevans2@nhs.net 
 
 
Clinical Queries 
 
Clinical queries should be directed to Mr C Gozzard who will direct the query to the appropriate 
person. 
 
 
 
 
 
 

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Sponsor 
 
University Hospitals Plymouth NHS Trust is the main research sponsor for this study.  For further 
information regarding the sponsorship conditions, please contact the Research Manager at: 
 
 
 
Research Development and Innovation 
University Hospitals Plymouth NHS Trust 
Level 2 MSCP  
Bircham Park Offices 
1 Roscoff Rise 
Derriford  
Plymouth 
PL6 5FP 
 
Tel 01752 432842 
 
Funder 
 
This study will be funded by available Departmental research funds. Depending on the study cost 
analysis review further external funds may have to be sought.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
This protocol describes the study and provides information about procedures for entering participants.  Every care 
was taken in its drafting, but corrections or amendments may be necessary. These will be circulated to investigators 
in the study.  Problems relating to this study should be referred, in the first instance, to the Chief Investigator.  
This study will adhere to the principles outlined in the NHS UK Policy Framework for Health and Social Care 
Research (2017).  It will be conducted in compliance with the protocol, the Data Protection Act and other regulatory 
requirements as appropriate.  
 

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Table of Contents 
1. 
INTRODUCTION 
7 
1.1 
BACKGROUND 
7 
1.2 
RATIONALE FOR CURRENT STUDY 
9 
1.3 
PATIENT AND PUBLIC INVOLVEMENT 
10 
2.  STUDY OBJECTIVES 
10 
3.  STUDY DESIGN 
11 
3.1 
STUDY OUTCOME MEASURES 
15 
4. 
PARTICIPANT ENTRY 
15 
4.1 
RECRUITMENT 
15 
4.2 
PRE-REGISTRATION EVALUATIONS 
16 
4.3 
INCLUSION CRITERIA 
16 
4.4 
EXCLUSION CRITERIA 
16 
4.5 
WITHDRAWAL CRITERIA 
16 
5. 
ADVERSE EVENTS 
16 
5.1 
DEFINITIONS 
16 
5.2 
REPORTING PROCEDURES 
17 
5.3 
RESPONSIBILITIES 
18 
6. 
ASSESSMENT AND FOLLOW-UP 
19 
7. 
STATISTICS AND DATA ANALYSIS 
19 
7.1 
DESCRIPTION OF STATISTICAL METHODS 
19 
7.2 
THE NUMBER OF PARTICIPANTS 
20 
7.3 
THE LEVEL OF STATISTICAL SIGNIFICANCE 
20 
7.4 
CRITERIA FOR THE TERMINATION OF THE TRIAL. 
21 
7.5 
PROCEDURE FOR ACCOUNTING FOR MISSING, UNUSED, AND SPURIOUS DATA. 
21 
7.6 
INCLUSION IN ANALYSIS 
21 
8. 
ARCHIVING 
21 
9. 
REGULATORY ISSUES 
21 
9.2 
CONSENT 
22 
9.3 
CONFIDENTIALITY 
22 
9.4 
INDEMNITY 
22 
9.5 
SPONSOR 
22 
9.6 
FUNDING 
22 
9.7 
MONITORING 
22 
10. 
STUDY MANAGEMENT 
23 
11. 
PUBLICATION POLICY 
23 
12. 
REFERENCES 
23 
 
 

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GLOSSARY OF ABBREVIATIONS 
AE 
Adverse event 
AR 
Adverse reaction 
CI 
Chief Investigator 
CRF 
Case Report Form 
CT 
Clinical Trials 
DMC 
Data Monitoring Committee 
GCP 
Good Clinical Practice 
GP 
General Practitioner 
ICF 
Informed Consent Form 
ICH 
International Conference of Harmonisation 
NHS 
National Health Service 
NRES 
National Research Ethics Service 
PI 
Principal Investigator 
PIS 
Participant/ Patient Information Sheet 
R&D 
NHS Trust R&D Department 
REC 
Research Ethics Committee 
SAE 
Serious Adverse Event 
SAR 
Serious Adverse Reaction 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
SmPC/SPC 
Summary of Products Characteristics 
SOP 
Standard Operating Procedure 
TMF 
Trial Master File 
TSG 
Trials Steering Group 
 
 
 
KEYWORDS 
Corticosteroid 
Local anaesthetic  
Trigger finger  
De Quervains tenosynovitis  
Carpal tunnel syndrome 
 
 
 

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STUDY SUMMARY 
 
TITLE 
The SToICAL Study: The Soft Tissue Injection of Corticosteroid And Local anaesthetic 
Study – A single site non-inferiority randomised control trial evaluating pain after soft 
tissue corticosteroid injections with and without local anaesthetic 
DESIGN 
A single site, patient and assessor blinded, non-inferiority randomised control trial of 
patients with a clinical diagnosis of trigger finger, de Quervains tenosynovitis or carpal 
tunnel syndrome, treated with a corticosteroid injection co-administered with or without 
local anaesthetic.  
AIMS 
To determine whether pain experienced during the 24 hours after a corticosteroid 
injection to the hand and wrist is no worse than (not inferior to) the pain experienced after 
a corticosteroid and local anaesthetic injection.  
OUTCOME 
MEASURES 
The primary objective;  
Investigate whether there is a difference in pain VAS scores at 1-hour after a 
corticosteroid injection for trigger finger, de Quervains tenosynovitis or carpal tunnel 
syndrome co-administered with or without local anaesthetic.  
 
The secondary objectives; 
i) Investigate whether there is a difference in pain VAS scores during the 24-hours after 
a corticosteroid injection for trigger finger, de Quervains tenosynovitis or carpal tunnel 
syndrome co-administered with or without local anaesthetic.  
 
ii) Investigate whether there is a difference in the pain VAS scores at the time of the 
corticosteroid injection for trigger finger, de Quervains tenosynovitis or carpal tunnel 
syndrome co-administered with or without local anaesthetic. 
 
iii) Investigate the difference in the additional analgesia required and in the functional use 
of the hand during the first 3 hours following a corticosteroid injection for trigger finger, de 
Quervains tenosynovitis or carpal tunnel syndrome co-administered with or without local 
anaesthetic.  
 
