Diabetic Macular EdemaPhase 1/2MiDME2NCT01441102

Dextromethorphan for Diabetic Macular Edema

A Phase 1/2 study testing Dextromethorphan hydrobromide in people with Diabetic Macular Edema, run by National Eye Institute (NEI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Diabetic Macular Edema
What is being tested?: Dextromethorphan hydrobromide
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 7 participants
Where: 1 siteUnited States
Study dates: Aug 2011to Dec 2015
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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,

Show all 19Show fewer

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.
Participant has documented hemoglobin A1C 12% or less within one month of baseline.
Participants with elevated hemoglobin A1C but within the 12% or less cutoff will undergo appropriate evaluation, and unstable patients will be excluded according to the investigator's best medical judgment.
Participant agrees to refrain from consuming grapefruit juice, grapefruits and Seville oranges at any time while s/he is enrolled in this study.
Participant has at least one eye that meets the study eye criteria listed below.

Who cannot join

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.

Show all 36Show fewer

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.
Study Eye Inclusion Criteria
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).
Media clarity, pupillary dilation and patient cooperation sufficient for adequate fundus photographs.
Study Eye Exclusion Criteria
Macular edema is considered to be due to a cause other than diabetic macular edema.
An eye should not be considered eligible if:
The macular edema is considered to be related to cataract extraction; or
Clinical exam and/or OCT suggest that vitreoretinal interface disease (e.g., a taut posterior hyaloid or epiretinal membrane) is the primary cause of the macular edema.
An ocular condition is present such that, in the opinion of the investigator, visual acuity would not improve from resolution of macular edema (e.g., foveal atrophy, pigmentary changes, dense subfoveal hard exudates, non-retinal condition).
An ocular condition is present (other than diabetic retinopathy (DR) that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (e.g., vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, Irvine-Gass Syndrome, etc.).
Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by three lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal).
History of panretinal scatter photocoagulation (PRP) within four months prior to study entry.
History of prior pars plana vitrectomy within six months prior to study entry.
History of major ocular surgery (including cataract extraction, scleral buckle, any intraocular surgery, etc.) within three months prior to study entry.
History of Yttrium aluminium garnet (YAG) capsulotomy performed within two months prior to study entry.
History of treatment within three months prior to enrollment with any drug that has not received regulatory approval at the time of study entry, such as intravitreal or periocular steroids or intravitreal anti-VEGF agents.
Choice of Study Eye in Cases of Bilateral Disease
If both eyes of a participant meet the criteria described above, the following will be used to determine the study eye:
If one eye is treatment-naïve and the other is not, the treatment-naïve eye will be chosen as the study eye.
If both eyes are treatment-naïve, the eye with the better visual acuity will be chosen as the study eye.
If both eyes are treatment-naïve and are equivalent, the choice of study eye will be determined at the investigator's discretion after consultation with the participant.
If both eyes have been previously treated, the choice of study eye will be determined at the investigator's discretion after consultation with the participant.

Trial locations and contacts

1 site in 1 country.

United States1 site

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Pilot Phase I/II Study for the Evaluation of Dextromethorphan as a Microglia Inhibitor in the Treatment of Diabetic Macular Edema (MiDME2)

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.

Read the detailed description

Objective:

Diabetic retinopathy (DR) is one of the leading causes of blindness in the United States. A frequent manifestation of DR is diabetic macular edema (DME) for which the only proven treatment is laser photocoagulation. In the retina, microglia are capable of migrating through the retina to sites of inflammation to associate closely with neurons and the vasculature, and are key cellular players in the mediation of processes of chronic inflammation implicated in DME. For these reasons, microglia represent a promising cellular target for forms of therapy that limit the deleterious inflammatory changes found in DR. The objective of this study is to investigate the safety and efficacy of dextromethorphan as a microglia inhibitor in participants with DME.

Study Population:

Eligibility criteria include presence of diabetic retinopathy with retinal thickening due to diabetic macular edema within 3000 μm of the center of the macula as measured by optical coherence tomography (OCT), and visual acuity better than 20/200 in the study eye.

