A Pilot Study of Nitisinone in the Treatment of Oculocutaneous Albinism, Type 1B
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Absolute Mean Change in Iris Pigmentation on an 8-point Iris Transillumination Scale at 12 Months as Compared to Baseline. Participants Left and Right Eyes Will be Analyzed.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Nitisinone
Oral administration of nitisinone
干预措施: Nitisinone (Drug)
结局指标
主要结局
Absolute Mean Change in Iris Pigmentation on an 8-point Iris Transillumination Scale at 12 Months as Compared to Baseline. Participants Left and Right Eyes Will be Analyzed.
时间窗: Baseline and 12 months
High-resolution (2544x1696) digital images of the anterior segment of both eyes were captured prior to pupil dilation using diffuse illumination and iris transillumination. An independent reviewer selected two transillumination images from each eye of each participant for each visit according to preset quality criteria. Images were coded, randomized and presented to a panel of 18 graders on a SHARP 90" HD LED TV. After instruction and a practice dataset, graders scored each image using an 8-point scale. Graders could score images with a single decimal place if they felt an image fell in between two of the standards. The iris transillumination scale ranged from 0 to 8, with lower scores reflective of greater iris pigmentation (melanin content). The mean across all graders and the two images for each participant's eye at baseline and 12 months was calculated; these mean grades were then used to calculate absolute change from baseline at 12 months.
次要结局
- Absolute Mean Change in Iris Pigmentation on an 8-point Iris Transillumination Scale at 6 Months as Compared to Baseline. Participants Left and Right Eyes Will be Analyzed.(Baseline and 6 months)
- Absolute Change in Semi-quantitative Iris Pigmentation for Each Eye at 3 Months as Compared to Baseline(Baseline and 3 months)
- Percent Change in Semi-quantitative Iris Pigmentation for Each Eye at 9 Months as Compared to Baseline(Baseline and 9 months)
- Percent Change in Semi-quantitative Iris Pigmentation for Each Eye at 12 Months as Compared to Baseline(Baseline and 12 months)
- Absolute Change in Electronic Visual Acuity at 12 Months Compared to Baseline(Baseline and 12 months)
- Absolute Change in Semi-quantitative Iris Pigmentation for Each Eye at 9 Months as Compared to Baseline(Baseline and 9 months)
- Percent Change in Semi-quantitative Iris Pigmentation for Each Eye at 3 Months as Compared to Baseline(Baseline and 3 months)
- Absolute Change in Electronic Visual Acuity at 6 Months Compared to Baseline(Baseline and 6 months)
- Absolute Change in Electronic Visual Acuity at 9 Months Compared to Baseline(Baseline and 9 months)
- Absolute Change in Contrast Sensitivity Without Glare at 3 Months Compared to Baseline(Baseline and 3 months)
- Absolute Change in Contrast Sensitivity Without Glare at 9 Months Compared to Baseline(Baseline and 9 months)
- Absolute Change in Contrast Sensitivity Without Glare at 12 Months Compared to Baseline(Baseline and 12 months)
- Absolute Mean Change in Iris Pigmentation on an 8-point Iris Transillumination Scale at 3 Months as Compared to Baseline. Participants Left and Right Eyes Will be Analyzed.(Baseline and 3 months)
- Absolute Mean Change in Iris Pigmentation on an 8-point Iris Transillumination Scale at 9 Months as Compared to Baseline. Participants Left and Right Eyes Will be Analyzed.(Baseline and 9 months)
- Absolute Change in Semi-quantitative Iris Pigmentation for Each Eye at 12 Months as Compared to Baseline(Baseline and 12 months)
- Absolute Change in Electronic Visual Acuity at 3 Months Compared to Baseline(Baseline and 3 months)
- Absolute Change in Semi-quantitative Iris Pigmentation for Each Eye at 6 Months as Compared to Baseline(Baseline and 6 months)
- Absolute Change in Contrast Sensitivity With Medium Glare at 6 Months Compared to Baseline(Baseline and 6 months)
- Percent Change in Semi-quantitative Iris Pigmentation for Each Eye at 6 Months as Compared to Baseline(Baseline and 6 months)