These outcomes will be determined by assessing patients’ pain using a 100mm VAS 
score before and at time of the injection, and at 5-minutes, 1-hour, 2-hours, 3-hours and 
24-hours after the injection. This will be supplemented by questions to determine whether 
additional analgesia was required and if there was any effect on hand function following 
the injection. No subgroup analysis will be performed.  
POPULATION 
Patients attending elective hand and wrist outpatient clinics at the University Hospitals 
Plymouth NHS Trust with a clinical diagnosis of trigger finger, de Quervains and carpal 
tunnel syndrome. 
ELIGIBILITY 
All patients over the age 18 years old with a clinical diagnosis of trigger finger, de 
Quervains tenosynvitis or carpal tunnel syndrome and who are able to give written 
informed consent for treatment will be included. Patients will be excluded if they have had 
previous surgery or corticosteroid injection for the condition being treated at the site 
considered for injection. A previous corticosteroid injection elsewhere in the hand does 
not exclude a patient from the trial. Those who are pregnant, breast-feeding or who have 
a history of hypersensitivity to corticosteroid or local anaesthetic will be excluded.  
DURATION 
The study will run for a 12-month period or until 100 patients have been recruited to the 
trial.  
 
 

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1. 
INTRODUCTION  
 
1.1 
BACKGROUND 
Corticosteroid injections are used in the treatment of a variety of hand and wrist conditions. They have 
local anti-inflammatory effects from blocking cytokine production involved in the inflammation process1.  
The injections can be administered intra or extra-articularly, with or without image guidance and with or 
without local anaesthetic. The co-administration of a local anaesthetic and corticosteroid aims to reduce 
pain soon after the injection. However no studies have directly compared this with using corticosteroid 
alone, to determine whether there is a difference in patients pain. 
 
Conditions: 
Trigger finger, de Quervains tenosynovitis and carpal tunnel syndrome are painful conditions of the hand 
and wrist where corticosteroid injections have a role in their treatment.  
 
Trigger finger is a condition that causes locking on flexion of the involved finger, dysfunction and pain 
as a result of thickening of the first annular pulley, which affects 2% of the general population2, 3. 
Available treatments are operative (A1 pulley release) and non-operative (corticosteroid injection and 
splinting). Operative treatment has an effective cure rate of 89-97% with increased costs, longer 
absence from work, and the possibility of surgical complications4. Corticosteroid injection is an effective 
and safe treatment with cure rates ranging from 60-92%3.  
 
De Quervains tenosynovitis is a disorder that causes radial sided wrist pain as a result of mechanical 
impingement of the tendons within the first extensor compartment5. The prevalence of de Quervains 
tenosynovitis in the United Kingdom is 0.5% in men and 1.3% in women6. Available treatments are 
operative (slitting or removing a strip of the tendon sheath) and non-operative (corticosteroid injection 
and splinting). Operative treatment has an effect cure rate of 91%, but is more invasive and associated 
with higher costs and the possibility of surgical complications7. Corticosteroid injections have cure rate 
of 83% and is a superior treatment compared to splinting8.  
 
Carpal tunnel syndrome causes pain and numbness in a median nerve distribution in the hand from 
compression of the nerve within the carpal tunnel, and affects 3.8% of the general population9, 10. 
Available treatments are operative (Carpal tunnel decompression) and non-operative (corticosteroid 
injection and wrist splinting). Surgery is preferred in severe cases whereas in mild and moderate case 
non-surgery treatments are used initially11.  
 
Administration: 
Corticosteroid injections administered into soft tissue for these conditions can be performed under 
ultrasound guidance or by using anatomical landmarks. Landmark guided injections can be performed 
at the time of consultation within the outpatient clinic without additional imaging. Ultrasound guided 
injections are performed by the radiology department with variable on-the-day availability. Often a 
separate outpatient appointment is required to deliver this treatment. The accuracy and effectiveness of 
both methods of delivery have been studied.  
 
A cadaveric study showed no statistical difference in the accuracy between ultrasound and landmark 
guided injections for de Quervains tenosynovitis or carpal tunnel syndrome. The incidence of success 
without ultrasound guidance was 95% and 100% for de Quervains tenosynovitis and carpal tunnel 
syndrome respectively; injections for trigger finger were not included12. Despite both ultrasound and 
landmark guided injections being effective in reducing symptoms and improving hand function in carpal 
tunnel syndrome, ultrasound guided injections have shown superior clinical outcomes13,14.  
 
Although no clinical study directly compared ultrasound versus landmark guided corticosteroid injections 
for de Quervains tenosynovitis, there is evidence suggesting that ultrasound guidance has a slightly 

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better clinical outcome. A pooled quantitative literature evaluation of landmark-guided injections showed 
a complete resolution of symptoms in 83% of patients, compared to 92% in a study using ultrasound 
guidance8,15. A prospective randomised trial showed no superior clinical benefit in administering 
corticosteroid injections for trigger finger with ultrasound guidance, and noted the extra time and effort 
required16. There is also no benefit to injecting the corticosteroid into the tendon sheath versus outside 
the sheath17.  
 
Landmark guided corticosteroid injections for trigger finger, de Quervains tenosynovitis and carpal 
tunnel syndrome are performed routinely in clinical practice across the National Health Service (NHS). 
Evidence supports the efficacy for landmark guided injections, although in some conditions the use of 
ultrasound can slightly improve clinical outcomes. However, nowhere considers the additional costs, the 
delay in treatment and the patient experience benefits of receiving an on-the-day clinic based treatment.  
 
The number of corticosteroid injections given at University Hospitals Plymouth NHS Trust in the elective 
hand and wrist clinic was determined using clinical codes. 25 patients over a 6-month period were coded 
to have had a corticosteroid injection. It is likely the coding system is not accurately capturing all 
corticosteroid injections performed. Anecdotally it is felt that 3-5 corticosteroid injections are performed 
each week. In light of this, a three week prospective audit was conducted during which 11 corticosteroid 
injections were performed, which is an average of 3.6 per week.  
 