Design:

Five participants will be initially enrolled in this unmasked pilot study. However, up to an additional three participants may be enrolled to account for participants who withdraw from the study prior to receipt of six months of study treatment. Participants will take an oral dose of 60 mg of dextromethorphan twice daily for 24 months. During each visit, participants will have their visual acuity measured and will undergo OCT testing to measure retinal thickness. Beginning at the Month 4 visit, participants will be assessed for worsening disease defined as loss of ≥ 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters of vision compared to baseline or a ≥ 50% increase in total central retinal thickness as measured by OCT. Individual participants deemed to have worsening disease may stay on the study and continue to receive study medication, but will be allowed to receive focal laser therapy for any amenable leaking microaneurysms and/or anti-vascular endothelial growth factor (VEGF) intravitreal injections (such as bevacizumab or ranibizumab) at the discretion of the treating physician. Additionally, beginning at the Month 6 visit, participants will be eligible for treatment, with either focal laser or anti-VEGF injections if they have center-involving macular edema.

Outcome Measures:

The primary outcome is the change in retinal thickness measured by OCT at 6 months compared to baseline. Secondary outcomes include the change in retinal thickness as measured by OCT at 12, 18 and 24 months compared to baseline, change in best-corrected visual acuity (BCVA) at 6, 12, 18 and 24 months compared to baseline, change in mean macular sensitivity as measured by microperimetry at 6, 12, 18 and 24 months compared to baseline, as well as changes in fluid leakage in the macula as demonstrated by fluorescein angiography at 6, 12, 18 and 24 months compared to baseline. Safety outcomes include the number and severity of systemic and ocular toxicities, and adverse events.

Conditions: Diabetic Macular Edema
Being tested: Dextromethorphan hydrobromide
Keywords: Diabetic Macular Edema, Microglia, Dextromethorphan

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Dextromethorphan hydrobromideDrug
Also called Delsym, Creomulsion, Benylin
Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 months.

Study groups in NCT01441102
Study group	Role	What they receive
Dextromethorphan hydrobromide	Experimental	Not described Receives: Drug: Dextromethorphan hydrobromide

What is being measured

The primary outcome is the main question the study is designed to answer.

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."
Measured: Baseline and 6 months

Secondary outcomes (16)

Percentage Change in Retinal Thickness in the Study Eye at 12 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. Changes in OCT will be calculated using the ETDRS grid. Attention will be directed to changes in retinal thickness as measured by OCT in each of the 9 subfields of the grid.
Measured: Baseline and 12 Months
Percentage Change in Retinal Thickness in the Study Eye at 18 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. Changes in OCT will be calculated using the ETDRS grid. Attention will be directed to changes in retinal thickness as measured by OCT in each of the 9 subfields of the grid.
Measured: Baseline and 18 Months
Percentage Change in Retinal Thickness in the Study Eye at 24 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. Changes in OCT will be calculated using the ETDRS grid. Attention will be directed to changes in retinal thickness as measured by OCT in each of the 9 subfields of the grid.
Measured: Baseline and 24 Months
Change in Best-corrected Visual Acuity (BCVA) in the Study Eye at 6 Months Compared to Baseline
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.
Measured: Baseline and 6 Months
Change in Best-corrected Visual Acuity (BCVA) in the Study Eye at 12 Months Compared to Baseline
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.
Measured: Baseline and 12 Months
Change in Best-corrected Visual Acuity (BCVA) in the Study Eye at 18 Months Compared to Baseline
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.
Measured: Baseline and 18 Months
Change in Best-corrected Visual Acuity (BCVA) in the Study Eye at 24 Months Compared to Baseline
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.
Measured: Baseline and 24 Months
Number of Study Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 6 Months Compared to Baseline
Fluorescein angiography (FA) images were obtained via a standard digital imaging system (OIS, Sacramento, CA) at baseline and at Month 6, Month 12, Month 18, and Month 24. Three retinal specialists independently graded the area of late fluorescein leakage (at approximately 10 minutes) using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD).
Measured: Baseline and 6 Months
Number of Study Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 12 Months Compared to Baseline
Fluorescein angiography (FA) images were obtained via a standard digital imaging system (OIS, Sacramento, CA) at baseline and at Month 6, Month 12, Month 18, and Month 24. Three retinal specialists independently graded the area of late fluorescein leakage (at approximately 10 minutes) using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD).
Measured: Baseline and 12 Months
Number of Study Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 18 Months Compared to Baseline
Fluorescein angiography (FA) images were obtained via a standard digital imaging system (OIS, Sacramento, CA) at baseline and at Month 6, Month 12, Month 18, and Month 24. Three retinal specialists independently graded the area of late fluorescein leakage (at approximately 10 minutes) using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD).
Measured: Baseline and 18 Months
Number of Study Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 24 Months Compared to Baseline
Fluorescein angiography (FA) images were obtained via a standard digital imaging system (OIS, Sacramento, CA) at baseline and at Month 6, Month 12, Month 18, and Month 24. Three retinal specialists independently graded the area of late fluorescein leakage (at approximately 10 minutes) using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD).
Measured: Baseline and 24 Months
Changes in Mean Macular Sensitivity in the Study Eye at 6 Months Compared to Baseline
Microperimetry was used to assess macular sensitivity.
Measured: Baseline and 6 Months
Changes in Mean Macular Sensitivity in the Study Eye at 12 Months Compared to Baseline
Microperimetry was used to assess macular sensitivity.
Measured: Baseline and 12 Months
Changes in Mean Macular Sensitivity in the Study Eye at 18 Months Compared to Baseline
Microperimetry was used to assess macular sensitivity.
Measured: Baseline and 18 Months
Changes in Mean Macular Sensitivity in the Study Eye at 24 Months Compared to Baseline
Microperimetry was used to assess macular sensitivity.
Measured: Baseline and 24 Months
Number of Participants Withdrawn From the Study Therapy Due to Vision Loss or Adverse Events
Measured: Duration of the study, up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2011Dec 2015

