Conditions: Albinism Vision Loss
Keywords: Albinism Nitisinone Melanin Vision Loss
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 5
Healthy volunteers: no

Brief summary:
Background:

\- Oculocutaneous albinism, type 1B (OCA1B) is a genetic disease caused by problems in the gene that makes tyrosine. Tyrosine is an amino acid needed to produce pigment in the skin, hair, and eyes. People with OCA1B have pale skin, white hair, and light-colored eyes. Pigment in the back of the eye helps vision, so people with OCA-1B often have visual problems. Researchers want to see if a drug called nitisinone can help improve eye pigmentation and vision in people with OCA1B. Nitisinone is approved for treating a related genetic disease that causes problems with tyrosine, so it may help people with OCA1B.

Objectives:

\- To see if nitisinone can help improve eye pigmentation and vision in people with OCA1B.

Eligibility:

\- Individuals at least 18 years of age who have OCA1B.

Design:

* This study will last about 18 months. It requires eight outpatient visits, each about 3 months apart. Each visit will require 1 to 2 days of testing.
* Participants will be screened with a physical exam, eye exam, and medical history. They will have additional vision and neurological tests. They will be tested to see how their brain and retinas respond to light. They will also take hair and blood samples, and answer questions about diet.
* Participants will receive the study drug. They will take one pill a day for 1 year. They will keep track of the dose in a study diary.
* At the outpatient visits, participants will have the following tests:
* Medical history and physical exam
* Neurological and eye exams
* Retina function tests
* Tests of the skin and brain's response to light
* Blood and urine tests
* Dietary consultation
* Visual function questionnaire.
* After the end of the study, participants will return to the care of their regular eye doctor.

Detailed description:
Objective: The primary objective of this study is to evaluate oral nitisinone as a treatment that improves ocular pigmentation in adult participants with oculocutaneous albinism, type 1B (OCA1B). Secondary objectives of this study are to determine whether the selected outcome measures are robust enough to use in a larger trial and to assess whether oral nitisinone improves visual function, skin pigmentation, and hair pigmentation in participants with OCA1B.

Study Population: Five participants with OCA1B will be enrolled initially. However, up to an additional three participants may be enrolled to account for participants who withdraw from the study for any reason before the Month 12 visit.

Design: In this pilot, phase 1/2, single-site, prospective, open label trial, participants will receive 2 mg of oral nitisinone daily for at least one year, and they will be followed for at least 18 months. Ocular and non-ocular data will be collected at least every three months, with the first follow-up visit occurring three months after the final baseline visit. Participants will be required to have at least 8 outpatient visits at the NEI clinic over a period of 18 months. This study has a common termination date and therefore may continue for up to four years.

Outcome Measures: The primary outcome for the study is the absolute mean change in iris pigmentation on an 8-point scale at 12 months as compared to baseline. Participants left and right eyes will be analyzed. The absolute mean change in iris pigmentation for each eye on an 8-point scale at 3, 6 and 9 months compared to baseline will be assessed as secondary outcomes. Other secondary outcomes include the absolute and percent change in semi-quantitative iris pigmentation on image analysis; the absolute change in electronic visual acuity (EVA) for each eye and binocular vision; the absolute change in contrast sensitivity without glare, with medium glare, and with high glare for binocular vision; the absolute change in full-field ERG measures for each eye; and the absolute and percent change in melanin content in skin using skin reflectometry at 3, 6, 9 and 12 months as compared to baseline; Qualitative changes in hair, skin, and fundus pigmentation at 3, 6, 9 and 12 months as compared to previous visit will be assessed. The absolute and percent change in hair melanin will also be assessed at 12 months as compared to baseline. The number and severity of adverse events and the number of withdrawals will be assessed as safety outcomes.

Arms:
arm 1: Oral administration of nitisinone

Interventions: intervention 1: Nitisinone
Intervention descriptions: intervention 1: Oral dose of 2mg daily for 12 months.

Protocol document: