Clinical trial NCT02140164
Conditions: Retinitis Pigmentosa
Keywords: Cystoid Macular Edema Minocycline Microglia Retinitis Pigmentosa
Sponsor: National Eye Institute (NEI)
Start date: 2014-05-01; Completion date: 2016-06-01
Enrollment: 7 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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.

Arms: arm 1: Oral administration of minocycline
Interventions: intervention 1: Minocycline
Intervention descriptions: intervention 1: Oral dose of 100 mg (or appropriate weight-adjusted pediatric dose) of minocycline twice daily for 12 months.

Protocol documents: