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Retinitis PigmentosaPhase 1/2NCT02140164

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

A Phase 1/2 study testing Minocycline in people with Retinitis Pigmentosa, run by National Eye Institute (NEI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Retinitis Pigmentosa
What is being tested?
Minocycline
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
1 siteUnited States
Study dates
May 2014to Jun 2016
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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).
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  • 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).

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Pilot Study to Evaluate Oral Minocycline in the Treatment of Cystoid Macular Edema Associated With Retinitis Pigmentosa

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 .
Read more

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.
Read the 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.

Being tested
Minocycline
Keywords
Cystoid Macular Edema, Minocycline, Microglia, Retinitis Pigmentosa
Medical subject headings
Retinitis Pigmentosa, Macular Edema, cyclopia sequence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MinocyclineDrug

    Also called Dynacin; serial number 73419626, Minocin; serial number 72309825, Minocin PAC, Myrac; serial number 76589055

    Oral dose of 100 mg (or appropriate weight-adjusted pediatric dose) of minocycline twice daily for 12 months.

Study groups in NCT02140164
Study groupRoleWhat they receive
MinocyclineExperimentalOral administration of minocycline
Receives: Drug: Minocycline

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Pre-treatment and 6 Months

Secondary outcomes (11)
  1. 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.

    Measured: Pre-treatment and 12 Months

  2. 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.

    Measured: Pre-Treatment and 6 Months

  3. 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.

    Measured: Pre-treatment and 12 Months

  4. 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.

    Measured: Pre-treatment and 6 Months

  5. 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.

    Measured: Pre-treatment and 12 Months

  6. 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.

    Measured: Pre-treatment and 6 Months

  7. 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.

    Measured: Pre-treatment and 12 Months

  8. 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.

    Measured: Baseline and 12 Months

  9. Number of Ocular Adverse Events

    Measured: Study Duration, up to 16 Months

  10. Number of Non-ocular Adverse Events

    Measured: Study Duration, up to 16 Months

  11. Number of Severe Adverse Events

    Measured: Study Duration, up to 16 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 May 2014 (estimated)
  2. Study startMay 2014
  3. Primary completionNov 2015
  4. Study completionJun 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02140164
Sponsor's protocol ID
140108
Other IDs
14-EI-0108
Status last verified
Nov 2017
First submitted
14 May 2014
Last updated
17 Apr 2024
Data monitoring committee
No
Individual data sharing
No

Publications

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

    PubMed 7386458
  • 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.

    PubMed 7777280
  • 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.

    PubMed 8398150
  • 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.

    PubMed 36882562

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Minocycline in people with Retinitis Pigmentosa, run by National Eye Institute (NEI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: Pre-treatment and 6 Months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02140164, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2024.

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