Graves' OphthalmopathyPhase 4BIMANCT02059655
Prostaglandin F2-alpha Eye Drops in Thyroid Eye Disease (Bima Study)
A Phase 4 study testing Bimatoprost and Eye drop solution in people with Graves' Ophthalmopathy, run by Cardiff University at 1 site in United Kingdom.
Trial summary
The purpose of the study is to establish whether Bimatoprost eye drops are effective in reducing proptosis in inactive thyroid eye disease (TED) patients and improving quality of life in patients with TED. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Graves' Ophthalmopathy
- What is being tested?
- Bimatoprost and Eye drop solution
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Nov 2014to Mar 2016
- Phase
- Phase 4
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Stable TED with no reported change in proptosis for at least 6 months. See section 4.1.1 for TED definition;
- Clinical activity score <3 (Appendix 1);
- Proptosis (subjective unilateral proptosis confirmed by asymmetry in exophthalmometry of >2mm OR greater than 20 mm on exophthalmometry measurement in one eye);
- Euthyroid (thyroid function tests in the reference range);
- If female, must be using a reliable form of contraception during the trial, e.g. oral contraceptive and condom, intra-uterine device (IUD) and condom, diaphragm with spermicide and condom.
Who cannot join
- Age <18 yrs;
- Dysthyroid optic neuropathy unless previously treated;
- Pregnancy or lactation;
- Previous Corneal Herpes Simplex infection;
- On therapy for glaucoma or intraocular hypertension;
- Less than 6 months from prior systemic steroid use;
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- Aphakia, pseudophakia with torn posterior lens capsule or anterior chamber lenses;
- Patient with risk factors for cystoid macular oedema, iritis or uveitis;
- Severe Asthma (risk of severe allergic reaction to medication);
- Previous allergy to Bimatoprost or preservative.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University Hospital of Wales
Cardiff, Cardiff, CF14 4XW
About this study
Official title: Prostaglandin F2-alpha Eye Drops (Bimatoprost) in Thyroid Eye Disease: a Randomised Controlled Double Blind Crossover Trial
The purpose of the study is to establish whether Bimatoprost eye drops are effective in reducing proptosis in inactive thyroid eye disease (TED) patients and improving quality of life in patients with TED. Current standard NHS treatment/care for inactive TED is artificial tears (used as the placebo in this study) or surgery if appropriate.
The IMP is Bimatoprost eye drops PGF2α (0.03%). This is already licensed eye drops usually used for glaucoma. Therefore the current trial's indication is outside its licenced indication. The Investigational Medicinal Product (IMP) will be used according to its licenced dosage and form. This is the first time that Bimatoprost will be used in the treatment of TED
Read the detailed description
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 frequently 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 impaired quality of life in many patients. Current treatments for TED are unsatisfactory and established non-surgical 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 (e.g. Bimatoprost (PGF2-alpha)) in the routine treatment of glaucoma and we have laboratory data showing inhibition of fat cells by Bimatoprost. Hence PGF2-alpha eye drops potentially represent a simple, non-invasive low toxicity topical alternative to surgery in TED. However no clinical trials of Bimatoprost have been conducted in TED to date. The objective 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. Trial participants will be recruited from the TED clinic at the University Hospital Wales. 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. Following informed consent, participants will be randomised to receive Bimatoprost or placebo eye drops for three months after which they will undergo a two month drug washout period before switching to the opposite treatment in the final three months of study. The primary endpoint is a change in standardised measurements of proptosis while secondary endpoints will include changes in quality of life scores. This study will provide evidence for a novel application of bimatoprost in patients with TED.