Corticosteroid injections: 
There are a variety of injectable synthetic corticosteroids with different half-lives and variable duration 
of clinical benefit even between individuals with the same corticosteroid18. Triamcinolone (40mg/1ml) is 
used routinely for soft tissue corticosteroid injections of the hand and wrist at University Hospitals 
Plymouth NHS Trust by the local Hand and Wrist surgeons.  
 
There are a number of possible adverse effects with corticosteroid injections, which include; local 
infection, skin atrophy, skin depigmentation, fat necrosis and allergic reactions19. It can increase blood 
glucose level in diabetic patients for up to 5 days, although a study of extra-articular injections in the 
hand and wrist showed that this was not clinically significant20. The National Institute for Clinical 
Excellence (NICE) recommends that caution be used if the patient is taking oral anti-coagulation21, but 
it is not a contra-indication. Another possible adverse effect is a post injection flare, which is a local 
increase in inflammation that develops within hours and can last 2-3 days22. The post injection flare has 
been described in intra-articular injections to begin after 90 minutes, last for less than 24 hours and be 
as a result of a crystal-induced synovitis23. It may then be 3 to 7 days before the corticosteroid becomes 
effective24.  
 
The Cochrane reviews for corticosteroid injection in trigger finger and de Quervains reported no adverse 
events2, 5. A review of over 9000 corticosteroid injections for carpal tunnel syndrome found; severe side 
effects in <0.1%(tendon rupture, intraneural injection, gangrene), minor persistent local effects in 2%, 
(subcutaneous atrophy, depigmentation) and transient effects in 15-20% (pain, bruising, facial 
flushing)25.  
 
Local anaesthetic: 
Corticosteroids are often mixed with local anaesthetic and co-administered to reduce pain after the 
injection. 1ml of 1% lidocaine is often mixed with 1ml Triamcinolone (40mg/1ml) as part of routine 
practice for soft tissue corticosteroid injections in the hand and wrist at University Hospital NHS Trust 
by the local Hand and Wrist surgeons. The mixing does not create a greater propensity for corticosteroid 
crystals to aggregate or change size; therefore they are safe to co-administer26.  
 
Lidocaine is a local anaesthetic with a rapid onset of less than 2 minutes and its effects can last for 1 to 
3 hours, and has a maximum dose of 5mg/kg27. Lidocaine works by blocking voltage gated sodium 
channels in neuronal cell membranes preventing the propagation of action potentials. The British 

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National Formulary advises that local anaesthetic should not be injected into inflamed or infected 
tissues28. 
 
An injection containing lidocaine can be painful because of the acidity of the solution, which can be 
neutralised with sodium bicarbonate. However, a randomised control trial failed to demonstrate a 
statistically significant benefit of sodium bicarbonate in extra-articular corticosteroid injections with local 
anaesthetic in the hand and wrist22.  
 
Assessment of pain: 
Pain is subjective and multi-dimensional therefore it is difficult to fully evaluate the complete pain 
experience. The 100mm visual analogue scale (VAS) score is a widely used method for assessing pain. 
It is generally accepted that a pain VAS score of 30, 70 and 100 indicates the upper boundaries of mild, 
moderate and severe pain intensity29.  
 
A reduction in pain score does not directly correlate with an improvement in a patients’ experience of 
that pain. Minimally clinically important difference (MCID) is what minimal change in a pain VAS score 
would indicate a real change in a patients’ pain intensity. A systematic review of 29 studies identified an 
absolute MCID ranging from 8mm to 40mm and could not conclude a single MCID value because of the 
variety of different methods used to calculate the MCID. The importance of making a comparison against 
a patients’ baseline pain was recognised30. 
 
The authors are not aware of any studies that have evaluated the MCID in pain VAS score following soft 
tissue corticosteroid injection in the hand and wrist. A recent observational study assessed MCID in VAS 
score in 224 post-operative patients concluded a MCID in pain VAS score of 10mm31. Two different 
papers determine 14mm as the MCID in pain VAS score in treatment of rotator cuff disease and following 
shoulder arthroplasty32, 33.  A large prospective multicentre study determined the MCID in pain VAS 
score in those with knee osteoarthritis to be 19.9mm34. This study was reference and a MCID of 20mm 
used to evaluate patient reported outcomes following arthroplasty surgery35. A 20mm MCID has also 
been used in other studies evaluating post procedural pain36, one of which was also investigating pain 
following soft tissue corticosteroid injections in the hand22. Therefore, for the purpose of this study a 
MCID of 20mm will be used. 
 
Non-inferiority studies: 
Non-inferiority studies are a one-sided test used to determine if a novel treatment is no worse than the 
standard treatment. It is designed to show that the novel treatment is no less than a pre-specified un-
important amount from the standard intervention. Equivalence studies are a two-sided test used to show 
a novel treatment is no worse or no better than the standard treatment. It is designed to show that the 
two treatments do not differ in either direction by more than a pre-specified unimportant amount. This 
pre-specific unimportant amount is the margin that defines the “zone of indifference” within which the 
interventions are considered equivalent or non-inferior. Non-inferiority studies are often used in 
therapeutic trials when a novel treatment offers additional benefits to the standard treatment and the 
aim is to show that is non-inferior37,38.   
 
In this instance the standard treatment is considered as a corticosteroid co-administered with local 
anaesthetic and the novel treatment corticosteroid alone. The hypothesis is that the pain at 1-hour post 
injection of corticosteroid alone is no worse than (not inferior to) the pain following a corticosteroid 
injection co-administered with local anaesthetic. The benefits of injecting corticosteroid alone, if the post 
injection pain was not inferior to co-administering it with local anaesthetic includes; stopping 
unnecessary administration of medication and reducing treatment time and cost. The zone of 
indifference has been set at <20mm, which has been determined from a MCID of 20mm a value below 
which it has been shown that there is no difference in pain experienced by the patient.  
 
1.2 
RATIONALE FOR CURRENT STUDY 

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The authors are not aware that a study exists that assesses pain following soft tissue corticosteroid 
injections in the hand and wrist, co-administered with and without local anaesthetic. Although, 
corticosteroids and local anaesthetic are often co-administered no evidence is currently available to 
support this.  
 