First posted27 Sep 2011 (estimated)
Study startAug 2011
Primary completionJun 2014
Study completionDec 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Diabetic Macular EdemaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 7 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01441102
Sponsor's protocol ID: 110244
Other IDs: 11-EI-0244
Acronym: MiDME2
Status last verified: Jan 2017
First submitted: 24 Sep 2011
Last updated: 28 Jul 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Publications

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.
PubMed 15078674
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.
PubMed 6521986
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.
PubMed 6623578
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.
PubMed 30584490

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Blepharoptosis After Repeated Intravitreal Anti-VEGF Injections: A Prospective Study
Blepharoptosis, Age-Related Macular Degeneration
Active, not recruitingPhase 2/3
A Study of 2 Doses of Remigromig (EYE103) Compared With Ranibizumab (0.5 mg) in Participants With DME
Diabetic Macular Edema (DME)
RecruitingPhase 3
A Phase 3 Trial for Intravitreal Injection of 4D-150 in Adults With Diabetic Macular Edema (DME).
Diabetic Macular Edema (DME)
RecruitingPhase 2/3
Surabgene Lomparvovec Administered in the Suprachoroidal Space in Adult Participants With Diabetic Retinopathy Without Center-Involved Diabetic Macular Edema
Diabetic Retinopathy
Active, not recruitingObservational study
Long-Term Follow-up Study of ADVM-022 in DME (INFINITY-EXT)
Diabetic Macular Edema, Diabetic Retinopathy

All Diabetic Macular Edema trials

Study at a glance

From the registry record, last updated by the sponsor on 28 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Pilot Phase I/II Study for the Evaluation of Dextromethorphan as a Microglia Inhibitor in the Treatment of Diabetic Macular Edema (MiDME2)
ClinicalTrials.gov ID: NCT01441102
Acronym / sponsor ID: MiDME2 / 110244
Conditions: Diabetic Macular Edema
Keywords: Diabetic Macular Edema, Microglia, Dextromethorphan
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 7 participants (actual)
Lead sponsor: National Eye Institute (NEI)US National Institutes of Health
Collaborators: The Emmes Company, LLC
Study start: Aug 2011
Primary completion: Jun 2014 (actual)
Study completion: Dec 2015 (actual)
First posted: 27 Sep 2011 (estimated)
Results: Posted 8 Jun 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Detailed description

Objective:

Study Population:

Design:

Outcome Measures:

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Dextromethorphan hydrobromide	Experimental	Drug: Dextromethorphan hydrobromide

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (19 listed)

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:
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.

Key exclusion criteria (36 listed)

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).
Participant has a history of chronic renal failure requiring dialysis or kidney transplant.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Dextromethorphan hydrobromideAlso: Delsym, Creomulsion, BenylinParticipants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 months.	Drug	Dextromethorphan hydrobromide

Primary outcome

Percentage Change in Retinal Thickness in the Study Eye at 6 Months Compared to Baseline
Time frame: Baseline and 6 months
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."

