Treatment With 9-cis Beta-Carotene-Rich Extract of Dunaliella Alga in Retinitis Pigmentosa Patients - a Randomized Crossover Double Masked Study
试验速览
- 阶段
- 1 期
- 状态
- Enrolling By Invitation
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Change in Retinal Sensitivity via Microperimetry
研究概览
简要总结
The goal of this clinical trial is to learn if a natural supplement called 9-cis beta-carotene (derived from the Dunaliella alga) can improve vision and retinal function in adults with Retinitis Pigmentosa. The study will also monitor the safety of the food supplement and how it affects levels of Vitamin A-related proteins in the blood. The main questions the study aims to answer are: (1) Does taking the supplement improve light sensitivity in the retina (measured by microperimetry)? (2) Does the supplement improve electrical responses in the eye (ERG) or other visual functions like contrast and color vision? (3) How do blood levels of beta-carotene and Vitamin A change during treatment? Researchers will use a crossover design. This means every participant will receive both the active supplement and a placebo (a "dummy" pill with corn oil) at different times during the study to compare the results. Participants will take two soft-gel capsules twice a day for 3 months, undergo a 6-month "washout" period where no study capsules are taken.Then they will take the opposite capsules (either the supplement or the placebo) for another 3 months. The participants will visit the clinic 4 times over the course of 12 months for eye exams, eye imaging (like OCT), and blood tests. Participants will also receive follow-up phone calls every 6 weeks to check on their progress and health.
详细描述
This study is a randomized, double-masked, crossover, placebo-controlled clinical trial designed to evaluate the efficacy of a 9-cis beta-carotene-rich alga (Dunaliella) supplement in patients with Retinitis Pigmentosa (RP). The study specifically targets individuals with mutations in genes related to the retinoid cycle, a critical process for maintaining vision. Previous research has shown that prolonged treatment (at least 3 months) with 9-cis beta-carotene can lead to significant improvements in retinal function and substential visual field cahnges in a subset of RP patients. Because beta-carotene persists in the body, this study utilizes an extended 6-month washout period between treatment arms to ensure plasma levels return to baseline, allowing for a clear comparison between the active supplement and the placebo.
Participants will be randomized into three blocks based on their baseline electroretinogram (ERG) b-wave responses (low, medium, or high) to ensure balanced groups. As a crossover study, every participant will complete two 3-month treatment periods: one with the active Dunaliella soft-gels and one with a corn oil placebo. The total study duration is 12 months, divided into the following phases: Initial Treatment (Months 0-3): Participants take 2 capsules twice daily of either Dunaliella oil (containing 20 mg of beta-carotene) or a placebo. Washout Period (Months 3-9): A 6-month period with no study medication to allow the supplement to clear from the system. Crossed Treatment (Months 9-12): Participants switch to the opposite treatment for a final 3 months. Participants will visit the clinic at the beginning and end of each treatment phase (Months 0, 3, 9, and 12). At these visits, the following assessments will be performed: Primary Objective: Measuring changes in retinal sensitivity via microperimetry. Secondary Objectives: Evaluating electrical retinal activity (ERG), visual acuity (ETDRS), contrast sensitivity, and retinal structure using Optical Coherence Tomography (OCT) and fundus photography. Blood samples will be analyzed for plasma levels of beta-carotene, retinol, and Retinal Binding Protein 4 (RBP4). Participants will complete the NEI VFQ-25 life quality questionnaire to assess the functional impact of the treatment. Adherence will be monitored through capsule counts at each visit, and safety will be assessed via medical history reviews and phone calls every 6 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The study uses a double-masked design to prevent bias. The active supplement (Dunaliella oil) and the placebo (corn oil) are provided in soft-gel capsules that are identical in size, shape, color, and packaging.
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
- •Written informed consent to participate in the study
- •Men or women aged 18 years or older
- •Electroretinogram (ERG) responses compatible with the diagnosis of retinitis pigmentosa
- •Positive for mutation(s) in retinoid cycle related genes
排除标准
- •Currently a smoker
- •Current use of vitamin A/ β-carotene supplements
- •Known mutations in the ABCA4 gene
- •Active arterial disease within 3 months prior to enrolment in the study, e.g. unstable angina, myocardial infarction, transient ischemic attack, stroke, coronary artery bypass graft surgery
- •History of malignancy, excepting basal or squamous cell skin carcinoma
- •Women who are pregnant, or breast feeding, or are premenopausal but not using chemical or mechanical contraception
- •Uncontrolled hypertension, defined either as resting diastolic blood pressure >95 mmHg (taken from the mean of 3 readings) or as resting systolic blood pressure >180 mmHg
- •History of alcohol abuse or drug abuse or both
- •Intention to engage in vigorous exercise or an aggressive diet regimen
- •Uncontrolled endocrine or metabolic disease
- •Participation in another investigational drug study within 4 weeks prior to enrolment
- •Serious or unstable medical or psychological condition which, in the opinion of the PI, would compromise the subject's safety or successful participation in the study
- •Initiation of hormone replacement therapy or oral contraceptive therapy within 3 months prior to enrolment
研究组 & 干预措施
Corn Oil
Participants receive two soft-gel capsules twice daily (total 4 capsules/day). Each capsule contains corn oil, manufactured to match the appearance of the active supplement.
干预措施: Placebo Corn Oil (Other)
9-cis beta-carotene rich Dunaliella algae.
Participants receive two soft-gel capsules twice daily (total 4 capsules/day). Each capsule contains Dunaliella algae, rich in beta-carotene (70% 9-cis and 30% all-trans isomers)
干预措施: 9-cis beta-Carotene-rich extract of Dunaliella alga (Dietary Supplement)
结局指标
主要结局
Change in Retinal Sensitivity via Microperimetry
时间窗: Baseline (Month 0), End of first treatment (Month 3), End of washout (Month 9), and End of second treatment (Month 12).
Microperimetry will be used to measure the mean retinal sensitivity (expressed in decibels, dB) in the central visual field. This test assesses the minimum light intensity a patient can perceive at specific points on the retina. An increase in dB indicates improved retinal function and light sensitivity.
次要结局
- Change in Full-Field Electroretinogram (ERG)(Months 0, 3, 9, and 12)
- Change in Best-Corrected Visual Acuity (BCVA)(Months 0, 3, 9, and 12)
- Change in Full Field Scotopic Threshold (FST)(Months 0, 3, 9, 12)
- Change in Plasma beta-carotene Levels(Months 0, 3, 9, and 12)
研究者
Dr. Ygal Rotenstreich
Head, Electrophysiology Clinic Goldschleger Eye Institute Sheba Medical Center
Sheba Medical Center