Prostaglandin F2-alpha Eye Drops in Thyroid Eye Disease (Bima Study)

Graves' Ophthalmopathy Clinical Trial

— BIMA  

Official title:

Prostaglandin F2-alpha Eye Drops (Bimatoprost) in Thyroid Eye Disease: a Randomised Controlled Double Blind Crossover Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02059655
• Other study ID #: SPON 1266-14
• Status: Completed
• Phase: Phase 4
• First received: February 7, 2014
• Last updated: May 5, 2016
• Start date: November 2014
• Est. completion date: March 2016

Study information

• Verified date: May 2016
• Source: Cardiff University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical 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. 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Stable TED with no reported change in proptosis for at least 6 months. See section 4.1.1 for TED definition;

2. Clinical activity score <3 (Appendix 1);

3. Proptosis (subjective unilateral proptosis confirmed by asymmetry in exophthalmometry of >2mm OR greater than 20 mm on exophthalmometry measurement in one eye);

4. Euthyroid (thyroid function tests in the reference range);

5. 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.

Exclusion Criteria:

1. Age <18 yrs;

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 systemic 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Eye Diseases
• Graves Ophthalmopathy
• Graves' Ophthalmopathy

Intervention

Drug:
• Bimatoprost

• Eye drop solution
Artificial tear drops

Locations

Country	Name	City	State
United Kingdom	University Hospital of Wales	Cardiff

Sponsors (2)

Lead Sponsor	Collaborator
Cardiff University	National Institute for Social Care and Health Research

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	1 year	Yes
Secondary	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	1 year	No
Secondary	Intraocular pressures	Whether there has been a change in intraocular pressures	1 year	No
Secondary	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	1 year	Yes
Secondary	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	1 year	No

External Links

•   Cardiff University, School of Medicine, Diabetes & Endocrinology Clinical Trials