Evaluation of Bromocriptine, Metoprolol and Tamsulosin in Eyes With Non-Central DME

Study Overview
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Brief Summary
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This phase I/II trial is designed to provide proof of concept evidence that combination therapy can have a beneficial effect on DME and possibly prevent increases in retinal volume or progression of non-central DME into the central subfield of the macula. If a beneficial effect is apparent in this phase I/II study involving a relatively small sample size and short follow-up period, its results could be used to in plan future phase III trials. We believe this study will be the first to show that a systems pharmacology approach can successfully address diabetic macular edema, and thus revolutionize the treatment of complex retinal diseases for which there are a paucity of effective treatment options.

Official Title
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A Phase I/II Evaluation of Bromocriptine, Metoprolol and Tamsulosin Combination Therapy in Eyes With Non-Central Diabetic Macular Edema

Conditions
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Diabetic Macular Edema

Intervention / Treatment
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* Drug: Bromocriptine 2.5 MG
* Drug: Metoprolol 25 MG
* Drug: Tamsulosin 0.4 MG
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years Type 1 or type 2 diabetes mellitus Best corrected visual acuity using the early treatment diabetic retinopathy study (ETDRS) visual acuity test letter score ≥ 74 (i.e., 20/32 or better) within 30 days of enrollment. On clinical exam, definite retinal thickening due to DME within 3,000 μm of the center of the macula but not involving the 500 μm central subfield. Thickened non-central macular subfields on the spectral domain OCT macular map Central subfield thickness within threshold definition for normal central subfield thickness No focal/grid laser within the last 6 months or other treatment for DME within the last 4 months. Pseudophakia Exclusion Criteria: Patients with active proliferative diabetic retinopathy Pan retinal photocoagulation within the last 12 months of study initiation A condition that, in the opinion of the investigator, would preclude participation in the study, e.g., unstable medical status including blood pressure, cardiovascular disease, and glycemic control. Subjects experiencing poor glycemic control who, within the last 4 months, initiated intensive insulin treatment (a pump or multiple daily injections) or plan to do so in the next 4 months. Use of systemic corticosteroids or anti-VEGF (vascular endothelial growth factor) therapy. Participation in an investigational trial that involves treatment with any drug within 30 days of randomization that has not received regulatory approval at the time of study entry. Note: study participants cannot receive another investigational drug while participating in this study. Known allergy or hypersensitivity to any component of the study drugs. Postpartum women with a history of coronary artery disease or other severe cardiovascular conditions (a bromocriptine contraindication). Planned glaucoma surgery (floppy iris syndrome associated with tamsulosin therapy). Blood pressure > 180/110 mmHg (systolic above 180 or diastolic above 110 mmHg). If blood pressure is brought below 180/110 by anti-hypertensive treatment, an individual can become eligible. Subjects with second or third degree heart block (metoprolol contraindication). Subjects with asthma or other bronchospastic disease (metoprolol precaution). Individuals currently taking one of the study medications or a medication in the same therapeutic class (beta receptor antagonists, alpha-1 receptor antagonists, or bromocriptine). Participants expecting to move out of the area of the clinical center to an area not covered by another clinical center during the 12 months of the study. For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 12 months. Women who are potential study participants should be questioned about the potential for pregnancy. Investigator judgment will be used to determine when a pregnancy test is needed.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Combination regiment<br>A combination regiment of Bromocriptine (2.5 mg/day), Metoprolol (25 mg/day) and Tamsulosin (0.4 mg/day) | Drug: Bromocriptine 2.5 MG<br>* Administered daily<br>* Other names: Bromocriptine Mesylate;Drug: Metoprolol 25 MG<br>* Administered daily<br>* Other names: Metoprolol Tartrate;Drug: Tamsulosin 0.4 MG<br>* Administered daily<br>* Other names: Tamsulosin Hydrochloride;|
| Placebo Comparator: Placebo<br>Three placebo pills, matching the external appearance of active drugs | Other: Placebo<br>* Three pills, matching active drugs to be administered daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in retinal volume | Effects of bromocriptine/metoprolol/tamsulosin combination therapy on macular retinal volume compared with placebo in eyes with non-central diabetic macular edema (DME) | 14 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression of non-central DME compared to central DME | Effects of therapy with bromocriptine/metoprolol/tamsulosin on central subfield thickness and compare the progression of non-central DME to central DME as determined by stereoscopic fundus photographs. | 14 months | 
| Progression of non-central DME compared to central DME | Effects of therapy with bromocriptine/metoprolol/tamsulosin on central subfield thickness and compare the progression of non-central DME to central DME as determined by Optical Coherence Tomography (OCT). | 14 months | 
| Change in retinal density | Measured by OCT-angiography | 14 months | 
| Foveal avascular changes | Measured by fluorescein angiography. | 14 months |