Trial Outcomes & Findings for A Pilot Study for the Evaluation of Minocycline as a Microglia Inhibitor in the Treatment of Diabetic Macular Edema (NCT NCT01120899)

NCT ID: NCT01120899

Last Updated: 2014-10-17

Results Overview

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. 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

6 participants

Primary outcome timeframe

6 months

Results posted on

2014-10-17

Participant Flow

Participant milestones

Participant milestones
Measure
Minocycline
Participants take an oral dose of 100 mg of minocycline twice daily for 24 months.
Overall Study
STARTED
6
Overall Study
Month 6
5
Overall Study
Month 12
3
Overall Study
Month 18
3
Overall Study
COMPLETED
3
Overall Study
NOT COMPLETED
3

Reasons for withdrawal

Reasons for withdrawal
Measure
Minocycline
Participants take an oral dose of 100 mg of minocycline twice daily for 24 months.
Overall Study
Withdrawal by Subject
3

Baseline Characteristics

A Pilot Study for the Evaluation of Minocycline as a Microglia Inhibitor in the Treatment of Diabetic Macular Edema

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Minocycline
n=6 Participants
Participants take an oral dose of 100 mg of minocycline twice daily for 24 months.
Age, Categorical
<=18 years
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
4 Participants
n=5 Participants
Age, Categorical
>=65 years
2 Participants
n=5 Participants
Age, Continuous
63.8 years
STANDARD_DEVIATION 9.5 • n=5 Participants
Sex: Female, Male
Female
2 Participants
n=5 Participants
Sex: Female, Male
Male
4 Participants
n=5 Participants
Region of Enrollment
United States
6 participants
n=5 Participants

PRIMARY outcome

Timeframe: 6 months

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. 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."

Outcome measures

Outcome measures
Measure
Minocycline
n=5 Eyes
Participants take an oral dose of 100 mg of minocycline twice daily for 24 months.
Number of Study Eyes Demonstrating an Increase or Decrease in Best-corrected Visual Acuity (BCVA) of 15 or More Early Treatment Diabetic Retinopathy Study (ETDRS) Letters at 6 Months Compared to Baseline
1 Eyes

SECONDARY outcome

Timeframe: Baseline and 6 Months

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. 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."

Outcome measures

Outcome measures
Measure
Minocycline
n=5 Eyes
Participants take an oral dose of 100 mg of minocycline twice daily for 24 months.
Change in BCVA in the Study Eye at 6 Months Compared to Baseline
5.8 ETDRS Letters
Standard Deviation 5.4

SECONDARY outcome

Timeframe: Baseline and 12 Months

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. 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."

Outcome measures

Outcome measures
Measure
Minocycline
n=3 Eyes
Participants take an oral dose of 100 mg of minocycline twice daily for 24 months.
Change in BCVA in the Study Eye at 12 Months Compared to Baseline
8.0 ETDRS Letters
Standard Deviation 8.9

SECONDARY outcome

Timeframe: Baseline and 18 Months

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
Minocycline
n=3 Eyes
Participants take an oral dose of 100 mg of minocycline twice daily for 24 months.
Change in BCVA in the Study Eye at 18 Months Compared to Baseline
9.0 ETDRS letters
Standard Deviation 4.0

SECONDARY outcome

Timeframe: Baseline and 24 Months

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
Minocycline
n=3 Eyes
Participants take an oral dose of 100 mg of minocycline twice daily for 24 months.
Change in BCVA in the Study Eye at 24 Months Compared to Baseline
9.3 ETDRS letters
Standard Deviation 6.8

SECONDARY outcome

Timeframe: 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."

Outcome measures

Outcome measures
Measure
Minocycline
n=5 Eyes
Participants take an oral dose of 100 mg of minocycline twice daily for 24 months.
Percentage Change in Retinal Thickness in the Study Eye at 6 Months Compared to Baseline
-8.1 percentage change
Standard Deviation 14.6

SECONDARY outcome

Timeframe: Baseline and 12 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.

Outcome measures

Outcome measures
Measure
Minocycline
n=3 Eyes
Participants take an oral dose of 100 mg of minocycline twice daily for 24 months.
Percentage Change in Retinal Thickness in the Study Eye at 12 Months Compared to Baseline
-12.35 percentage change in retinal thickness
Standard Deviation 1.21

SECONDARY outcome

Timeframe: Baseline and 18 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.

Outcome measures

Outcome measures
Measure
Minocycline
n=3 Eyes
Participants take an oral dose of 100 mg of minocycline twice daily for 24 months.
Percentage Change in Retinal Thickness in the Study Eye at 18 Months Compared to Baseline
-20.09 percentage change in retinal thickness
Standard Deviation 10.65

SECONDARY outcome

Timeframe: Baseline and 24 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.

Outcome measures

Outcome measures
Measure
Minocycline
n=3 Eyes
Participants take an oral dose of 100 mg of minocycline twice daily for 24 months.
Percentage Change in Retinal Thickness in the Study Eye at 24 Months Compared to Baseline
-20.83 percentage change in retinal thickness
Standard Deviation 4.62

SECONDARY outcome

Timeframe: 6 Months

Fluorescein angiography (FA) images from both eyes in each participant 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)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD). 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."

Outcome measures

Outcome measures
Measure
Minocycline
n=5 Eyes
Participants take an oral dose of 100 mg of minocycline twice daily 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
5 Eyes

SECONDARY outcome

Timeframe: 12 Months

Fluorescein angiography (FA) images from both eyes in each participant 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)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD). 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."

Outcome measures

Outcome measures
Measure
Minocycline
n=3 Eyes
Participants take an oral dose of 100 mg of minocycline twice daily 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: 18 Months

Fluorescein angiography (FA) images from both eyes in each participant 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)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD). 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."

