Dextromethorphan for Diabetic Macular Edema

NCT01441102 | Completed Phase 1 Results

• 2 other identifiers: 11024411-EI-0244
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Many people with diabetes have macular edema (swelling) at the back of the eye. Macular edema can cause loss of vision. Studies suggest that inflammation may be involved in the swelling. A drug called dextromethorphan may help prevent the inflammation and the swelling. Dextromethorphan is approved for use as a cough medicine, but it has not been studied to see if it can help in diabetic macular edema. Objectives: To see if dextromethorphan can help treat diabetic macular edema. Eligibility: Individuals at least 18 years of age who have diabetic macular edema in at least one eye. Design:

• This study lasts 2 years, and will require at least 14 visits to the National Eye Institute outpatient clinic. Study visits will be every month for the first 2 months and then every other month. Each visit will take about 2 to 4 hours.
• Participants will be screened with a physical exam, medical history, eye exam, and blood tests. One eye with macular edema will be chosen as the study eye for testing.
• Participants will take dextromethorphan twice a day, about 12 hours apart, for 2 years. A study diary will help keep track of the date, time, and number of pills taken.
• Participants will have study visits once a month for the first 2 months and then every other month for the rest of the study. Each study visit will involve eye exams and blood and urine tests.
• Four months after starting the study medication, participants may have laser surgery or other treatments for the macular edema, if it is needed.

Conditions

Diabetic Macular Edema

Keywords

Diabetic Macular Edema; Microglia; Dextromethorphan

Outcome Measures

Primary Outcomes (1)

• Percentage Change in Retinal Thickness in the Study Eye at 6 Months Compared to Baseline

  Retinal thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue. The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."

  Baseline and 6 months

Secondary Outcomes (16)

• Percentage Change in Retinal Thickness in the Study Eye at 12 Months Compared to Baseline

  Baseline and 12 Months

• Percentage Change in Retinal Thickness in the Study Eye at 18 Months Compared to Baseline

  Baseline and 18 Months

• Percentage Change in Retinal Thickness in the Study Eye at 24 Months Compared to Baseline

  Baseline and 24 Months

• Change in Best-corrected Visual Acuity (BCVA) in the Study Eye at 6 Months Compared to Baseline

  Baseline and 6 Months

• Change in Best-corrected Visual Acuity (BCVA) in the Study Eye at 12 Months Compared to Baseline

  Baseline and 12 Months

Study Arms (1)

Dextromethorphan hydrobromide

EXPERIMENTAL

Drug: Dextromethorphan hydrobromide

Interventions

Dextromethorphan hydrobromide DRUG

Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 months.

Also known as: Delsym, Creomulsion, Benylin

Dextromethorphan hydrobromide

Eligibility Criteria

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

You may qualify if:

• Participant is 18 years of age or older.
• Participant must understand and sign the protocol's informed consent document.
• Female participants of childbearing potential must not be pregnant or breast-feeding, must have a negative urine pregnancy test within 24 hours prior to initiation of study medication and must be willing to undergo urine pregnancy tests throughout the study.
• Female participants of childbearing potential and male participants able to father children must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse or must agree to practice two acceptable methods of contraception throughout the course of the study and for one week after study medication discontinuation. Acceptable methods of contraception include:
• hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring),
• intrauterine device,
• barrier methods (diaphragm, condom) with spermicide, or
• surgical sterilization (hysterectomy or tubal ligation).
• Participant must agree to notify the study investigator or coordinator if any of his/her doctors initiate a new medication during the course of this study.
• Participant must agree not to take medications containing dextromethorphan during the course of this study.
• Participant must have normal renal function and liver function, or have mild abnormalities no greater than grade 1 as defined by the Common Terminology Criteria for Adverse Events v4.0 (CTCAE).
• Participant has a diagnosis of diabetic mellitus (type 1 or type 2). Any one of the following will be considered to be sufficient evidence that diabetes is present:
• Current regular use of insulin for the treatment of diabetes;
• Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes;
• Documented diabetes by American Diabetes Association (ADA) and/or World Health Organization (WHO) criteria.

