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

Primary Purpose

Graves' Ophthalmopathy

Status
Completed
Phase
Phase 4
Locations
United Kingdom
Study Type
Interventional
Intervention
Bimatoprost
Eye drop solution
Sponsored by
Cardiff University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Graves' Ophthalmopathy focused on measuring Graves' disease

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University Hospital of Wales

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Eye drop solution

Bimatoprost

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
Intraocular pressures
Whether there has been a change in intraocular pressures
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
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

Full Information

First Posted
February 7, 2014
Last Updated
May 5, 2016
Sponsor
Cardiff University
Collaborators
National Institute for Social Care and Health Research
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1. Study Identification

Unique Protocol Identification Number
NCT02059655
Brief Title
Prostaglandin F2-alpha Eye Drops in Thyroid Eye Disease (Bima Study)
Acronym
BIMA
Official Title
Prostaglandin F2-alpha Eye Drops (Bimatoprost) in Thyroid Eye Disease: a Randomised Controlled Double Blind Crossover Trial
Study Type
Interventional

2. Study Status

Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
November 2014 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
March 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Cardiff University
Collaborators
National Institute for Social Care and Health Research

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graves' Ophthalmopathy
Keywords
Graves' disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Eye drop solution
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Bimatoprost
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bimatoprost
Other Intervention Name(s)
Trade Name Lumigan. MA number: EU/1/02/205/001-002. ATC Code: S01EE03
Intervention Type
Drug
Intervention Name(s)
Eye drop solution
Other Intervention Name(s)
1 drop daily, Hypromellose Ph Eur 0.3g in 100ml, Sodium chloride, Potassium chloride, Borax, Boric acid, Benzalkonium chloride solution, Purified water, Sodium hydroxide solution (to adjust pH), Hydrochloric acid
Intervention Description
Artificial tear drops
Primary Outcome Measure Information:
Title
The primary endpoint of this study will be comparison of the change in ophthalmometry readings over the two 3 month treatment periods.
Description
Reduction of 2 mm or more is regarded as clinically relevant
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Change in quality of life scores on the TED quality of life questionnaire (GO-QOL)
Description
Whether there has been an improvement in patients' quality of life
Time Frame
1 year
Title
Intraocular pressures
Description
Whether there has been a change in intraocular pressures
Time Frame
1 year
Title
Side effects
Description
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
Time Frame
1 year
Title
Health economic outcomes
Description
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
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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; 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Colin M Dayan, MA FRCP PhD
Organizational Affiliation
Cardiff University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital of Wales
City
Cardiff
ZIP/Postal Code
CF14 4XW
Country
United Kingdom

12. IPD Sharing Statement

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

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