- Absolute Change in Contrast Sensitivity With High Glare at 9 Months Compared to Baseline(Baseline and 9 months)
- Absolute Change in Contrast Sensitivity With High Glare at 12 Months Compared to Baseline(Baseline and 12 months)
- Absolute Change in Contrast Sensitivity With High Glare at 6 Months Compared to Baseline(Baseline and 6 months)
- Absolute Change in Adjusted Melanin Index at 6 Months Compared to Baseline(Baseline and 6 Months)
- Absolute Change in Adjusted Melanin Index at 9 Months Compared to Baseline(Baseline and 9 Months)
- Absolute Change in Contrast Sensitivity Without Glare at 6 Months Compared to Baseline(Baseline and 6 months)
- Absolute Change in Contrast Sensitivity With Medium Glare at 12 Months Compared to Baseline(Baseline and 12 months)
- Absolute Change in Contrast Sensitivity With High Glare at 3 Months Compared to Baseline(Baseline and 3 months)
- Absolute Change in Contrast Sensitivity With Medium Glare at 3 Months Compared to Baseline(Baseline and 3 months)
- Absolute Change in Contrast Sensitivity With Medium Glare at 9 Months Compared to Baseline(Baseline and 9 months)
- Absolute Change in Adjusted Melanin Index at 3 Months Compared to Baseline(Baseline and 3 Months)
- Absolute Change in Electroretinogram (ERG) at Month 12 as Compared to Baseline.(Baseline and 12 months)
- Absolute Change in Adjusted Melanin Index at 12 Months Compared to Baseline(Baseline and 12 Months)
- Percent Change in Adjusted Melanin Index at 6 Months Compared to Baseline(Baseline and 6 Months)
- Percent Change in Adjusted Melanin Index at 9 Months Compared to Baseline(Baseline and 9 Months)
- Absolute Change in Melanin Index at 12 Months Compared to Baseline(Baseline and 12 Months)
- Absolute Change in Electroretinogram (ERG) at Month 6 as Compared to Baseline.(Baseline and 6 months)
- Qualitative Change in Skin Pigmentation at 3 Months Compared to Previous Visit.(Baseline and 3 months)
- Percent Change in Adjusted Melanin Index at 3 Months Compared to Baseline(Baseline and 3 Months)
- Percent Change in Adjusted Melanin Index at 12 Months Compared to Baseline(Baseline and 12 Months)
- Absolute Change in Melanin Index at 6 Months Compared to Baseline(Baseline and 6 Months)
- Qualitative Change in Skin Pigmentation at 6 Months Compared to Previous Visit.(3 Months and 6 months)
- Absolute Change in Melanin Index at 9 Months Compared to Baseline(Baseline and 9 Months)
- Percent Change in Melanin Index at 6 Months Compared to Baseline(Baseline and 6 Months)
- Qualitative Change in Fundus Pigmentation at 6 Months Compared to Previous Visit.(3 Months and 6 months)
- Absolute Change in Melanin Index at 3 Months Compared to Baseline(Baseline and 3 Months)
- Percent Change in Melanin Index at 3 Months Compared to Baseline(Baseline and 3 Months)
- Percent Change in Melanin Index at 9 Months Compared to Baseline(Baseline and 9 Months)
- Qualitative Change in Hair Pigmentation at 3 Months Compared to Previous Visit.(Baseline and 3 months)
- Qualitative Change in Hair Pigmentation at 6 Months Compared to Previous Visit.(3 Months and 6 months)
- Qualitative Change in Hair Pigmentation at 9 Months Compared to Previous Visit.(6 Months and 9 months)
- Qualitative Change in Fundus Pigmentation at 9 Months Compared to Previous Visit.(6 Months and 9 months)
- Percent Change in Melanin Index at 12 Months Compared to Baseline(Baseline and 12 Months)
- Qualitative Change in Hair Pigmentation at 12 Months Compared to Previous Visit.(9 Months and 12 months)
- Qualitative Change in Skin Pigmentation at 9 Months Compared to Previous Visit.(6 Months and 9 months)
- Qualitative Change in Skin Pigmentation at 12 Months Compared to Previous Visit.(9 Months and 12 months)
- Qualitative Change in Fundus Pigmentation at 3 Months Compared to Previous Visit.(Baseline and 3 months)
- Qualitative Change in Fundus Pigmentation at 12 Months Compared to Previous Visit.(9 Months and 12 months)
- Absolute Change in Hair Melanin at 12 Months Compared to Baseline(Baseline and 12 months)
- Percent Change in Hair Melanin at 12 Months Compared to Baseline(Baseline and 12 months)