The effects of the local anaesthetic only last for 2-3 hours; therefore it would not provide relief from post-
procedure flares nor bridge the time until the corticosteroid becomes effective. Administering local 
anaesthetic can be painful because of the acidity of the solution and means higher volume injections 
are given. The use of local anaesthetic may also worsen paraesthesia symptoms or result in 
paraesthesia in parts of the hand, preventing normal function for the duration of its action.  
 
Adding local anaesthetic increases the cost, time and clinical waste of the treatment. Although, the 
additional cost per treatment may not be significant when considering the number performed across the 
National Health Service, the saving may be considerable.  
 
We hypothesise, that the pain experienced at 1-hour after a corticosteroid injection for trigger finger, de 
Quervains tenosynovitis and carpal tunnel syndrome is no worse than when the corticosteroid is co-
administered with local anaesthetic.  
 
1.3 
PATIENT AND PUBLIC INVOLVEMENT 
This study proposal was discussed with a number of patients within the hand clinic. To collect objective 
evidence a patient opinion questionnaire was developed.  
 
13 patients completed this questionnaire of which 10 had had previous corticosteroid injections (9 for 
trigger finger and 1 for carpal tunnel syndrome). 7 were given the injection with local anaesthetic, 1 
without local aesthetic and 1 did not know if local anaesthetic was used or not. All 13 patients indicated 
that they would be able to complete and return the proposed patient assessment form and if asked 
would agree to be randomised into this study.  
 
When asked about their thoughts about being include in a study like this, patients responded:  
“Not a problem”  
“I would be willing to help the study” 
“Great study as could be wasting money” 
“No problem whatsoever” 
“I’ll be happy if it can help doctors with patients’ treatment” 
 
When asked what would put them off about being included the majority said “nothing”, however 2 
patients who had had injections before were reluctant to have further injections because they were 
painful and not well tolerated.  
 
2.  STUDY OBJECTIVES 
The primary objective;  
Investigate whether there is a difference in pain VAS scores at 1-hour after a corticosteroid injection for 
trigger finger, de Quervains tenosynovitis or carpal tunnel syndrome co-administered with or without 
local anaesthetic.  
 
The secondary objectives; 
i) Investigate whether there is a difference in pain VAS scores during the 24-hours after a corticosteroid 
injection for trigger finger, de Quervains tenosynovitis or carpal tunnel syndrome co-administered with 
or without local anaesthetic.  
 

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ii) Investigate whether there is a difference in the pain VAS scores at the time of the corticosteroid 
injection for trigger finger, de Quervains tenosynovitis or carpal tunnel syndrome co-administered with 
or without local anaesthetic. 
 
iii) Investigate the difference in the additional analgesia required and in the functional use of the hand 
during the first 3 hours following a corticosteroid injection for trigger finger, de Quervains tenosynovitis 
or carpal tunnel syndrome co-administered with or without local anaesthetic.  
 
3.  STUDY DESIGN 
This is a single site, patient and assessor blinded, non-inferiority randomised control trial where patients 
will be randomised to receive an injection of corticosteroid alone or an injection of corticosteroid co-
administered with local anaesthetic to treat; trigger finger, de Quervains tenosynovitis or carpal tunnel 
syndrome.  
 
The reviewing physician will identify eligible patients during 20-minute outpatient hand and wrist clinic 
appointments. Providing that the patient meets the inclusion and exclusion criteria the supernumerary 
registrar in clinic will explain the study to the patient and provide them with an information leaflet 
(Appendix 1). Patients considering enrolment will return to the waiting room to read the study 
information. This allows sufficient time for the patients to go through the information at their own pace 
and for the clinic to continue to avoid it running behind. The patients can have the duration of the morning 
clinic (if required) to consider enrolment in the study. After the patients have read the study information 
they will return to clinic as soon as they are ready and be seen by the registrar a separate clinic room. 
There will be no pressure to participate and if patients do not want to be included they will still receive 
treatment within the clinic, as they would do normally. 
 
Normal practice for patients attending outpatient hand and wrist clinic with a clinical diagnosis of trigger 
finger, de Quervains tenosynovitis or carpal tunnel syndrome: 
 
 
 
Once the patient feels well informed and comfortable to participate, consent will be received (Appendix 
2) and a patient participation record completed (Appendix 3). A photocopy of the consent form will be 
given to the patient and another copy kept in the patients’ hospital notes. The original consent form will 
be kept in the site file along with the patients’ participation record. The patient participation record 
contains a patient participation number, which is the only link between the patient and the treatment 
Patients attend outpatient clinic 
Patients seen in a 20-minute clinic 
appointment  
During the appointment:  

- Clinical diagnosis made  

- Treatment options discussed 

- If appropriate, steroid injection offered 
and administered 
3 week Outpatient/ telephone clinic follow-up 

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delivered. The supernumerary registrar uses a computerised randomisation system to randomise the 
patient into one of the two treatment arms, whilst the patient completes the pre-injection validated pain 
VAS score on the patient assessment record (Appendix 4).  
 
Patients will be randomised using the simple randomisation service provided by Sealed Envelope Ltd.  
This is an online service that provides random permuted block randomisation, ensuring participants are 
balanced between the control and treatment group. The physician will use a unique URL and password 
to randomise patients in A (treatment) or B (control) group.  
 
Patients will receive injections containing one of the two following solutions, delivered under landmarks 
guidance to treat either; trigger finger, de Quervains tenosynovitis or carpal tunnel. Both combinations 
are used as part of routine practice for soft tissue corticosteroid injections in the hand and wrist at 
University Hospital NHS Trust by the local Hand and Wrist surgeons:  
A. 1ml of triamcinolone (40mg/1ml)  
or 
B. 1ml of triamcinolone (40mg/1ml) + 1ml 1% Lidocaine 
 
The registrar will draw up, prepare the treatment in a separate room so that the patient will remain 
blinded. Neither treatment can be distinguished from one another by their appearance alone.  
 