- Conditions
- Graves' Ophthalmopathy
- Being tested
- Bimatoprost, Eye drop solution
- Keywords
- Graves' disease
- Medical subject headings
- Graves Ophthalmopathy, Graves Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BimatoprostDrug
Also called Trade Name Lumigan. MA number: EU/1/02/205/001-002. ATC Code: S01EE03
Eye drop solutionDrug
Also called 1 drop daily, Hypromellose Ph Eur 0.3g in 100ml, Sodium chloride, Potassium chloride
Artificial tear drops
| Study group | Role | What they receive |
|---|---|---|
| Eye drop solution | Placebo comparator | Patients will receive 1 dose daily over 3 month period followed by 2 months washout period. Subsequently patient will cross over to the opposite treatment and continue further treatment for 3 month period. Receives: Drug: Eye drop solution |
| Bimatoprost | Active comparator | 1 drop daily of Bimatoprost 0.03%. Patients will receive 1 dose daily over 3 month period followed by 2 months washout period. Subsequently patient will cross over to the opposite treatment and continue further treatment for 3 month period. Receives: Drug: Bimatoprost |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint of this study will be comparison of the change in ophthalmometry readings over the two 3 month treatment periods.
Reduction of 2 mm or more is regarded as clinically relevant
Measured: 1 year
Secondary outcomes (4)
Change in quality of life scores on the TED quality of life questionnaire (GO-QOL)
Whether there has been an improvement in patients' quality of life
Measured: 1 year
Intraocular pressures
Whether there has been a change in intraocular pressures
Measured: 1 year
Side effects
To consider the side effect profiles of Bimatoprost in TED patients during the study.
Expected Adverse Reactions to the trial treatment(s) are detailed below:
- Commonly occurring cosmetic effects (approximate incidence)
- Conjunctival redness (0.5%);
- Lengthening of eyelashes - (average elongation 0.7mm);
- Darkening of eye lashes (45-57%);
- Peri-ocular skin pigmentation (3%);
- Darkening of the iris (10.1%).
- Rare but potentially serious side effects (limited information available)
- Iris cysts;
- Cystoid macular oedema;
- Anterior uveitis;
- Reactivation of herpes simplex virus infection
Measured: 1 year
Health economic outcomes
The primary intention of the economic evaluation is to explore the cost associated with TED treatment. In theory, Bimatoprost intervention would lead to the net cost savings to NHS in comparison to surgical rehabilitation that the patient otherwise will go through. We are aware of limitation in the trial design as this trial primary intention is to evaluate efficacy of Bimatoprost in TED, not to follow up patients until they might need surgery. However it would be useful to collect the resource use and quality of life data during this trial period on a pilot basis which may lead to a larger health economic focus study in the future. It is not envisaged that the crossover design will yield data that could allow a meaningful incremental cost-effectiveness ratio (ICER) to be calculated for Bimatoprost against placebo, as the duration of effects on perceived quality of life cannot be predicted in advance
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2014 (estimated)
- Study startNov 2014
- Primary completionMar 2016
- Study completionMar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graves' OphthalmopathyStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cardiff University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Social Care and Health Research
- Responsible party
- Principal investigator, Professor Colin Dayan, Cardiff University
- Investigators
- Colin M Dayan, MA FRCP PhD, Principal investigator, Cardiff University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02059655
- Sponsor's protocol ID
- SPON 1266-14
- Acronym
- BIMA
- Status last verified
- May 2016
- First submitted
- 7 Feb 2014
- Last updated
- 6 May 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prostaglandin F2-alpha Eye Drops (Bimatoprost) in Thyroid Eye Disease: a Randomised Controlled Double Blind Crossover Trial
- ClinicalTrials.gov ID
- NCT02059655
- Acronym / sponsor ID
- BIMA / SPON 1266-14
- Conditions
- Graves' Ophthalmopathy
- Keywords
- Graves' disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Cardiff UniversityUniversity, hospital or other
- Collaborators
- National Institute for Social Care and Health Research
- Study start
- Nov 2014
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 11 Feb 2014 (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 purpose of the study is to establish whether Bimatoprost eye drops are effective in reducing proptosis in inactive thyroid eye disease (TED) patients and improving quality of life in patients with TED. Current standard NHS treatment/care for inactive TED is artificial tears (used as the placebo in this study) or surgery if appropriate.
