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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2014 by Cardiff University
Sponsor:
Collaborator:
National Institute for Social Care and Health Research
Information provided by (Responsible Party):
Professor Colin Dayan, Cardiff University
ClinicalTrials.gov Identifier:
NCT02059655
First received: February 7, 2014
Last updated: February 11, 2014
Last verified: February 2014
  Purpose

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


Condition Intervention Phase
Graves' Ophthalmopathy
Drug: Bimatoprost
Drug: Eye drop solution
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Prostaglandin F2-alpha Eye Drops (Bimatoprost) in Thyroid Eye Disease: a Randomised Controlled Double Blind Crossover Trial

Resource links provided by NLM:


Further study details as provided by Cardiff University:

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. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Whether there has been an improvement in patients' quality of life

  • Intraocular pressures [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Whether there has been a change in intraocular pressures

  • Side effects [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

    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:

    1. 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%).
    2. 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 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 31
Study Start Date: May 2014
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Eye drop solution
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.
Drug: Eye drop solution
Artificial tear drops
Other Names:
  • 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
Active Comparator: Bimatoprost
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.
Drug: Bimatoprost
Other Name: Trade Name Lumigan. MA number: EU/1/02/205/001-002. ATC Code: S01EE03

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02059655

Contacts
Contact: Shazli Draman, MRCPI 02920748481 DramanYusofMS@cardiff.ac.uk
Contact: Julie C Pell, PgC 029744370 pelljc@cardiff.ac.uk

Locations
United Kingdom
University Hospital of Wales Not yet recruiting
Cardiff, United Kingdom, CF14 4XW
Contact: Colin M Dayan, MA FRCP PhD    029 20 742182    DayanCM@cardiff.ac.uk   
Contact: Shazli Draman, MRCPI    02920748481    DramanYusofMS@cardiff.ac.uk   
Principal Investigator: Colin M Dayan, MA FRCP PhD         
Sponsors and Collaborators
Cardiff University
National Institute for Social Care and Health Research
Investigators
Principal Investigator: Colin M Dayan, MA FRCP PhD Cardiff University
  More Information

Additional Information:
No publications provided

Responsible Party: Professor Colin Dayan, Professor, Cardiff University
ClinicalTrials.gov Identifier: NCT02059655     History of Changes
Other Study ID Numbers: SPON 1266-14
Study First Received: February 7, 2014
Last Updated: February 11, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Cardiff University:
Graves' disease

Additional relevant MeSH terms:
Graves Disease
Eye Diseases
Graves Ophthalmopathy
Eye Diseases, Hereditary
Exophthalmos
Orbital Diseases
Goiter
Thyroid Diseases
Endocrine System Diseases
Hyperthyroidism
Autoimmune Diseases
Immune System Diseases
Benzalkonium Compounds
Tetrahydrozoline
Bimatoprost
Dinoprost
Dinoprost tromethamine
Anti-Infective Agents, Local
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Nasal Decongestants
Vasoconstrictor Agents
Cardiovascular Agents
Respiratory System Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Oxytocics

ClinicalTrials.gov processed this record on July 23, 2014