Plain English Summary
Background and study aims
Shingles is a viral infection that causes a painful rash. This study aims to find out whether taking a low dose of amitriptyline soon after getting shingles can prevent the long-term pain associated with shingles
Who can participate?
Patients aged over 50 years who have been diagnosed by their GP with shingles.
What does the study involve?
Participants take tablets nightly for 10 weeks: half will be given low dose amitriptyline and the other half will get placebo (dummy) tablets. Pain is assessed at 90 days after rash onset.
What are the possible benefits and risks of participating?
If starting amitriptyline early on does help, it is a cheap medicine that would prevent prolonged, difficult-to-treat pain for thousands of people. However, amitriptyline commonly causes side effects such as dizziness, dry mouth and constipation. It can also cause problems when used together with some other tablets. This study is needed so doctors can be sure that any benefits outweigh any harms.
Where is the study run from?
1. University of Bristol (UK)
2. Southampton University (UK)
3. Oxford University (UK)
When is the study starting and how long is it expected to run for?
July 2021 to June 2024
Who is funding the study?
National Institute for Health Research (NIHR) (UK)
Who is the main contact?
athena-study@bristol.ac.uk
Study website
Contact information
Type
Scientific
Contact name
Dr Sian Wells
ORCID ID
Contact details
Centre for Academic Primary Care
Bristol Medical School
University of Bristol
Canynge Hall
39 Whatley Rd
Bristol
BS8 2PS
United Kingdom
+44 (0)117 9287308
athena-study@bristol.ac.uk
Type
Scientific
Contact name
Prof Matthew Ridd
ORCID ID
Contact details
Centre for Academic Primary Care
Bristol Medical School
University of Bristol
Canynge Hall
39 Whatley Rd
Bristol
BS8 2PS
United Kingdom
+44 (0)117 33 14557
m.ridd@bristol.ac.uk
Additional identifiers
EudraCT/CTIS number
2021-001101-78
IRAS number
1003967
ClinicalTrials.gov number
Nil known
Protocol/serial number
CPMS 50893, IRAS 1003967
Study information
Scientific title
Amitriptyline for the prevention of post-herpetic neuralgia
Acronym
ATHENA
Study hypothesis
Prophylactic low-dose amitriptyline will reduce post-herpetic neuralgia in patients diagnosed with herpes zoster (shingles).
Ethics approval(s)
Approved 18/10/2021, South West- Central Bristol Research Ethics Committee (Ground Floor, Temple Quay House, 2 The Square, Bristol, BS1 6PN, UK; +44 (0)207 104 8029, +44 (0)207 104 8068, +44 (0)207 104 8375; centralbristol.rec@hra.nhs.uk), REC ref: 21/SW/0130
Study design
Randomized; Interventional; Design type: Treatment, Drug
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Study setting(s)
GP practice
Study type
Treatment
Patient information sheet
https://athena-study.blogs.bristol.ac.uk/files/2022/01/ATHENA-PIL.pdf
Condition
Shingles
Intervention
Amitriptyline 10 mg tablets (or matched placebo tablet), increasing in 10 mg steps over 2 weeks as tolerated, to 30 mg maximum per day, for 70 days.
Total follow-up is 12 months, with participant surveys at baseline and 30, 60, 90, 120, 180 and 360 days after rash onset.
Randomisation:
Trial participants will be allocated in a 1:1 ratio to receive amitriptyline or placebo. Randomisation will be stratified by centre and minimised on age deciles, gender at birth, pain in the last 24 hours and shingles vaccination history. The randomisation sequence will be generated by the company Sealed Envelope™ using their online randomisation system, which will allocate the participant to a treatment arm. The person undertaking the randomisation and the participant will remain masked as to which treatment group this code refers.
Intervention type
Drug
Pharmaceutical study type(s)
Phase
Not Applicable
Drug/device/biological/vaccine name(s)
Amitriptyline
Primary outcome measure
Presence/absence of postherpetic neuralgia measured using a cut-off of ≥3/10 on numerical rating scale average pain in last 24 hours; Timepoint(s): 90 days after rash onset
Secondary outcome measures
1. The safety, tolerability and acceptability of amitriptyline assessed using patient-completed medication use, problems and hospitalisation sections of questionnaire at 30, 60 and 90 days, and by direct report by participant or clinician
2. Masking of participants assessed using the bang binding index in patient questionnaires at 30, 60 and 90 days post rash onset
3. Shorter and longer-term outcomes of pain, quality of life, mental well-being and frailty, assessed using the Zoster Brief Pain Inventory (ZBPI), 9-item patient health questionnaire (PHQ-9), 7-item general anxiety disorder questionnaire (GAD-7) and Tilburg Frailty Indicator, at 0, 90, 180 and 360 days post rash onset
4. The cost-effectiveness of low dose amitriptyline to placebo for the prevention of PHN using EQ-5D-5L and patient-completed healthcare resource use questions at 0, 90, 180 and 360 days post rash onset, and GP electronic medical records for the 12-month study period
5. Use of healthcare resources and analgesics assessed using patient-completed medication and healthcare resource use questions at 90, 180 and 360 days post rash onset, and GP electronic medical records for the 12-month study period
Overall study start date
01/07/2021
Overall study end date
30/06/2024
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Adults aged ≥50 years
2. Clinical diagnosis of herpes zoster (HZ)
3. Rash onset <144 hours
Participant type(s)
Patient
Age group
Adult
Lower age limit
50 Years
Sex
Both
Target number of participants
Planned Sample Size: 846; UK Sample Size: 846
Participant exclusion criteria
1. Inability to give informed consent
2. Third or more episode of herpes zoster
3. Known adverse reaction to amitriptyline or contraindications (monoamine oxidase inhibitors)
4. Current/recent (within previous two weeks) use of a tricyclic antidepressant
5. Prolonged QT interval or concomitant drugs that prolong the QT interval
6. Suicidal ideation
7. Heart block
8. Recent myocardial infarction (<4 weeks)
9. Immunosuppression
10. Significant bradycardia
11. Uncompensated heart failure
12. Hyperthyroidism
13. Severe liver disease
14. Phaeochromocytoma
15. Urinary retention
16. If female; current or planned (in next 3 months) pregnancy or breastfeeding
17. Currently (or recently, within the previous 4 months) enrolled in another CTIMP
Recruitment start date
30/03/2022
Recruitment end date
30/11/2023
Locations
Countries of recruitment
England, United Kingdom
Study participating centre
University of Bristol
Senate House
Tyndall Avenue
Bristol
BS8 1TH
United Kingdom
Study participating centre
University of Oxford
University Offices
Oxford
OX1 2JD
United Kingdom
Study participating centre
University of Southampton
University Road
Southampton
SO17 1BJ
United Kingdom
Sponsor information
Organisation
University of Bristol
Sponsor details
1 Cathedral Square
Trinity Street
College Green
Bristol
BS1 5DD
England
United Kingdom
+44 (0)117 394 0177
research-governance@bristol.ac.uk
Sponsor type
University/education
Website
ROR
Funders
Funder type
Government
Funder name
NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: NIHR129720
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer-reviewed journal in approximately 2025. The researchers will publish a protocol in due course.
Intention to publish date
30/06/2025
Individual participant data (IPD) sharing plan
The final anonymised trial data set will be stored as restricted data on the data.bris research data repository for at least 5 years after the end of the study. Data will be made available after the end of the study to approved bona fide researchers only after their host institution has signed a data access agreement. Details of how to request access are available at the University of Bristol’s data repository website.
IPD sharing plan summary
Stored in non-publicly available repository
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |