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Study of Oral Minocycline in Treating Bilateral Cystoid Macular Edema Associated With Retinitis Pigmentosa

Primary Purpose

Retinitis Pigmentosa

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Minocycline
Sponsored by
National Eye Institute (NEI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Retinitis Pigmentosa focused on measuring Cystoid Macular Edema, Minocycline, Microglia, Retinitis Pigmentosa

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers
  • INCLUSION CRITERIA:
  • To be eligible, the following inclusion criteria must be met, where applicable.
  • Participant must be 12 years of age or older.
  • Participant (or legal guardian) must understand and sign the protocol's informed consent document.
  • Participant must have evidence of retinitis pigmentosa (RP) as defined by characteristic electroretinogram (ERG) responses and visual fields.
  • Participant must be able to swallow pills.
  • Participant must have normal renal function and liver function or have mild abnormalities not above grade 1 as defined by the Common Terminology Criteria for Adverse Events v4.0 (CTCAE).
  • Participant must agree to minimize exposure to sunlight or artificial ultraviolet (UV) rays and to wear protective clothing, sunglasses and sunscreen [minimum sun protection factor (SPF) 15] if s/he must be out in the sun.
  • Any female participant of childbearing potential must have a negative pregnancy test at screening and be willing to undergo pregnancy tests throughout the study.

  • Any female participant of childbearing potential and any male participant 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 at least one week after investigational product (IP) 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).

EXCLUSION CRITERIA:

A participant is not eligible if any of the following exclusion criteria are present.

  • Participant is actively receiving study therapy in another investigational study.
  • Participant is started on (or changed dosage of) topical or systemic carbonic anhydrase inhibitor (CAI) treatment in the 3 months prior to enrollment.
  • Participant is actively receiving systemic steroids or has received systemic steroids in the 3 months prior to enrollment.
  • Any female participant of childbearing potential that is pregnant, breast-feeding or planning to become pregnant during the study.
  • Participant is expected to be unable to comply with study procedures or follow-up visits.
  • Participant has evidence of an ocular disease other than RP in either eye that may confound the outcome of the study (e.g., diabetic retinopathy with 10 or more hemorrhages or microaneurysms, uveitis, pseudovitelliform macular degeneration, severe myopia).
  • Participant is on ocular or systemic medications known to be toxic to the lens, retina or optic nerve (e.g., ethambutol, chloroquine, or hydroxychloroquine).
  • Participant has a condition that would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control) by interfering with the participant s ability to engage in the required protocol evaluation and testing and/or comply with study visits.
  • Participant has a history of chronic renal failure requiring dialysis or kidney transplant.
  • Participant has a history of chronic hepatitis or liver failure.
  • Participant has a history of thyroid cancer.
  • Participant has an allergy or hypersensitivity to minocycline or any drug in the tetracycline family.
  • Participant is currently taking a tetracycline medication.
  • Participant is taking any medication that could adversely interact with minocycline such as methoxyflurane.
  • Participant has a prior history of idiopathic intracranial hypertension.

Sites / Locations

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Minocycline

Arm Description

Oral administration of minocycline

Outcomes

Primary Outcome Measures

Change in Cystoid Macular Edema (CME) Based on Optical Coherence Tomography (OCT) Measurements in the Study Eye at 6 Months Compared to the Average of the Pre-treatment Values.
Three visits (two pre-treatment and one baseline) were conducted prior to the receipt of investigational product (IP) and an average of the OCT measurements at these three visits was used as the pre-treatment value.