During the clinic appointment the patient will complete a pain VAS score prior to the injection, for pain 
experience at the time of the injection and at 5 minutes post injection on the patient assessment record. 
The pain VAS score of the pain experience during the corticosteroid steroid will be recorded immediately 
after the procedure.  The patient then takes the patient assessment record home to complete further 
pain VAS scores at; 1-hour, 2-hour, 3-hour and 24-hours following the injection. The timings at which 
these scores must be recorded will be clearly documented on the patient assessment record by the 
physician before leaving clinic to help remind the patient. There are three further questions, on the same 
form; that the patient will be required to answer at 3-hours post injection (Appendix 4).  
 
During the first 3-hours after your steroid injection: 
1. Did you take any additional painkillers because of pain at the injection site? 
YES 
☐ 
Medication:  
 
 
Time taken:   
 
NO  
☐ (go to next question) 
 
 
2. Did you have any reduction in hand function, below normal, as a result of the injection? 
YES 
☐, please describe your reduction in function: 
 
 
NO 
☐ 
 
3. Did you experience any new numbness in your hand, as a result of the injection? 
YES 
☐ 
 
NO 
☐ 
 
 
After the final pain VAS score at 24-hours the patient will receive a follow-up call by the registrar to 
ensure the assessment form has been completed, to answer any questions and remind the patient to 

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return the form using the prepaid envelope provided. After the form is posted the patients participation 
in the study will be complete. 
 
The routine dictated clinic letter completed by the physician will outline the patients diagnosis, inclusion 
into the trial, and an overview of the trial and the consent process, but will not specify which treatment 
was delivered. A copy of this letter is kept in the patients’ notes and a copy is sent to the GP.  
 
The patient participation record and a copy of the consent form will be kept in the site file and stored in 
a locked filling cabinet in Mr Gozzard’s Office, Level 11, Derriford Hospital.  
 
Returned patient assessment records will be collected by the departmental secretary, held within the 
site file and remain sealed until the end of recruitment. Once the recruitment phase is completed the 
patient assessment records will be open and the pain VAS scores will be measured, recorded on an 
excel spread sheet then statistically analysed by a blinded assessor (Mr M Jones - A member of the 
study management team, but directly not involved in patient recruitment). The same individual, who will 
not be involved in patient recruitment, will take all the measurements. Measurements will be taken using 
a standard 20cm ruler with 1mm increments and recorded to the nearest. Incomplete patient 
assessment records will be included on an intention to treat basis. A summary of the investigations, 
treatment and assessment can be found in Appendix 5. A planned time for the SToICAL study is outline 
in a Chart (Appendix 6) 
 
 
 

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Patient recruitment process during outpatient clinic:  
 
Patient returns to the waiting 
room to read the study 
information 
Patient seen by the registrar 
in a separate clinic room and 
any study questions 
answered 
Computer randomisation 
completed by the registrar 
Registrar prepares the steroid 
injection, whilst patient remains 
blinded  
Patient completes the pre-
injection pain VAS score 
Patient signs consent form 
(copies for the patient and the 
patient notes) and the registrar 
completes patient participation 
form
Patient completes the pain VAS 
score for the injection itself 
Patient remains in the clinic to 
complete the 5-minute post 
injection VAS pain score 
Patient leaves clinic and 
required to complete further 
pain VAS scores at: 1, 2, 3 and 
24 hours post injection 
24-hour follow-up phone 
call by the registrar  
Patient returns assessment 
form 
Patients’ involvement in the 
study is complete 
3-week follow-up 
outpatient/ telephone clinic 
appointment 
Patients attend outpatient 
clinic 
Patients seen in a 20-minute 
clinic appointment  
During appointment:  
- Clinical diagnosis made  
- Treatment options 
discussed 
- If eligible, inclusion into the 
trial discussed 
- Patient information provide 
- Treatment options 
discussed 
- If appropriate, steroid 
injection offered and 
administered as per normal 
practice 
3 week Outpatient/ 
telephone clinic follow-up 
Patient is not 
enrolled in 
study 
Patient 
enrolled in 
study 
Steroid injection administered 
by registrar 

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3.1 
STUDY OUTCOME MEASURES 
Patients pain will be measured using a 100mm pain VAS score which they will complete on a paper 
form; before the injection, at the time of injection, then 5-minutes, 1-hour, 2-hours, 3-hours and 24-hours 
after the injection. Patients will remain active in the study until the final VAS score is completed and the 
form is returned.  
 
Assessment of additional analgesia required and any reduction in hand function will be determined by 
the patients answers to the following three question, which are completed 3-hours after the injection 
(Appendix 5). 
 
During the first 3-hours after your steroid injection: 
1. Did you take any additional painkillers because of pain at the injection site? 
YES 
☐ 
Medication:  
 
 
Time taken:   
 
NO  
☐ (go to next question) 
 
 
2. Did you have any reduction in hand function, below normal, as a result of the injection? 
YES 
☐, please describe your reduction in function: 
 
 
NO 
☐ 
 
3. Did you experience any new numbness in your hand, as a result of the injection? 
YES 
☐ 
 
NO 
☐ 
 
The study will end once 100 patients have been recruited, which includes 82 patients to achieve 95% 
power, plus 20% to account for potential dropouts. With an average of 3.6 corticosteroid injections given 
every week and an estimated 60% capture rate, full recruitment should be achievable within 12 months.  
 
4. 
PARTICIPANT ENTRY 
 
4.1 
RECRUITMENT 
The reviewing physician will approach potentially eligible patients for the study during a clinic they are 
routinely attending after determining whether they meet the inclusion /exclusion criteria.  All patients will 
be spoken to in person during their clinic appointment. Potential participants will have the duration of 
the morning clinic to decide whether or not to participate in the study. It is standard practice to offer and 
deliver a corticosteroid injection within a 20 minutes clinic appointment, without pre-warning that this 
may be appropriate or available within clinic. Patients rarely need additional time to decide if they would 
like this on the day treatment.  
A verbal explanation of the trial and why the patient has been invited to participate will be given, together 
with a Participant Information Sheet (Appendix 2) and a copy of the Patient Consent Form (Appendix 
3).  The patient will also be given the contact details of the Hand and Wrist Registrar/ Mr Gozzard should 
they wish to seek further information about the study. 
Recruitment will continue until 100 patients have been randomised and received the study intervention. 
 

