BIMAtoprost eye drops in thyroid eye disease
| ISRCTN | ISRCTN46696624 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN46696624 |
| EudraCT/CTIS number | 2014-000540-15 |
| ClinicalTrials.gov number | NCT02059655 |
| Secondary identifying numbers | SPON1266-14 |
- Submission date
- 07/02/2014
- Registration date
- 14/03/2014
- Last edited
- 09/08/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English summary of protocol
Background and study aims
Thyroid eye disease (TED) is a chronic disfiguring and debilitating disease of the eyes which can lead to sight loss in severe cases. Patients with TED often have characteristic eyeball protrusion (proptosis) due to increased fat accumulation behind the eye. The discomfort and changes in appearance of the eyes is a source of severe psychological distress and reduced quality of life in many patients. Current treatments for TED are unsatisfactory and established nonsurgical therapies which specifically reduce proptosis are lacking. Reduced eyelid protrusion has recently been reported as a side effect of the use of prostaglandin analogue eye drops such as Bimatoprost (PGF2alpha) in the routine treatment of glaucoma and we have data showing inhibition of fat cells by Bimatoprost. Hence PGF2alpha eye drops potentially represent a simple, non-invasive low-toxicity alternative to surgery in TED. However, no clinical trials of Bimatoprost have been conducted in TED to date. The aim of this study is to determine whether Bimatoprost eye drops are effective in reducing proptosis and thus improving quality of life in patients with TED.
Who can participate?
Men and women aged 18 years and older from the TED clinic at the University Hospital Wales (Cardiff & Vale University Health Board). Only participants with stable, late, inactive thyroid eye disease will be enrolled. The clinic is a regional referral centre for the treatment and study of TED and is run by a multidisciplinary team of ophthalmologists, endocrinologists, and orthoptists with expertise in TED.
What does the study involve?
Following informed consent, you will be randomly allocated to use Bimatoprost or placebo (dummy) eye drops daily for three months, after which you will not use eye drops for two months, before switching to the opposite treatment in the final three months of the study. Patients will be followed up at one further visit 2 months later. You will be enrolled in the study for 10 months in total. There are six visits: before the start of the study, random allocation and four follow-up visits. You will be asked to complete quality of life questionnaires and a health economic questionnaire at each of the follow-up visits. Eye tests will be carried out before the start of the study and at follow-up visits.
What are the possible benefits and risks of participating?
If the treatment you are receiving is found to be better than the current standard treatment then you will benefit from participating in this study. Otherwise, taking part may not be of direct benefit to you. It should, however, help us to provide better care for patients with Thyroid Eye Disease in the future. Note that all participants will receive the active treatment at one stage of the study. The most common side effects after using Bimatoprost eye drops are an itching sensation in the eyes and/or eye redness. This was reported in about 4% of patients. Bimatoprost may cause other less common side effects which typically occur on the skin close to where it is applied, or in the eyes. These include skin darkening, longer or thicker eyelashes, dryness of the eyes and redness of the eyelids. Any eyelid skin darkening or eye lash thickening/elongation are expected to reverse after several weeks to months after stopping the eye drops. Bimatoprost use may also cause increased brown pigmentation (reported in about 1% of patients) of the coloured part of the eye known as iris which may be permanent. Bimatoprost eye drops have been in routine long-term clinical use in glaucoma for 12 years, and will be used in this study at the same dose as in glaucoma therapy. Drug formulations containing Bimatoprost have been in regular use for glaucoma for some time, and Bimatoprost preparations are available over the counter for cosmetic application, thus their safety is well established.
Where is the study run from?
University Hospital of Wales, Cardiff & Vale University Health Board, UK.
When is the study starting and how long is it expected to run for?
It is expected that recruitment will start in May 2014. You will be enrolled on the study for 10 months; however, it is expected that the study will run until February 2016 to complete data analysis.
Who is funding the study?
Research for Patient and Public Benefit Wales, part of National Institute for Social Care & Health Research (NISCHR), UK.
Who is the main contact?
