9-cis Beta-Carotene-Rich Extract of Dunaliella Alga in Retinitis Pigmentosa Patients

Treatment With 9-cis Beta-Carotene-Rich Extract of Dunaliella Alga in Retinitis Pigmentosa Patients - a Randomized Crossover Double Masked Study

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Retinitis Pigmentosa
• Intervention / Treatment: Dietary supplement: 9-cis beta-Carotene-rich extract of Dunaliella alga; Other: Placebo Corn Oil

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 41
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Lori Gueta; Phone Number: 972-3-5308132; Email: Lori.Gueta@sheba.health.gov.il

Study Locations

• Israel
  • Tel Litwinsky, Israel, 52621
    • Goldschleger Eye Institute, Sheba Medical Center,
    • Contact: Lori Gueta; Phone Number: 972-3-5308132; Email: Lori.Gueta@sheba.health.gov.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Written informed consent to participate in the study
2. Men or women aged 18 years or older
3. Electroretinogram (ERG) responses compatible with the diagnosis of retinitis pigmentosa
4. Positive for mutation(s) in retinoid cycle related genes

Exclusion Criteria:

1. Currently a smoker
2. Current use of vitamin A/ β-carotene supplements
3. Known mutations in the ABCA4 gene
4. 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
5. History of malignancy, excepting basal or squamous cell skin carcinoma
6. Women who are pregnant, or breast feeding, or are premenopausal but not using chemical or mechanical contraception
7. 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
8. History of alcohol abuse or drug abuse or both
9. Intention to engage in vigorous exercise or an aggressive diet regimen
10. Uncontrolled endocrine or metabolic disease
11. Participation in another investigational drug study within 4 weeks prior to enrolment
12. 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
13. Initiation of hormone replacement therapy or oral contraceptive therapy within 3 months prior to enrolment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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)	Dietary supplement: 9-cis beta-Carotene-rich extract of Dunaliella alga; Participants will be instructed to take two soft-gel capsules twice daily (total of 4 capsules per day) for a period of 90 days. Each soft-gel capsule contains oil extraction of the alga Dunaliella, which is rich in beta-carotene (composed of approximately 70% 9-cis and 30% all-trans isomers). The capsules are manufactured by Hetchyn Ingredients Biotechnology Co., Ltd.; Other Names: Dunaliella alga
Placebo Comparator: 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.	Other: Placebo Corn Oil; Participants will be instructed to take two soft-gel capsules twice daily (total of 4 capsules per day) for a period of 90 days. The placebo capsules contain corn oil and are manufactured to be identical in appearance (size, color, and texture) to the active Dunaliella soft-gels to maintain masking.; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Retinal Sensitivity via Microperimetry	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.	Baseline (Month 0), End of first treatment (Month 3), End of washout (Month 9), and End of second treatment (Month 12).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Full-Field Electroretinogram (ERG)	Measurement of the electrical response of the retina (b-wave amplitude in microvolts) to light stimuli under scotopic (dark-adapted) and photopic (light-adapted) conditions.	Months 0, 3, 9, and 12
Change in Best-Corrected Visual Acuity (BCVA)	Measurement of visual sharpness using the ETDRS letter chart at a standard distance.	Months 0, 3, 9, and 12
Change in Full Field Scotopic Threshold (FST)	Measurement of the lowest light intensity perceived by the patient across the entire visual field, measured in decibels (dB).	Months 0, 3, 9, 12
Change in Plasma beta-carotene Levels	Laboratory analysis of blood samples to measure the concentration of $\beta$-carotene (mg/L) to correlate with clinical response and ensure washout efficiency.	Months 0, 3, 9, and 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Pupil Response (Chromatic Pupilloperimetry)	Measurement of pupil constriction in response to focal chromatic light stimuli (red and blue light) to assess rod and cone function.	Months 0, 3, 9, 12
Change in Retinal Layer Thickness by SD-OCT	Use of Spectral Domain Optical Coherence Tomography (SD-OCT) imaging to monitor changes in the thickness of retinal layers (in micrometers)	Months 0, 3, 9, 12
Change in Ellipsoid Zone (EZ) Area (mm^2) as Measured by SD-OCT En Face Imaging	The Ellipsoid Zone (EZ) area reflects photoreceptor integrity. The total area of preserved EZ will be quantified in square millimeters (mm^2) using semi-automated segmentation of SD-OCT volume scans. The outcome reported is the mean change in EZ area from baseline to each follow-up time point. A decrease in area represents disease progression.	Baseline (Month 0), End of first treatment (Month 3), End of washout (Month 9), and End of second treatment (Month 12).
Change from in Ellipsoid Zone (EZ) Length as Measured by SD-OCT	The Ellipsoid Zone (EZ) length (also known as the EZ width or trans-foveal EZ diameter) represents the horizontal extent of preserved photoreceptor integrity. This measure is quantified in micrometers (µm) or millimeters (mm) using a standardized horizontal B-scan passing through the fovea (Spectral-Domain Optical Coherence Tomography - SD-OCT). A decrease in EZ length reflects the progressive constriction of the visual field typical of Retinitis Pigmentosa. The analysis will compare the rate of change during treatment periods versus the baseline measurement and washout period.	Baseline (Month 0), End of first treatment (Month 3), End of washout (Month 9), and End of second treatment (Month 12).
Change in Contrast Sensitivity	Assessment of the patient's ability to distinguish foreground objects from backgrounds of similar luminance	Months 0, 3, 9, 12
Dark Adaptation Rate	Measurement of the time required for the retina to recover sensitivity in the dark following a bright light bleach.	Months 0, 3, 9, 12
Plasma Levels of Retinol and RBP4	Measurement of plasma concentrations of Vitamin A (retinol) and Retinol Binding Protein 4 (RBP4) in mg/L	Months 0, 3, 9, 12
Change from Baseline in Intraocular Pressure (IOP) Measured by Goldmann Applanation Tonometry (mmHg).	IOP is measured in millimeters of mercury (mmHg) using Goldmann Applanation Tonometry. The outcome reported is the mean change in IOP from baseline to assess the physiological effect and safety of the treatment.	Months 0, 3, 9, 12
Number of Participants With Clinically Significant Abnormal Findings on Slit Lamp Biomicroscopy.	Slit lamp examination includes evaluation of the eyelids, conjunctiva, cornea, iris, and lens. Anterior chamber cells and flare will be graded according to the Standardization of Uveitis Nomenclature (SUN) criteria (scale 0-4+). A "clinically significant abnormal finding" is defined as any new finding or worsening of an existing condition (e.g., increase in SUN grade or LOCS III cataract score) that the investigator judges to be clinically relevant	Baseline (Month 0), Month 3 (End of first treatment), Month 9 (End of washout), and Month 12 (End of second treatment)
Change in Quality of Life (Q25 Questionnaire)	Total score from the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) to assess the impact of vision on daily activities. Scores range from 0 to 100, where higher scores indicate better health-related quality of life.	Months 0, 3, 9, 12

