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

NCT01120899 | Completed Phase 1 Results

• 2 other identifiers: 10009810-EI-0098
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to investigate the safety and efficacy of minocycline as a microglia inhibitor in individuals with diabetic macular edema (DME).

Conditions

Diabetic Macular Edema

Keywords

Diabetic Macular Edema; Microglia; Minocycline; Diabetes

Outcome Measures

Primary Outcomes (1)

• 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

  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."

  6 months

Secondary Outcomes (16)

• Change in BCVA in the Study Eye at 6 Months Compared to Baseline

  Baseline and 6 Months

• Change in BCVA in the Study Eye at 12 Months Compared to Baseline

  Baseline and 12 Months

• Change in BCVA in the Study Eye at 18 Months Compared to Baseline

  Baseline and 18 Months

• Change in BCVA in the Study Eye at 24 Months Compared to Baseline

  Baseline and 24 Months

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

  Baseline and 6 Months

Study Arms (1)

Minocycline

EXPERIMENTAL

Drug: Minocycline

Interventions

Minocycline DRUG

Participants take 100 mg minocycline pills twice daily for 24 months.

Also known as: Dynacin; serial number 73419626, Minocin; serial number 72309825, Minocin PAC, Myrac; serial number 76589055, Solodyn; serial number 78883462, Vectrin; serial number 78188505

Minocycline

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 (see Appendix 1 for definition) 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 (see Appendix 1 for definition) 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 (based on the half life of minocycline which is 11-22 hours). 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). \*Oral birth control pills must be used with caution as minocycline decreases the effectiveness of some oral contraceptives. Participants already taking oral contraceptives may continue to use them, but must agree to use at least one other method of birth control while on study.
• Participants must agree to notify the study investigator or coordinator if any of their doctors initiate a new medication 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). Refer to Appendix 2 for grading.
• 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.

You may not qualify if:

• Participant is in another investigational study and actively receiving study therapy.
• 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 minocycline or any drug in the tetracycline family.
• Participant is taking any medication that could adversely interact with minocycline such as methoxyflurane.
• 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, 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.
• Participant has a history of thyroid cancer.
• Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity score between 78 and 39 letters (i.e., between 20/32 and 20/200).
• Definite retinal thickening due to diabetic macular edema based on clinical exam involving the center of the macula that is not refractory to further therapy as based on the investigator's clinical judgment.

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

• Cukras CA, Petrou P, Chew EY, Meyerle CB, Wong WT. Oral minocycline for the treatment of diabetic macular edema (DME): results of a phase I/II clinical study. Invest Ophthalmol Vis Sci. 2012 Jun 22;53(7):3865-74. doi: 10.1167/iovs.11-9413.

  PMID: 22589436 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

cyclopia sequence; Diabetes Mellitus

Interventions

Minocycline

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

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
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 8, 2010
• First Posted: May 11, 2010
• Study Start: April 1, 2010
• Primary Completion: August 1, 2011
• Study Completion: February 1, 2013
• Last Updated: October 17, 2014
• Results First Posted: September 6, 2012

Record last verified: 2014-10

Locations

US (1)