Secondary Outcome Measures

Change in Cystoid Macular Edema (CME) Based on Optical Coherence Tomography (OCT) Measurements in the Study Eye at 12 Months Compared to the Average of the Pre-treatment Values
Three visits (two pre-treatment and one baseline) were conducted prior to the receipt of investigational product (IP) and an average of the OCT measurements at these three visits was used as the pre-treatment value.
Changes in Amplitude of Photopic and Scotopic Responses on Electroretinogram (ERG) Testing at 6 Months as Compared to the Average of Pre-treatment Values
This outcome measure will not be reported.
Changes in Amplitude of Photopic and Scotopic Responses on Electroretinogram (ERG) Testing at 12 Months as Compared to the Average of Pre-treatment Values
This outcome measure will not be reported.
Change in Microperimetry at 6 Months as Compared to the Average of Pre-treatment Values
Three visits (two pre-treatment and one baseline) were conducted prior to the receipt of investigational product (IP) and an average of the microperimetry measurements at these three visits was used as the pre-treatment value.
Change in Microperimetry at 12 Months as Compared to the Average of Pre-treatment Values
Three visits (two pre-treatment and one baseline) were conducted prior to the receipt of investigational product (IP) and an average of the microperimetry measurements at these three visits was used as the pre-treatment value.
Change in Visual Field as Measured by HVF 30-2 Visual Field Testing at 6 Months as Compared to the Average of Pre-treatment Values
Three visits (two pre-treatment and one baseline) were conducted prior to the receipt of investigational product (IP) and an average of the HVF 30-2 measurements at these three visits was used as the pre-treatment value.
Change in Visual Field as Measured by HVF 30-2 Visual Field Testing at 12 Months as Compared to the Average of Pre-treatment Values
Three visits (two pre-treatment and one baseline) were conducted prior to the receipt of investigational product (IP) and an average of the HVF 30-2 measurements at these three visits was used as the pre-treatment value.
Number of Study Eyes Achieving a 15-letter or More Worsening in Electronic Visual Acuity (EVA) at 12 Months as Compared to Baseline
Visual Acuity was measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method.
Number of Ocular Adverse Events
Number of Non-ocular Adverse Events
Number of Severe Adverse Events

Full Information

First Posted
May 14, 2014
Last Updated
November 1, 2017
Sponsor
National Eye Institute (NEI)
Collaborators
The Emmes Company, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT02140164
Brief Title
Study of Oral Minocycline in Treating Bilateral Cystoid Macular Edema Associated With Retinitis Pigmentosa
Official Title
Pilot Study to Evaluate Oral Minocycline in the Treatment of Cystoid Macular Edema Associated With Retinitis Pigmentosa
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
May 2014 (undefined)
Primary Completion Date
November 2015 (Actual)
Study Completion Date
June 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Eye Institute (NEI)
Collaborators
The Emmes Company, LLC

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Background: - Some people with retinitis pigmentosa (RP) have macular edema (swelling) in the central retina. This can cause decreased central vision. The cause of macular edema is unknown, but may involve inflammation. The drug minocycline might help prevent inflammation and therefore might help treat macular edema and improve central visual function . Objectives: - To see if minocycline helps people with RP and macular edema. Eligibility: - People 12 years and older with RP who have macular edema in at least on eye. Design: Participants will be screened with medical and eye disease history. They will have an eye exam and blood tests. One eye with macular edema will be the study eye. If both eyes are affected, one will be designated the study eye. Participants will visit the clinic at least 9 times over at least 14 months. The first 3 study visits will be monthly, then every 2 months. Participants will start taking minocycline after visit 3. They will take 1 pill twice daily for at least 1 year. Participants will keep a medicine diary and bring it to each visit with their pill bottle and unused pills. At each study visit, participants will have some or all of the following tests: eye and thyroid exams blood and pregnancy tests microperimetry: participants will press a button when they see a light on a computer screen visual field measurement: participants will look at spots on a white screen to test side vision electroretinogram: A person will be dark adapted by sitting in the dark for 30 minutes. After the placement of numbing eye drops, special contact lenses will be placed . The participant will watch flashing lights and recordings will be made.
Detailed Description
Objective: Retinitis pigmentosa (RP) is a broad category of genetically heterogeneous diseases involving progressive visual loss by a constriction of visual field and loss of night vision. In up to one-third of patients, the peripheral vision loss can be compounded by central visual acuity loss from the development of cystic macular changes. While RP is a genetic disease, the etiology of progressive cell death, including that of associated cystoid macular edema (CME), is not completely understood. Inflammatory processes involving the activation of resident immune cells of the retina called microglia have been hypothesized to contribute. Minocycline inhibits the activation of microglia, decreasing the production of inflammatory factors implicated in RP progression. The objective of this study is to investigate the safety and possible efficacy of oral minocycline in participants with CME and RP. Study Population: Five participants, ages 12 and older, with unilateral or bilateral CME associated with RP will be enrolled initially. However, up to an additional five participants may be enrolled to replace participants who may withdraw from the study prior to reaching the Month 6 visit. Design: This is a pilot, single-center, uncontrolled, open-label, prospective, Phase 1/2 clinical trial to evaluate minocycline as a potential treatment for CME secondary to RP. A pre-treatment phase lasting two months will be instituted prior to investigational product (IP) initiation to assess the anatomical variability of CME as well as variability of other measurable parameters as part of the natural history of the disease. Participants will receive an oral dose of 100 mg (or appropriate weight adjusted pediatric dose) of minocycline twice daily for 12 months. There will be a common termination date, which will take place when the last recruited participant has received 12 months of IP. Participants who were recruited in the earlier part of the study will continue taking IP and be followed every two months until the common termination date. At each visit, participants will have visual acuity measured and will undergo optical coherence tomography (OCT) testing to measure retinal thickness. Measures of central visual field sensitivity full-field electroretinograms (ERG) and microperimetry (MP-1) will also be collected. Outcome Measures: The primary outcome is the change in CME based on OCT measurements in the study eye at 6 months compared to pre-treatment values. Secondary outcomes include changes in OCT thickness, changes in amplitude of photopic and scotopic responses on ERG testing, changes in microperimetry, and changes in visual field as measured by HVF 30-2 visual field testing at 6 months and 12 months compared to pre-treatment values, as well as CME changes on OCT at 12 months compared to pre-treatment values. Pre-treatment measurements will be analyzed to measure the natural variability of the CME as well as to measure the variability of the functional testing. Safety outcomes will include the number and severity of adverse events (AEs). Ocular safety outcomes will be indicated by changes in visual acuity, ocular surface changes, intraocular inflammation and any other ocular changes not consistent with the natural progression of RP.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Retinitis Pigmentosa
Keywords
Cystoid Macular Edema, Minocycline, Microglia, Retinitis Pigmentosa