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4.2 
PRE-REGISTRATION EVALUATIONS  
The patient participation record (Appendix 4) must be completed prior to inclusion; however there are 
no further pre-registration tests required for the patient to be included.  
 
 
 
4.3 
INCLUSION CRITERIA 
• 
Male or female ages >/= 18 years 
• 
A clinical diagnosis of trigger finger, de Quervains tenosynovitis or carpal tunnel syndrome made by 
a consultant physician.  
o Trigger finger: A diagnosis made on a history of triggering together with clinical findings of 
pain localised to the first annular pulley along with triggering of the affected digit 
o De Quervains tenosynovitis: A diagnosis made on clinical examination findings of pain over 
the first dorsal compartment, swelling localised to the first dorsal compartment and a positive 
Finklestein test. 
o Carpal tunnel syndrome: A diagnosis made on a history of intermittent paraesthesia in the 
radial 3.5 digits, with nocturnal symptoms and subjective sensory impairment and thumb 
weakness.  
• 
Treatment with corticosteroid injection is recommended by the doctor and agreed by the patient 
• 
Patient is willing and able to give informed consent for participation in the study 
 
4.4 
EXCLUSION CRITERIA 
• 
Previous surgery for the condition being treated at the desired location of injection* 
• 
Previous steroid injection for the condition being treated at the desired location of injection* 
• 
Clinical suspicion of local or systematic sepsis or infection 
• 
History of hypersensitivity to the corticosteroid or local anaesthetic  
• 
Pregnant or breast-feeding females 
• 
Unable to understand and complete self-report questionnaires written in English 
*Previous surgery or a corticosteroid injection elsewhere in the hand or wrist does not exclude the patient 
from the trial 
 
4.5 
WITHDRAWAL CRITERIA 
Patients are able to with draw from the study at any stage without prejudice.  
 
5. 
ADVERSE EVENTS 
 
5.1 
DEFINITIONS   
Term 
Definition 
Adverse Event (AE) 
Any untoward medical occurrence in a participant to whom a medicinal 
product has been administered, including occurrences which are not 
necessarily caused by or related to that product. 
Adverse Reaction 
(AR) 
 
An untoward and unintended response in a participant to an investigational 
medicinal product which is related to any dose administered to that 
participant. 
The phrase "response to an investigational medicinal product" means that a 
causal relationship between a trial medication and an AE is at least a 
reasonable possibility, i.e. the relationship cannot be ruled out. 

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All cases judged by either the reporting medically qualified professional or 
the Sponsor as having a reasonable suspected causal relationship to the trial 
medication qualify as adverse reactions. 
Serious Adverse 
Event (SAE) 
A serious adverse event is any untoward medical occurrence that: 
• results in death 
• is life-threatening 
• requires 
inpatient 
hospitalisation 
or 
prolongation 
of 
existing 
hospitalisation 
• results in persistent or significant disability/incapacity 
• consists of a congenital anomaly or birth defect 
Other ‘important medical events’ may also be considered serious if they 
jeopardise the participant or require an intervention to prevent one of the 
above consequences. 
NOTE: The term "life-threatening" in the definition of "serious" refers to an 
event in which the participant was at risk of death at the time of the event; it 
does not refer to an event which hypothetically might have caused death if it 
were more severe. 
Serious Adverse 
Reaction (SAR) 
An adverse event that is both serious and, in the opinion of the reporting 
Investigator, believed with reasonable probability to be due to one of the trial 
treatments, based on the information provided. 
Suspected 
Unexpected Serious 
Adverse Reaction 
(SUSAR) 
A serious adverse reaction, the nature and severity of which is not consistent 
with the information about the medicinal product in question set out: 
• in the case of a product with a marketing authorisation, in the summary 
of product characteristics (SmPC) for that product 
• in the case of any other investigational medicinal product, in the 
investigator’s brochure (IB) relating to the trial in question 
 
Medical judgement should be exercised in deciding whether an AE is serious in other situations.  
Important AEs that are not immediately life-threatening or do not result in death or hospitalisation but 
may jeopardise the subject or may require intervention to prevent one of the other outcomes listed in 
the definition above, should also be considered serious. 
 
5.2 
REPORTING PROCEDURES 
All adverse events should be reported.  Depending on the nature of the event the reporting procedures 
below should be followed.  Any questions concerning adverse event reporting should be directed to the 
Chief Investigator in the first instance.   
 
5.2.1 Non serious AEs 
All such events, whether expected or not, should be recorded.   
 
5.2.2 Serious AEs 
“All SAEs / SUSARs occurring from the time of written informed consent until 24 hours post cessation 
of trial treatment must be recorded on the SAE Form and e-mailed to the Sponsor within 24 hours of the 
research staff becoming aware of the event.  Once all resulting queries have been resolved, the Sponsor 
will request the original form should also be posted to the Sponsor and a copy to be retained on site. 
 
For each SAEs / SUSARs the following information will be collected: 

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• 
full details in medical terms and case description 
• 
event duration (start and end dates, if applicable) 
• 
action taken 
• 
outcome 
• 
seriousness criteria 
• 
causality (i.e. relatedness to trial drug / investigation), in the opinion of the investigator 
• 
whether the event would be considered expected or unexpected. 
Any change of condition or other follow-up information should be faxed to the Sponsor as soon as it is 
available or at least within 24 hours of the information becoming available. Events will be followed up 
until the event has resolved or a final outcome has been reached.”   
 
5.2.3 Suspected Unexpected Serious Adverse Reaction (SUSAR) 
“All SAEs assigned by the PI or delegate (or following central review by the CI and sponsor) as both 
suspected to be related to IMP-treatment and unexpected will be classified as SUSARs and will be 
subject to expedited reporting to the Medicines and Healthcare Products Regulatory Agency (MHRA). 
The Sponsor will inform the MHRA, the REC and the Sponsor of SUSARs within the required expedited 
reporting timescales.” 
 
5.2.4 Notification of deaths 
Only deaths that are assessed to be caused by the study medications (Triamcinolone and Lidocaine) 
will be reported to the sponsor.  This report will be immediate. 
 