The IMP is Bimatoprost eye drops PGF2α (0.03%). This is already licensed eye drops usually used for glaucoma. Therefore the current trial's indication is outside its licenced indication. The Investigational Medicinal Product (IMP) will be used according to its licenced dosage and form. This is the first time that Bimatoprost will be used in the treatment of TED
Detailed description
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 frequently 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 impaired quality of life in many patients. Current treatments for TED are unsatisfactory and established non-surgical 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 (e.g. Bimatoprost (PGF2-alpha)) in the routine treatment of glaucoma and we have laboratory data showing inhibition of fat cells by Bimatoprost. Hence PGF2-alpha eye drops potentially represent a simple, non-invasive low toxicity topical alternative to surgery in TED. However no clinical trials of Bimatoprost have been conducted in TED to date. The objective 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. Trial participants will be recruited from the TED clinic at the University Hospital Wales. 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. Following informed consent, participants will be randomised to receive Bimatoprost or placebo eye drops for three months after which they will undergo a two month drug washout period before switching to the opposite treatment in the final three months of study. The primary endpoint is a change in standardised measurements of proptosis while secondary endpoints will include changes in quality of life scores. This study will provide evidence for a novel application of bimatoprost in patients with TED.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Eye drop solution | Placebo comparator | Drug: Eye drop solutionPatients will receive 1 dose daily over 3 month period followed by 2 months washout period. Subsequently patient will cross over to the opposite treatment and continue further treatment for 3 month period. |
| Bimatoprost | Active comparator | Drug: Bimatoprost1 drop daily of Bimatoprost 0.03%. Patients will receive 1 dose daily over 3 month period followed by 2 months washout period. Subsequently patient will cross over to the opposite treatment and continue further treatment for 3 month period. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Stable TED with no reported change in proptosis for at least 6 months. See section 4.1.1 for TED definition;
- Clinical activity score <3 (Appendix 1);
- Proptosis (subjective unilateral proptosis confirmed by asymmetry in exophthalmometry of >2mm OR greater than 20 mm on exophthalmometry measurement in one eye);
- Euthyroid (thyroid function tests in the reference range);
- If female, must be using a reliable form of contraception during the trial, e.g. oral contraceptive and condom, intra-uterine device (IUD) and condom, diaphragm with spermicide and condom.
Key exclusion criteria (10 listed)
- Age <18 yrs;
- Dysthyroid optic neuropathy unless previously treated;
- Pregnancy or lactation;
- Previous Corneal Herpes Simplex infection;
- On therapy for glaucoma or intraocular hypertension;
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 |
|---|---|---|
| BimatoprostAlso: Trade Name Lumigan. MA number: EU/1/02/205/001-002. ATC Code: S01EE03 | Drug | Bimatoprost |
| Eye drop solutionAlso: 1 drop daily, Hypromellose Ph Eur 0.3g in 100ml, Sodium chloride, Potassium chlorideArtificial tear drops | Drug | Eye drop solution |
Primary outcome
The primary endpoint of this study will be comparison of the change in ophthalmometry readings over the two 3 month treatment periods.
Time frame: 1 year
Reduction of 2 mm or more is regarded as clinically relevant
4 secondary outcomes
Change in quality of life scores on the TED quality of life questionnaire (GO-QOL)
Time frame: 1 year
Intraocular pressures
Time frame: 1 year
Side effects
Time frame: 1 year
Health economic outcomes
Time frame: 1 year
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 May 2016.
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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.
Colin M Dayan, MA FRCP PhD principal investigator
Cardiff University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bimatoprost and Eye drop solution in people with Graves' Ophthalmopathy, run by Cardiff University at 1 site in United Kingdom.
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 5 inclusion and 10 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 May 2016. 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 United Kingdom. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
The primary endpoint of this study will be comparison of the change in ophthalmometry readings over the two 3 month treatment periods. (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 May 2016.