Collaborators and Investigators

• Sponsor: Sheba Medical Center

Publications and helpful links

General Publications

• Rotenstreich Y, Belkin M, Sadetzki S, Chetrit A, Ferman-Attar G, Sher I, Harari A, Shaish A, Harats D. Treatment with 9-cis beta-carotene-rich powder in patients with retinitis pigmentosa: a randomized crossover trial. JAMA Ophthalmol. 2013 Aug;131(8):985-92. doi: 10.1001/jamaophthalmol.2013.147.
• Rotenstreich Y, Harats D, Shaish A, Pras E, Belkin M. Treatment of a retinal dystrophy, fundus albipunctatus, with oral 9-cis-beta-carotene. Br J Ophthalmol. 2010 May;94(5):616-21. doi: 10.1136/bjo.2009.167049. Epub 2009 Dec 2.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2029

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: March 28, 2026
• First Posted (Actual): April 3, 2026

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: March 28, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: retinitis pigmentosa; beta carotene; retinoid cycle
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Eye Diseases; Eye Diseases, Hereditary; Retinal Diseases; Retinal Dystrophies; Retinal Degeneration; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Retinitis Pigmentosa
• Other Study ID Numbers: 6191-19-SMC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The investigators have not yet determined if individual participant data will be shared. This decision will depend on the availability of a secure platform for data hosting and ensuring strict adherence to patient privacy regulations and informed consent agreements regarding genetic data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No