5.2.5 Pregnancy reporting 
Pregnancy is not considered an AE unless a negative or consequential outcome is recorded for the 
mother or child/foetus. If the outcome meets the serious criteria, this would be considered an SAE. 
 
5.2.6 Overdose 
Any overdoses of the study medication will be reported to the CI immediately and will recorded as 
protocol non-compliance and as an AR/SAR if an untoward reaction is observed. 
 
5.2.7 Reporting urgent safety measures 
If any urgent safety measures are taken the CI/Sponsor shall immediately and in any event no later than 
3 days from the date the measures are taken, give written notice to the MHRA and the relevant REC of 
the measures taken and the circumstances giving rise to those measures. 
Please 
refer 
to 
the 
following 
website 
for 
details 
on 
clinical 
trials 
safety 
reporting: 
http://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Clinicaltrials/Safetyreporting-
SUSARSandASRs/index.htm  
 
5.3 
RESPONSIBILITIES 
5.3.1 Principal Investigator (PI):  
Checking for AEs and ARs when participants attend for treatment / follow-up. 
1. 
Using medical judgement in assigning seriousness, causality and expectedness using the 
Reference Safety Information approved for the trial. 
2. 
Using medical judgement in assigning seriousness and causality and providing an opinion on 
expectedness using the Reference Safety Information approved for the trial.  
3. 
Ensuring that all SAEs and SARs (including SUSARs) are recorded and reported to the Sponsor 
within 24 hours of becoming aware of the event and provide further follow-up information as soon 

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as available. Ensuring that SAEs and SARs (including SUSARs) are chased with Sponsor if a 
record of receipt is not received within 2 working days of initial reporting.  
4. 
Ensuring that AEs and ARs are recorded and reported to the Sponsor in line with the 
requirements of the protocol.  
 
 
 
5.3.2  Chief Investigator (CI) or delegate: 
1. 
Clinical oversight of the safety of patients participating in the trial, including an ongoing review of 
the risk / benefit. 
2. 
Using medical judgement in assigning seriousness, causality and expectedness of SAEs where 
it has not been possible to obtain local medical assessment. 
3. 
Using medical judgement in assigning expectedness. 
4. 
Immediate review of all SUSARs.  
5. 
Review of specific SAEs and SARs in accordance with the trial risk assessment and protocol as 
detailed in the Trial Monitoring Plan. 
 
5.3.3  Sponsor: 
1. 
Acknowledgement of reported SAEs, SARs and SUSARs according to the trial protocol.  
2. 
Expedited reporting of SUSARs and Urgent Safety Measures to the Competent Authority (MHRA 
in UK) and REC within required timelines. 
3. 
The unblinding of a participant for the purpose of expedited SUSAR reporting. 
4. 
Checking for (annually) and notifying PIs of updates to the Reference Safety Information for the 
trial. 
5. 
Preparing standard tables and other relevant information for annual reports in collaboration with 
the CI and ensuring timely submission to the MHRA and REC. 
 
 
6. 
ASSESSMENT AND FOLLOW-UP  
The end of the trial will be when the patient has completed all pain VAS scores for the documented time 
points (pre-injection, time of injection, 5-minutes after the injection, 1-hour, 2-hour, 3-hour and 24-hour 
post injection), answered the three additional questions and returned the form by post.  
 
 
7. 
STATISTICS AND DATA ANALYSIS 
 
7.1 
DESCRIPTION OF STATISTICAL METHODS 
The primary objective;  
Investigate whether there is a difference in pain VAS scores at 1-hour after a corticosteroid injection for 
trigger finger, de Quervains tenosynovitis or carpal tunnel syndrome administered with or without local 
anaesthetic.  
 
Primary outcome measure of primary objective:  
1a) A analysis of the mean change in pain VAC score between 1-hour post injection and baseline 
pre-injection will be performed. The primary intention will be the use of parametric tests 

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(Unpaired Students T-test) dependent upon the assessment of score distribution (skewness and 
kurtosis). Non-parametric testing will be employed if the mean distribution fails tests of normality.  
 
Secondary outcome measures of primary objective:  
1b) The effect size at 1-hour post injection will be calculated to measure the significance of the 
difference between the study and control group.  
 
 
 
Mean score at 1-hour  
- 
 Mean score at 1-hour 
in corticosteroid alone group                 in corticosteroid and LA group 
 
Standard deviation 
 
The objectives; 
i) Additional sensitivity analysis will be conducted to investigate whether there is a difference in pain 
VAS scores during the 24-hours after a corticosteroid injection for trigger finger, de Quervains 
tenosynovitis or carpal tunnel syndrome administered with or without local anaesthetic.  
 
Outcome measure: The cumulative pain in the 24-hour period in both groups will be calculated 
by using the area under the curve. Multilevel linear regression analysis will be conducted to 
compare 24 hour pain VAS with injection intervention nested in patient condition.   
 
ii) Additional sensitivity analysis will be conducted to investigate whether there is a difference in the pain 
VAS scores at the time of the corticosteroid injection for trigger finger, de Quervains tenosynovitis or 
carpal tunnel syndrome administered with or without local anaesthetic. 
 
 
Outcome measure: the pain VAS scores in each group at the time of the injection. Multilevel 
linear regression analysis will be conducted to compare pain VAS with injection intervention 
nested in patient condition.   
 
iii) Investigate the difference in the additional analgesia required and in the functional use of the hand 
during the first 3 hours following a corticosteroid injection for trigger finger, de Quervains tenosynovitis 
or carpal tunnel syndrome administered with or without local anaesthetic.  
 
Outcome measure: The percentage of patients requiring additional analgesia or who 
experienced worsening hand function will be determined from the three questions asked in the 
patient assessment record. The results will be presented as numbers with additional details given 
in the patients’ response, but no statistical analysis will be performed on these results.  
 
No interim or subgroup analysis will be performed.  
 
7.2 
THE NUMBER OF PARTICIPANTS 
Minimally clinical important difference of 20mm will be used as the clinically admissible margin of non-
inferiority. From previous studies, it is assumed to use a standard deviation of 25mm and with a 95% 
power calculations have determined a required sample size of 41 per study arm, when including a 20% 
fall out rate a total sample size of 100 patients will be required22.  
 