You may not qualify if:

• Participant is in another investigational study and actively receiving another study medication for diabetic macular edema (DME).
• Participant is unable to comply with study procedures or follow-up visits.
• Participant has a known hypersensitivity to sodium fluorescein dye.
• Participant has a condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control).
• Patients in poor glycemic control who, within the last four months, initiated intensive insulin treatment (a pump or multiple daily injections) or plan to do so in the next four months should not be enrolled.
• Participant has a history of chronic renal failure requiring dialysis or kidney transplant.
• Participant has a history of hepatitis or liver failure.
• Participant has an allergy or hypersensitivity to dextromethorphan or levorphanol.
• Participant is taking or has taken within the last 14 days any medication that could adversely interact with dextromethorphan such as selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase inhibitors (MAOIs) including but not limited to the following: almotriptan; amitriptyline; amoxapine; bromocriptine; buspirone; cabergoline; citalopram; clomipramine; desipramine; desvenlafaxine; dihydroergotamine; doxepin; duloxetine; eletriptan; ergoloid mesylates; ergotamine; escitalopram; fluoxetine; fluvoxamine; frovatriptan; imipramine; isocarboxazid; linezolid; lithium; maprotiline; meperidine; methylergonovine; milnacipran; mirtazapine; moclobemide; naratriptan; nefazodone; nortriptyline; paroxetine; phenelzine; procarbazine; promethazine; protriptyline; rasagiline; rizatriptan; SAMe (S-adenosylmethionine); selegiline; sertraline; sibutramine; St. Johns wort; sumatriptan; tapentadol; tramadol; tranylcypromine; trazodone; trimipramine; tryptophan; venlafaxine; vilazodone; zolmitriptan.
• Participant has a blood pressure of \> 180/110 (systolic above 180 OR diastolic above 110).
• If blood pressure is brought below 180/110 by anti-hypertensive treatment, a patient can become eligible.
• Participant has a history of treatment with systemic anti-vascular endothelial growth factor (VEGF) agents or steroids within three months prior to study entry.
• Best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) score of 34 letters or better (i.e., 20/200 or better).
• Definite retinal thickening due to diabetic macular edema, based on clinical examination, that is not refractory to further therapy as based on the investigator's clinical judgment.
• Retinal thickening due to DME within 3000 μm of the center of the macula, as measured by Spectral optical coherence tomography (OCT).

Sponsors & Collaborators

• National Eye Institute (NEI): lead
• The Emmes Company, LLC: collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Kempen JH, O'Colmain BJ, Leske MC, Haffner SM, Klein R, Moss SE, Taylor HR, Hamman RF; Eye Diseases Prevalence Research Group. The prevalence of diabetic retinopathy among adults in the United States. Arch Ophthalmol. 2004 Apr;122(4):552-63. doi: 10.1001/archopht.122.4.552.

  PMID: 15078674 BACKGROUND

• Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema. Ophthalmology. 1984 Dec;91(12):1464-74. doi: 10.1016/s0161-6420(84)34102-1.

  PMID: 6521986 BACKGROUND

• Ferris FL 3rd, Patz A. Macular edema: a major complication of diabetic retinopathy. Trans New Orleans Acad Ophthalmol. 1983;31:307-16. No abstract available.

  PMID: 6623578 BACKGROUND

• Valent DJ, Wong WT, Chew EY, Cukras CA. Oral Dextromethorphan for the Treatment of Diabetic Macular Edema: Results From a Phase I/II Clinical Study. Transl Vis Sci Technol. 2018 Dec 17;7(6):24. doi: 10.1167/tvst.7.6.24. eCollection 2018 Nov.

  PMID: 30584490 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

Dextromethorphan; Diphenhydramine

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Ethylamines; Amines; Organic Chemicals; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Catherine Cukras, MD, PhD, Principal Investigator, NEI
• Organization: National Institutes of Health

cukrasc@nei.nih.gov

301-435-5061

Study Officials

• Catherine A Cukras, MD, PhD

  National Eye Institute (NEI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2011
• First Posted: September 27, 2011
• Study Start: August 1, 2011
• Primary Completion: June 1, 2014
• Study Completion: December 1, 2015
• Last Updated: July 28, 2020
• Results First Posted: June 8, 2015

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)