Professor Colin Dayan
DayanCM@cardiff.ac.uk
Contact information
Scientific
Institute of Molecular & Experimental Medicine
Cardiff University School of Medicine
University Hospital of Wales
C2 Link Corridor
Heath Park
Cardiff
CF14 4XW
United Kingdom
 ORCID ID |
0000-0002-6557-3462 |
|---|---|
| Phone | +44 (0)29 20 742182 |
| DayanCM@cardiff.ac.uk |
Study information
| Study design | Randomised placebo-controlled double-blind crossover design |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Prostaglandin F2-alpha eye drops (BIMAtoprost) in thyroid eye disease: a randomised controlled double blind crossover trial |
| Study acronym | BIMA |
| Study objectives | We hypothesise that topical treatment with Bimatoprost may reduce orbital tissue volume in noninflamed orbits and thereby improve quality of life in patients with thyroid eye disease (TED). |
| Ethics approval(s) | Wales REC 3, initial approval obtained on 21/03/2014, REC reference: 14/WA/0081, substantial amendment 1 on 17/06/2014 |
| Health condition(s) or problem(s) studied | Graves' eye disease |
| Intervention | Bimatoprost or placebo eye drops (daily application) for three months followed by a two-month drug washout period before switching to the opposite treatment in the final three months of study. 1 drop daily for 3 months (placebo or Bimatoprost) Stop treatment for following 2 months 1 drop daily for following 3 months (cross over to either placebo or Bimatoprost) Patients will be followed up at one further visit 2 months later |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Bimatoprost |
| Primary outcome measure | Change in proptosis measurement; reduction of 2 mm or more would be regarded as clinically relevant. Measured at all visits (baseline, 2, 3, 4, 5). Measured by exophthalmometry readings by Hertel exophthalmometer. |
| Secondary outcome measures | 1. Change in quality of life scores: measured at visits 1, 2, 3, 4, 5. Measured by EUGOGO GO-Quality of Life and EQ-5D-5L Health Questionnaire 2. Side effects: measured at visits 2, 3, 4, 5. Standardised questionnaire in the form of a patient diary log. Patients will be requested to record any side effects in their diary 3. Change in intraocular pressure: measured at visits baseline, 2, 3, 4, 5. Measured by Goldmann Applanation Tonometer 4. Health economic cost: measured at visits 1, 2, 3, 4, 5. Measured by Client Service Receipt Inventory (CSRI) |
| Overall study start date | 05/12/2012 |
| Completion date | 15/04/2016 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 31 |
| Total final enrolment | 31 |
| Key inclusion criteria | 1. Stable TED with no reported change in proptosis for at least 6 months 2. Clinical activity score <3 3. Proptosis (subjective unilateral proptosis confirmed by asymmetry in exophthalmometry of >2 mm OR greater than 20 mm on exophthalmometry measurement in one eye) 4. Euthyroid (FT3 and FT4 in the reference range) 5. If female, must be using a reliable form of contraception during the trial, e.g. oral contraceptive and condom, intrauterine device (IUD) and condom, diaphragm with spermicide and condom |
| Key exclusion criteria | 1. Age <18 years 2. Dysthyroid optic neuropathy unless previously treated 3. Pregnancy or lactation 4. Previous corneal herpes simplex infection 5. On therapy for glaucoma or intraocular hypertension 6. Less than 6 months from prior steroid use 7. Aphakia, pseudophakia with torn posterior lens capsule or anterior chamber lenses 8. Patient with risk factors for cystoid macular oedema, iritis or uveitis 9. Severe asthma (risk of severe allergic reaction to medication). 10. Previous allergy to Bimatoprost or preservative |
| Date of first enrolment | 20/11/2014 |
| Date of final enrolment | 12/02/2015 |
Locations
Countries of recruitment
- United Kingdom
- Wales
Study participating centre
CF14 4XW
United Kingdom
Sponsor information
University/education
Research, Innovation & Enterprise Services (RIES)
MacKenzie House
30-36 Newport Road
Cardiff
CF24 0DE
Wales
United Kingdom
| Website | http://www.cf.ac.uk/racdv/resgov/index.html |
|---|---|
"ROR" |
https://ror.org/03kk7td41 |
Funders
Funder type
Government
No information available
Results and Publications
| Intention to publish date | 31/12/2018 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | It is intended that the results of the study will be reported and disseminated at local and international conferences and in peer-reviewed scientific journals. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/04/2019 | 13/06/2019 | Yes | No |
| Basic results | 09/08/2019 | No | No | ||
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
09/08/2019: The following changes were made to the trial record:
1. ClinicalTrials.gov number added.
2. Proactive update review. Added clinicaltrialsregister.eu link to basic results (scientific).
13/06/2019: Publication reference and total final enrolment added.
02/05/2018: The following changes were made:
1. Overall trial start date was changed from 01/05/2014 to 05/12/2012
2. Recruitment start date was changed from 01/05/2014 to 20/11/2014
3. Recruitment end date was changed from to 29/02/2016 12/02/2015
4. Overall trial end date was changed from 29/02/2016 to 15/04/2016
5. ORCID, publication and dissemination plan and participant level data were added.
27/03/2018: No publications found, verifying study status with principal investigator.
