Trial Outcomes & Findings for Dextromethorphan for Diabetic Macular Edema (NCT NCT01441102)

Last Updated: 2020-07-28

Results Overview

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."

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

7 participants

Primary outcome timeframe

Baseline and 6 months

Results posted on

2020-07-28

Participant Flow

Five participant 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.

Participant milestones

Participant milestones
Measure	Dextromethorphan Hydrobromide Dextromethorphan hydrobromide: Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 months.
Overall Study STARTED	7
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Dextromethorphan Hydrobromide Dextromethorphan hydrobromide: Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 months.
Overall Study Adverse Event	1
Overall Study Withdrawal by Subject	2

Baseline Characteristics

Dextromethorphan for Diabetic Macular Edema

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dextromethorphan Hydrobromide n=7 Participants Dextromethorphan hydrobromide: Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 months.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Age, Continuous	58.57 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 6 months

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

Outcome measures

Outcome measures
Measure	Dextromethorphan Hydrobromide n=5 Eyes Dextromethorphan hydrobromide: Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 months.
Percentage Change in Retinal Thickness in the Study Eye at 6 Months Compared to Baseline	-7.89 percentage change in retinal thickness Standard Deviation 15.18

SECONDARY outcome

Timeframe: Baseline and 12 Months

Outcome measures

Outcome measures
Measure	Dextromethorphan Hydrobromide n=4 eyes Dextromethorphan hydrobromide: Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 months.
Percentage Change in Retinal Thickness in the Study Eye at 12 Months Compared to Baseline	6.54 percentage change in retinal thickness Standard Deviation 26.96

SECONDARY outcome

Timeframe: Baseline and 18 Months

Outcome measures

Outcome measures
Measure	Dextromethorphan Hydrobromide n=4 eyes Dextromethorphan hydrobromide: Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 months.
Percentage Change in Retinal Thickness in the Study Eye at 18 Months Compared to Baseline	-0.99 percentage change in retinal thickness Standard Deviation 19.11

SECONDARY outcome

Timeframe: Baseline and 24 Months

Outcome measures

Outcome measures
Measure	Dextromethorphan Hydrobromide n=4 eyes Dextromethorphan hydrobromide: Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 months.
Percentage Change in Retinal Thickness in the Study Eye at 24 Months Compared to Baseline	-7.44 percentage change in retinal thickness Standard Deviation 18.33

SECONDARY outcome

Timeframe: Baseline and 6 Months

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

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.

Outcome measures

Outcome measures
Measure	Dextromethorphan Hydrobromide n=5 Eyes Dextromethorphan hydrobromide: Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 months.
Change in Best-corrected Visual Acuity (BCVA) in the Study Eye at 6 Months Compared to Baseline	0.60 ETDRS letters Standard Deviation 11.44

SECONDARY outcome

Timeframe: Baseline and 12 Months

Outcome measures

Outcome measures
Measure	Dextromethorphan Hydrobromide n=4 Eyes Dextromethorphan hydrobromide: Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 months.
Change in Best-corrected Visual Acuity (BCVA) in the Study Eye at 12 Months Compared to Baseline	1.50 ETDRS letters Standard Deviation 15.02

SECONDARY outcome

Timeframe: Baseline and 18 Months

Outcome measures

Outcome measures
Measure	Dextromethorphan Hydrobromide n=4 Eyes Dextromethorphan hydrobromide: Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 months.
Change in Best-corrected Visual Acuity (BCVA) in the Study Eye at 18 Months Compared to Baseline	4.00 ETDRS letters Standard Deviation 10.74

SECONDARY outcome

Timeframe: Baseline and 24 Months

Outcome measures

Outcome measures
Measure	Dextromethorphan Hydrobromide n=4 Eyes Dextromethorphan hydrobromide: Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 months.
Change in Best-corrected Visual Acuity (BCVA) in the Study Eye at 24 Months Compared to Baseline	5.50 ETDRS letters Standard Deviation 12.58

SECONDARY outcome

Timeframe: Baseline and 6 Months

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).

Outcome measures

Outcome measures
Measure	Dextromethorphan Hydrobromide n=5 eyes Dextromethorphan hydrobromide: Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 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	4 eyes

SECONDARY outcome

Timeframe: Baseline and 12 Months

Outcome measures

Outcome measures
Measure	Dextromethorphan Hydrobromide n=4 eyes Dextromethorphan hydrobromide: Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 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	3 eyes

SECONDARY outcome

Timeframe: Baseline and 18 Months

Outcome measures

Outcome measures
Measure	Dextromethorphan Hydrobromide n=4 eyes Dextromethorphan hydrobromide: Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 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	2 eyes

SECONDARY outcome

Timeframe: Baseline and 24 Months

Outcome measures

Outcome measures
Measure	Dextromethorphan Hydrobromide n=4 eyes Dextromethorphan hydrobromide: Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 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	4 eyes

SECONDARY outcome

Timeframe: Baseline and 6 Months

Microperimetry was used to assess macular sensitivity.

