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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Drug: Bromocriptine 2.5 MG; Drug: Metoprolol 25 MG; Drug: Tamsulosin 0.4 MG; Other: Placebo

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Combination regiment; A combination regiment of Bromocriptine (2.5 mg/day), Metoprolol (25 mg/day) and Tamsulosin (0.4 mg/day)	Drug: Bromocriptine 2.5 MG; Administered daily; Other Names: Bromocriptine Mesylate; Drug: Metoprolol 25 MG; Administered daily; Other Names: Metoprolol Tartrate; Drug: Tamsulosin 0.4 MG; Administered daily; Other Names: Tamsulosin HCL; Tamsulosin Hydrochloride
PLACEBO_COMPARATOR: Placebo; Three placebo pills, matching the external appearance of active drugs	Other: Placebo; Three pills, matching active drugs to be administered daily

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Andrew Moshfeghi, MD, MBA
• Collaborators: Case Western Reserve University
• Investigators: Principal Investigator: Andrew A. Moshfeghi, MD, MBA, Associate Professor of Ophthalmology; Director of Vitreoretinal Surgery and Medical Retina Fellowship; Director of Clinical Trials Unit

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): March 1, 2018
• Primary Completion (ANTICIPATED): May 1, 2019
• Study Completion (ANTICIPATED): May 1, 2019

Study Registration Dates

• First Submitted: December 15, 2017
• First Submitted That Met QC Criteria: December 19, 2017
• First Posted (ACTUAL): December 27, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 1, 2019
• Last Update Submitted That Met QC Criteria: March 28, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Urological Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Dopamine Agonists; Dopamine Agents; Hormone Antagonists; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Antiparkinson Agents; Anti-Dyskinesia Agents; Tamsulosin; Metoprolol; Bromocriptine
• Other Study ID Numbers: The BEAT DME Study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No