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

NCT03384524 | Withdrawn Phase 1 DMC

• 1 other identifier: The BEAT DME Study
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Diabetic Macular Edema

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Progression of non-central DME compared to central DME

  14 months

• Progression of non-central DME compared to central DME

  14 months

• Change in retinal density

  14 months

• Foveal avascular changes

  14 months

Study Arms (2)

Combination regiment

ACTIVE COMPARATOR

A combination regiment of Bromocriptine (2.5 mg/day), Metoprolol (25 mg/day) and Tamsulosin (0.4 mg/day)

Drug: Bromocriptine 2.5 MG; Drug: Metoprolol 25 MG; Drug: Tamsulosin 0.4 MG

Placebo

PLACEBO COMPARATOR

Three placebo pills, matching the external appearance of active drugs

Other: Placebo

Interventions

Bromocriptine 2.5 MG DRUG

Administered daily

Also known as: Bromocriptine Mesylate

Combination regiment

Metoprolol 25 MG DRUG

Administered daily

Also known as: Metoprolol Tartrate

Combination regiment

Tamsulosin 0.4 MG DRUG

Administered daily

Also known as: Tamsulosin HCL, Tamsulosin Hydrochloride

Combination regiment

Placebo OTHER

Three pills, matching active drugs to be administered daily

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Andrew Moshfeghi, MD, MBA: lead
• Case Western Reserve University: collaborator

MeSH Terms

Interventions

Bromocriptine; Metoprolol; Tamsulosin

Intervention Hierarchy (Ancestors)

Ergotamines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Ergolines; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Benzenesulfonamides; Sulfonamides; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds

Study Officials

• Andrew A. Moshfeghi, MD, MBA

  Associate Professor of Ophthalmology; Director of Vitreoretinal Surgery and Medical Retina Fellowship; Director of Clinical Trials Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Ophthalmology, Director of Vitreoretinal Surgery Fellowship and Medical Retina Fellowship, Director of Clinical Trials Unit

Study Record Dates

• First Submitted: December 15, 2017
• First Posted: December 27, 2017
• Study Start: March 1, 2018
• Primary Completion: May 1, 2019
• Study Completion: May 1, 2019
• Last Updated: April 1, 2019

Record last verified: 2019-03