Outcome measures

Outcome measures
Measure	Dextromethorphan Hydrobromide n=5 eyes Dextromethorphan hydrobromide: Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 months.
Changes in Mean Macular Sensitivity in the Study Eye at 6 Months Compared to Baseline	-2.1 dB Standard Deviation 3.10

SECONDARY outcome

Timeframe: Baseline and 12 Months

Microperimetry was used to assess macular sensitivity.

Outcome measures

Outcome measures
Measure	Dextromethorphan Hydrobromide n=4 eyes Dextromethorphan hydrobromide: Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 months.
Changes in Mean Macular Sensitivity in the Study Eye at 12 Months Compared to Baseline	-3.7 dB Standard Deviation 3.44

SECONDARY outcome

Timeframe: Baseline and 18 Months

Microperimetry was used to assess macular sensitivity.

Outcome measures

Outcome measures
Measure	Dextromethorphan Hydrobromide n=4 eyes Dextromethorphan hydrobromide: Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 months.
Changes in Mean Macular Sensitivity in the Study Eye at 18 Months Compared to Baseline	-4.9 dB Standard Deviation 3.97

SECONDARY outcome

Timeframe: Baseline and 24 Months

Microperimetry was used to assess macular sensitivity.

Outcome measures

Outcome measures
Measure	Dextromethorphan Hydrobromide n=2 eyes Dextromethorphan hydrobromide: Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 months.
Changes in Mean Macular Sensitivity in the Study Eye at 24 Months Compared to Baseline	-3.9 dB Standard Deviation 3.54

SECONDARY outcome

Timeframe: Duration of the study, up to 24 months

Outcome measures

Outcome measures
Measure	Dextromethorphan Hydrobromide n=7 Participants Dextromethorphan hydrobromide: Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 months.
Number of Participants Withdrawn From the Study Therapy Due to Vision Loss or Adverse Events	1 participants

Adverse Events

Dextromethorphan Hydrobromide

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dextromethorphan Hydrobromide n=7 participants at risk Dextromethorphan hydrobromide: Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 months.
Eye disorders Vitreous haemorrhage	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant

Other adverse events

Other adverse events
Measure	Dextromethorphan Hydrobromide n=7 participants at risk Dextromethorphan hydrobromide: Participants instructed to take 60 mg dextromethorphan capsules orally two times a day for 24 months.
Eye disorders Vitreous haemorrhage	28.6% 2/7 • Number of events 2 • Duration of the study, up to 24 months per participant
General disorders Malaise	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
General disorders Fatigue	42.9% 3/7 • Number of events 3 • Duration of the study, up to 24 months per participant
Renal and urinary disorders Nephrolithiasis	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Eye disorders Photophobia	14.3% 1/7 • Number of events 2 • Duration of the study, up to 24 months per participant
Respiratory, thoracic and mediastinal disorders Cough	14.3% 1/7 • Number of events 2 • Duration of the study, up to 24 months per participant
Skin and subcutaneous tissue disorders Blister	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Musculoskeletal and connective tissue disorders Myalgia	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Injury, poisoning and procedural complications Laceration	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Infections and infestations Tooth infection	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Infections and infestations Furuncle	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Infections and infestations Viral infection	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Nervous system disorders Dizziness	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Metabolism and nutrition disorders Hypoglycaemia	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Infections and infestations Upper respiratory tract infection	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
General disorders Feeling jittery	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Investigations Renal function test abnormal	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Blood and lymphatic system disorders Anaemia	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Eye disorders Dry eye	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Gastrointestinal disorders Diarrhoea	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Eye disorders Episcleritis	14.3% 1/7 • Number of events 2 • Duration of the study, up to 24 months per participant
Injury, poisoning and procedural complications Fall	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Injury, poisoning and procedural complications Arthropod Bite	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Skin and subcutaneous tissue disorders Dry skin	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Eye disorders Iridocyclitis	14.3% 1/7 • Number of events 2 • Duration of the study, up to 24 months per participant
Injury, poisoning and procedural complications Limb injury	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Eye disorders Eye Pain	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Respiratory, thoracic and mediastinal disorders Sinus congestion	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Skin and subcutaneous tissue disorders Skin disorder	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Eye disorders Vision blurred	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant
Eye disorders Vitreous floaters	14.3% 1/7 • Number of events 1 • Duration of the study, up to 24 months per participant

Additional Information

Catherine Cukras, MD, PhD, Principal Investigator, NEI

National Institutes of Health

Phone: 301-435-5061

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place