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Minocycline
Arm Type
Experimental
Arm Description
Oral administration of minocycline
Intervention Type
Drug
Intervention Name(s)
Minocycline
Other Intervention Name(s)
Dynacin; serial number 73419626, Minocin; serial number 72309825, Minocin PAC, Myrac; serial number 76589055, Solodyn; serial number 78883462, Vectrin; serial number 78188505
Intervention Description
Oral dose of 100 mg (or appropriate weight-adjusted pediatric dose) of minocycline twice daily for 12 months.
Primary Outcome Measure Information:
Title
Change in Cystoid Macular Edema (CME) Based on Optical Coherence Tomography (OCT) Measurements in the Study Eye at 6 Months Compared to the Average of the Pre-treatment Values.
Description
Three visits (two pre-treatment and one baseline) were conducted prior to the receipt of investigational product (IP) and an average of the OCT measurements at these three visits was used as the pre-treatment value.
Time Frame
Pre-treatment and 6 Months
Secondary Outcome Measure Information:
Title
Change in Cystoid Macular Edema (CME) Based on Optical Coherence Tomography (OCT) Measurements in the Study Eye at 12 Months Compared to the Average of the Pre-treatment Values
Description
Three visits (two pre-treatment and one baseline) were conducted prior to the receipt of investigational product (IP) and an average of the OCT measurements at these three visits was used as the pre-treatment value.
Time Frame
Pre-treatment and 12 Months
Title
Changes in Amplitude of Photopic and Scotopic Responses on Electroretinogram (ERG) Testing at 6 Months as Compared to the Average of Pre-treatment Values
Description
This outcome measure will not be reported.
Time Frame
Pre-Treatment and 6 Months
Title
Changes in Amplitude of Photopic and Scotopic Responses on Electroretinogram (ERG) Testing at 12 Months as Compared to the Average of Pre-treatment Values
Description
This outcome measure will not be reported.
Time Frame
Pre-treatment and 12 Months
Title
Change in Microperimetry at 6 Months as Compared to the Average of Pre-treatment Values
Description
Three visits (two pre-treatment and one baseline) were conducted prior to the receipt of investigational product (IP) and an average of the microperimetry measurements at these three visits was used as the pre-treatment value.
Time Frame
Pre-treatment and 6 Months
Title
Change in Microperimetry at 12 Months as Compared to the Average of Pre-treatment Values
Description
Three visits (two pre-treatment and one baseline) were conducted prior to the receipt of investigational product (IP) and an average of the microperimetry measurements at these three visits was used as the pre-treatment value.
Time Frame
Pre-treatment and 12 Months
Title
Change in Visual Field as Measured by HVF 30-2 Visual Field Testing at 6 Months as Compared to the Average of Pre-treatment Values
Description
Three visits (two pre-treatment and one baseline) were conducted prior to the receipt of investigational product (IP) and an average of the HVF 30-2 measurements at these three visits was used as the pre-treatment value.
Time Frame
Pre-treatment and 6 Months
Title
Change in Visual Field as Measured by HVF 30-2 Visual Field Testing at 12 Months as Compared to the Average of Pre-treatment Values
Description
Three visits (two pre-treatment and one baseline) were conducted prior to the receipt of investigational product (IP) and an average of the HVF 30-2 measurements at these three visits was used as the pre-treatment value.
Time Frame
Pre-treatment and 12 Months
Title
Number of Study Eyes Achieving a 15-letter or More Worsening in Electronic Visual Acuity (EVA) at 12 Months as Compared to Baseline
Description
Visual Acuity was measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method.
Time Frame
Baseline and 12 Months
Title
Number of Ocular Adverse Events
Time Frame
Study Duration, up to 16 Months
Title
Number of Non-ocular Adverse Events
Time Frame
Study Duration, up to 16 Months
Title
Number of Severe Adverse Events
Time Frame