7.3 
THE LEVEL OF STATISTICAL SIGNIFICANCE 
. All statistical testing was done at the two-sided 5% significance level, and 95% CIs with Stata 14.2.  
 

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7.4 
RANDOMISATION 
Patients will be randomised using the simple randomisation service provided by Sealed Envelope Ltd 
(https://www.sealedenvelope.com).  This is an online service that provides random permuted block 
randomisation, ensuring participants are balanced between the control and treatment group. 
 
7.5 
CRITERIA FOR THE TERMINATION OF THE TRIAL. 
Once 100 patients have been recruited and randomised to the trial. 
 
7.6 
PROCEDURE FOR ACCOUNTING FOR MISSING, UNUSED, AND SPURIOUS DATA. 
A 20% fall out rate has been considered. Participants who have not returned their patient assessment 
records will not be included in the analysis. Results from partially completed forms will be included for 
analysis.   
 
7.7 
INCLUSION IN ANALYSIS 
All participants who have been randomised and have returned the patient assessment record will be 
included in an intention to treat analysis.   
 
8. 
ARCHIVING 
 
Archiving will be authorised by the Sponsor following submission of the end of study report.  All essential 
documents will be archived for a minimum of 5 years after completion of trial.  Destruction of essential 
documents will require authorisation from the study Sponsor. 
 
9. 
REGULATORY ISSUES 
 
9.1 
ETHICS APPROVAL  
The CI will obtain a positive opinion from a Health Research Authority (HRA) Research Ethics Committee 
(REC) for the study.  
The CI will also require a HRA approval letter and a Capability and Capacity e-mail statement from the 
local R&D office before accessing data for inclusion into the study. 
Any amendments to the study protocol will require review by HRA (and possibly the REC if the 
amendment is deemed to be substantial) will not be implemented until the HRA grants a favourable 
opinion for the study (note that amendments will also need to be reviewed and accepted by the NHS 
R&D department before they can be implemented in practice). 
All correspondence with the HRA will be retained in the Trial Master File/Investigator Site File. 
An annual progress report (APR) will be submitted to the HRA within 30 days of the anniversary date on 
which the favourable opinion was given, and annually until the trial is declared ended.  It is the CI’s 
responsibility to produce the annual reports as required.  The CI will also notify the HRA and sponsor of 
the end of the study.  If the study is ended prematurely, the CI will notify the REC, including the reasons 
for the premature termination. 
Within one year after the end of the study, the CI will submit a final report with the results, including any 
publications/abstracts, to the HRA.  The investigator will ensure that this study is conducted in full 
conformity with relevant national regulations and with the Department of Health Research Governance 

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Framework (2005).  The research team will also bear in mind the principles of the Declaration of Helsinki 
when conducting the study. 
 
 
 
9.1.1 Regulatory Compliance 
The trial will not commence until a Clinical Trial Authorisation (CTA) is obtained from the MHRA.  The 
protocol and trial conduct will comply with the Medicines for Human Use (Clinical Trials) Regulations 
2004 and any relevant amendments 
9.2 
CONSENT  
Consent to enter the study must be sought from each participant only after a full explanation has been 
given, an information leaflet offered and time allowed for consideration.  Signed participant consent will 
be obtained.  The right of the participant to refuse to participate without giving reasons will be respected.  
After the participant has entered the study the clinician remains free to give alternative treatment to that 
specified in the protocol at any stage if he/she feels it is in the participant’s best interest, but the reasons 
for doing so should be recorded.  In these cases the participants remain within the study for the purposes 
of follow-up and data analysis.  All participants are free to withdraw at any time from the protocol 
treatment without giving reasons and without prejudicing further treatment. 
 
9.3 
CONFIDENTIALITY 
The trial staff will ensure that the participants’ anonymity is maintained. The participants’ data will be 
pseudonymised (i.e. only initials and a study ID number on the CRF and any electronic database will 
identify participants). All documents will be stored securely and only be accessible by trial staff and 
authorised personnel. The study will comply with the Data Protection Act 2018. No participants will be 
individually identified in any subsequent publications relating to this study. 
 
9.4 
INDEMNITY 
This is an NHS-sponsored research study. If an individual suffers negligent harm as a result of 
participating in the study, NHS indemnity covers NHS staff and those people responsible for conducting 
the trial who have honorary contracts with the relevant NHS Trust.  In the case of non-negligent harm, 
the NHS is unable to agree in advance to pay compensation, but an ex-gratia payment may be 
considered in the event of a claim. 
 
9.5 
SPONSOR 
University Hospital Plymouth NHS Trust will act as the main sponsor for this study.  Delegated 
responsibilities will be assigned to other NHS trusts taking part in this study.   
 
9.6 
FUNDING 
This study will be funded by available Departmental research funds, held by the Research and 
Development department on behalf on Miss S Fullilove. Depending on the study cost analysis review 
further external funds may have to be sought.  
 
9.7 
MONITORING 
The study will be subject to monitoring by University Hospitals Plymouth NHS Trust under their remit as 
sponsor to ensure adherence to the UK Policy Framework for Health and Social Care Research (2017).  
All UHP studies will be initially monitored at 25 days (+/- 7 days) after R&D capability and capacity has 
been given.  The subsequent level of monitoring will be determined by a risk assessment, or on a for 
cause basis.  The study may also be audited / inspected by regulatory bodies to ensure compliance with 
national regulations. 

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10. 
STUDY MANAGEMENT 
The study management group will meet monthly to monitor study process, patient recruitment and 
potential issues, which may arise. These meetings will include the study management group, consultant 
sectaries and a member of the R&D team. Minutes will be taken and distributed and any members not 
on site will have to option to teleconference in.    
 
11. 
PUBLICATION POLICY 
It is proposed that the study team will prepare a plain English summary of the study results, which will 
be sent to the study participants as soon as possible after the end of the study.  The final results of the 
study will be disseminated via presentations at appropriate scientific meetings and conferences and 
publication in appropriate peer-reviewed journals. Mr Matt Jones will be named as first author in any 
presentation or publications.  
 
12. 
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