16 secondary outcomes

Percentage Change in Retinal Thickness in the Study Eye at 12 Months Compared to Baseline
Time frame: Baseline and 12 Months
Percentage Change in Retinal Thickness in the Study Eye at 18 Months Compared to Baseline
Time frame: Baseline and 18 Months
Percentage Change in Retinal Thickness in the Study Eye at 24 Months Compared to Baseline
Time frame: Baseline and 24 Months
Change in Best-corrected Visual Acuity (BCVA) in the Study Eye at 6 Months Compared to Baseline
Time frame: Baseline and 6 Months
Change in Best-corrected Visual Acuity (BCVA) in the Study Eye at 12 Months Compared to Baseline
Time frame: Baseline and 12 Months
Change in Best-corrected Visual Acuity (BCVA) in the Study Eye at 18 Months Compared to Baseline
Time frame: Baseline and 18 Months
Change in Best-corrected Visual Acuity (BCVA) in the Study Eye at 24 Months Compared to Baseline
Time frame: Baseline and 24 Months
Number of Study Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 6 Months Compared to Baseline
Time frame: Baseline and 6 Months
Number of Study Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 12 Months Compared to Baseline
Time frame: Baseline and 12 Months
Number of Study Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 18 Months Compared to Baseline
Time frame: Baseline and 18 Months
Number of Study Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 24 Months Compared to Baseline
Time frame: Baseline and 24 Months
Changes in Mean Macular Sensitivity in the Study Eye at 6 Months Compared to Baseline
Time frame: Baseline and 6 Months
Changes in Mean Macular Sensitivity in the Study Eye at 12 Months Compared to Baseline
Time frame: Baseline and 12 Months
Changes in Mean Macular Sensitivity in the Study Eye at 18 Months Compared to Baseline
Time frame: Baseline and 18 Months
Changes in Mean Macular Sensitivity in the Study Eye at 24 Months Compared to Baseline
Time frame: Baseline and 24 Months
Number of Participants Withdrawn From the Study Therapy Due to Vision Loss or Adverse Events
Time frame: Duration of the study, up to 24 months

Results and safety

Results posted to the registry on 8 Jun 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dextromethorphan Hydrobromide	7	4

Primary outcome: Percentage Change in Retinal Thickness in the Study Eye at 6 Months Compared to Baseline

Time frame: Baseline and 6 months. Mean (Standard Deviation). Unit: percentage change in retinal thickness

Measure	Dextromethorphan Hydrobromide n = 5
Value	-7.89 (15.18)

Population analysed: Two participants withdrew from the study prior to the 6-month visit.

16 secondary outcomes are reported in the full results.

Adverse events

Time frame: Duration of the study, up to 24 months per participant. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dextromethorphan Hydrobromide	1 of 7 (14.3%)	6 of 7 (85.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 15078674Kempen 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.
Background: PubMed 6521986Klein 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.
Background: PubMed 6623578Ferris FL 3rd, Patz A. Macular edema: a major complication of diabetic retinopathy. Trans New Orleans Acad Ophthalmol. 1983;31:307-16. No abstract available.
Results publication: PubMed 30584490Valent 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.
NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Individual participant dataSharing planned: No

Related trials for Diabetic Macular Edema

RecruitingObservational study
Blepharoptosis After Repeated Intravitreal Anti-VEGF Injections: A Prospective Study
Blepharoptosis, Age-Related Macular Degeneration
Active, not recruitingPhase 2/3
A Study of 2 Doses of Remigromig (EYE103) Compared With Ranibizumab (0.5 mg) in Participants With DME
Diabetic Macular Edema (DME)
RecruitingPhase 3
A Phase 3 Trial for Intravitreal Injection of 4D-150 in Adults With Diabetic Macular Edema (DME).
Diabetic Macular Edema (DME)
RecruitingPhase 2/3
Surabgene Lomparvovec Administered in the Suprachoroidal Space in Adult Participants With Diabetic Retinopathy Without Center-Involved Diabetic Macular Edema
Diabetic Retinopathy
Active, not recruitingObservational study
Long-Term Follow-up Study of ADVM-022 in DME (INFINITY-EXT)
Diabetic Macular Edema, Diabetic Retinopathy

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Catherine A Cukras, MD, PhD principal investigator

National Eye Institute (NEI)

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Dextromethorphan hydrobromide in people with Diabetic Macular Edema, run by National Eye Institute (NEI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Jun 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage Change in Retinal Thickness in the Study Eye at 6 Months Compared to Baseline (time frame: Baseline and 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01441102, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2020.