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

NCT02140164 | Completed Phase 1 Results

• 2 other identifiers: 14010814-EI-0108
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Retinitis Pigmentosa

Keywords

Cystoid Macular Edema; Minocycline; Microglia; Retinitis Pigmentosa

Outcome Measures

Primary Outcomes (1)

• 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.

  Pre-treatment and 6 Months

Secondary Outcomes (11)

• 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

  Pre-treatment and 12 Months

• Changes in Amplitude of Photopic and Scotopic Responses on Electroretinogram (ERG) Testing at 6 Months as Compared to the Average of Pre-treatment Values

  Pre-Treatment and 6 Months

• Changes in Amplitude of Photopic and Scotopic Responses on Electroretinogram (ERG) Testing at 12 Months as Compared to the Average of Pre-treatment Values

  Pre-treatment and 12 Months

• Change in Microperimetry at 6 Months as Compared to the Average of Pre-treatment Values

  Pre-treatment and 6 Months

• Change in Microperimetry at 12 Months as Compared to the Average of Pre-treatment Values

  Pre-treatment and 12 Months

Study Arms (1)

Minocycline

EXPERIMENTAL

Oral administration of minocycline

Drug: Minocycline

Interventions

Minocycline DRUG

Oral dose of 100 mg (or appropriate weight-adjusted pediatric dose) of minocycline twice daily for 12 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: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

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)

• Boughman JA, Conneally PM, Nance WE. Population genetic studies of retinitis pigmentosa. Am J Hum Genet. 1980 Mar;32(2):223-35.

  PMID: 7386458 BACKGROUND

• 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.

  PMID: 7777280 BACKGROUND

• 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.

  PMID: 8398150 BACKGROUND

• Dave AD, Chen KG, Chiang TT, Singaravelu J, Alvarez JA, Wong WT, Cukras CA. Oral minocycline for the treatment of retinitis pigmentosa-associated cystoid macular edema: results of a phase I/II clinical trial. Graefes Arch Clin Exp Ophthalmol. 2023 Aug;261(8):2209-2220. doi: 10.1007/s00417-023-05986-6. Epub 2023 Mar 8.

  PMID: 36882562 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Retinitis Pigmentosa; Macular Edema; cyclopia sequence

Interventions

Minocycline

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Dystrophies; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Macular Degeneration

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, M.D.

  National Eye Institute (NEI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2014
• First Posted: May 16, 2014
• Study Start: May 1, 2014
• Primary Completion: November 1, 2015
• Study Completion: June 1, 2016
• Last Updated: April 17, 2024
• Results First Posted: January 16, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)