Study Duration, up to 16 Months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA: To be eligible, the following inclusion criteria must be met, where applicable. Participant must be 12 years of age or older. Participant (or legal guardian) must understand and sign the protocol's informed consent document. Participant must have evidence of retinitis pigmentosa (RP) as defined by characteristic electroretinogram (ERG) responses and visual fields. Participant must be able to swallow pills. Participant must have normal renal function and liver function or have mild abnormalities not above grade 1 as defined by the Common Terminology Criteria for Adverse Events v4.0 (CTCAE). Participant must agree to minimize exposure to sunlight or artificial ultraviolet (UV) rays and to wear protective clothing, sunglasses and sunscreen [minimum sun protection factor (SPF) 15] if s/he must be out in the sun. Any female participant of childbearing potential must have a negative pregnancy test at screening and be willing to undergo pregnancy tests throughout the study. Any female participant of childbearing potential and any male participant 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 at least one week after investigational product (IP) 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). EXCLUSION CRITERIA: A participant is not eligible if any of the following exclusion criteria are present. Participant is actively receiving study therapy in another investigational study. Participant is started on (or changed dosage of) topical or systemic carbonic anhydrase inhibitor (CAI) treatment in the 3 months prior to enrollment. Participant is actively receiving systemic steroids or has received systemic steroids in the 3 months prior to enrollment. Any female participant of childbearing potential that is pregnant, breast-feeding or planning to become pregnant during the study. Participant is expected to be unable to comply with study procedures or follow-up visits. Participant has evidence of an ocular disease other than RP in either eye that may confound the outcome of the study (e.g., diabetic retinopathy with 10 or more hemorrhages or microaneurysms, uveitis, pseudovitelliform macular degeneration, severe myopia). Participant is on ocular or systemic medications known to be toxic to the lens, retina or optic nerve (e.g., ethambutol, chloroquine, or hydroxychloroquine). Participant has a condition that would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control) by interfering with the participant s ability to engage in the required protocol evaluation and testing and/or comply with study visits. Participant has a history of chronic renal failure requiring dialysis or kidney transplant. Participant has a history of chronic hepatitis or liver failure. Participant has a history of thyroid cancer. Participant has an allergy or hypersensitivity to minocycline or any drug in the tetracycline family. Participant is currently taking a tetracycline medication. Participant is taking any medication that could adversely interact with minocycline such as methoxyflurane. Participant has a prior history of idiopathic intracranial hypertension.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Catherine A Cukras, M.D.
Organizational Affiliation
National Eye Institute (NEI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center, 9000 Rockville Pike
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
7386458
Citation
Boughman JA, Conneally PM, Nance WE. Population genetic studies of retinitis pigmentosa. Am J Hum Genet. 1980 Mar;32(2):223-35.
Results Reference
background
PubMed Identifier
7777280
Citation
Li ZY, Possin DE, Milam AH. Histopathology of bone spicule pigmentation in retinitis pigmentosa. Ophthalmology. 1995 May;102(5):805-16. doi: 10.1016/s0161-6420(95)30953-0.
Results Reference
background
PubMed Identifier
8398150
Citation
Chang GQ, Hao Y, Wong F. Apoptosis: final common pathway of photoreceptor death in rd, rds, and rhodopsin mutant mice. Neuron. 1993 Oct;11(4):595-605. doi: 10.1016/0896-6273(93)90072-y.
Results Reference
background
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2014-EI-0108.html
Description
NIH Clinical Center Detailed Web Page

Learn more about this trial

Study of Oral Minocycline in Treating Bilateral Cystoid Macular Edema Associated With Retinitis Pigmentosa

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