Outcome measures

Outcome measures
Measure
Minocycline
n=3 Eyes
Participants take an oral dose of 100 mg of minocycline twice daily 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
3 Eyes

SECONDARY outcome

Timeframe: 24 Months

Fluorescein angiography (FA) images from both eyes in each participant 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)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD). 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."

Outcome measures

Outcome measures
Measure
Minocycline
n=3 Eyes
Participants take an oral dose of 100 mg of minocycline twice daily 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
3 Eyes

SECONDARY outcome

Timeframe: 6 Months

Fluorescein angiography (FA) images from both eyes in each participant 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)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD). 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."

Outcome measures

Outcome measures
Measure
Minocycline
n=5 Eyes
Participants take an oral dose of 100 mg of minocycline twice daily for 24 months.
Number of Fellow 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: 12 Months

Fluorescein angiography (FA) images from both eyes in each participant 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)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD). 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."

Outcome measures

Outcome measures
Measure
Minocycline
n=3 Eyes
Participants take an oral dose of 100 mg of minocycline twice daily for 24 months.
Number of Fellow Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 12 Months Compared to Baseline
1 Eyes

SECONDARY outcome

Timeframe: 18 Months

Fluorescein angiography (FA) images from both eyes in each participant 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)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD). 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."

Outcome measures

Outcome measures
Measure
Minocycline
n=3 Eyes
Participants take an oral dose of 100 mg of minocycline twice daily for 24 months.
Number of Fellow 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: 24 Months

Fluorescein angiography (FA) images from both eyes in each participant 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)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD). 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."

Outcome measures

Outcome measures
Measure
Minocycline
n=3 Eyes
Participants take an oral dose of 100 mg of minocycline twice daily for 24 months.
Number of Fellow Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 24 Months Compared to Baseline
1 Eyes

Adverse Events

Minocycline

Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Minocycline
n=6 participants at risk
Participants take an oral dose of 100 mg of minocycline twice daily for 24 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Laryngeal cancer
16.7%
1/6 • Number of events 1 • 18 months

Other adverse events

Other adverse events
Measure
Minocycline
n=6 participants at risk
Participants take an oral dose of 100 mg of minocycline twice daily for 24 months.
Gastrointestinal disorders
Abdominal pain upper
16.7%
1/6 • Number of events 1 • 18 months
Eye disorders
Blepharitis
16.7%
1/6 • Number of events 1 • 18 months
Investigations
Blood albumin decreased
16.7%
1/6 • Number of events 1 • 18 months
Investigations
Blood glucose increased
33.3%
2/6 • Number of events 2 • 18 months
Investigations
Blood magnesium decreased
16.7%
1/6 • Number of events 1 • 18 months
Investigations
Blood thyroid stimulating hormone abnormal
16.7%
1/6 • Number of events 1 • 18 months
Gastrointestinal disorders
Diarrhoea
33.3%
2/6 • Number of events 5 • 18 months
Nervous system disorders
Dizziness
16.7%
1/6 • Number of events 1 • 18 months
Nervous system disorders
Dysgeusia
16.7%
1/6 • Number of events 1 • 18 months
General disorders
Fatigue
16.7%
1/6 • Number of events 1 • 18 months
Infections and infestations
Gastroenteritis viral
16.7%
1/6 • Number of events 1 • 18 months
Investigations
Glycosylated haemoglobin increased
16.7%
1/6 • Number of events 1 • 18 months
Investigations
Haemoglobin decreased
33.3%
2/6 • Number of events 2 • 18 months
Nervous system disorders
Headache
16.7%
1/6 • Number of events 1 • 18 months
Metabolism and nutrition disorders
Hypercholesterolaemia
16.7%
1/6 • Number of events 1 • 18 months
Musculoskeletal and connective tissue disorders
Muscle spasms
16.7%
1/6 • Number of events 1 • 18 months
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
16.7%
1/6 • Number of events 1 • 18 months
Infections and infestations
Nasopharyngitis
16.7%
1/6 • Number of events 1 • 18 months
Renal and urinary disorders
Nephrolithiasis
16.7%
1/6 • Number of events 1 • 18 months
General disorders
Oedema peripheral
16.7%
1/6 • Number of events 1 • 18 months
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
16.7%
1/6 • Number of events 1 • 18 months
Cardiac disorders
Palpitations
16.7%
1/6 • Number of events 1 • 18 months
Skin and subcutaneous tissue disorders
Rash
16.7%
1/6 • Number of events 1 • 18 months
Skin and subcutaneous tissue disorders
Skin ulcer
16.7%
1/6 • Number of events 1 • 18 months
Infections and infestations
Viral infection
16.7%
1/6 • Number of events 1 • 18 months
Reproductive system and breast disorders
Vulvovaginal pruritus
16.7%
1/6 • Number of events 2 • 18 months
Investigations
White blood cell count increased
16.7%
1/6 • Number of events 1 • 18 months
Eye disorders
Meibomianitis
16.7%
1/6 • Number of events 1 • 18 months
Gastrointestinal disorders
Abdominal discomfort
16.7%
1/6 • Number of events 1 • 18 months
Infections and infestations
Tinea pedis
16.7%
1/6 • Number of events 1 • 18 months
Investigations
Blood pressure increased
16.7%
1/6 • Number of events 1 • 18 months
Skin and subcutaneous tissue disorders
Pruritis
16.7%
1/6 • Number of events 2 • 18 months
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
33.3%
2/6 • Number of events 3 • 18 months

Additional Information

Catherine Cukras, MD, PhD, Principal Investigator, NEI

National Institutes of Health

Phone: 301-435-5061

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place