Retinitis PigmentosaPhase 1/2NCT07509229
9-cis Beta-Carotene-Rich Extract of Dunaliella Alga in Retinitis Pigmentosa Patients
A Phase 1/2 study testing 9-cis beta-Carotene-rich extract of Dunaliella alga in people with Retinitis Pigmentosa, run by Sheba Medical Center at 1 site in Israel.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Retinitis Pigmentosa
- What is being tested?
- 9-cis beta-Carotene-rich extract of Dunaliella alga
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 41 participants
- Where
- 1 siteIsrael
- Study dates
- 26 Jul 2026to 30 Apr 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Israel1 site
Goldschleger Eye Institute, Sheba Medical Center,
Tel HaShomer, 52621
About this study
Official title: 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.
Read the 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.
- Conditions
- Retinitis Pigmentosa
- Being tested
- 9-cis beta-Carotene-rich extract of Dunaliella alga, Placebo Corn Oil
- Keywords
- retinitis pigmentosa, retinoid cycle, beta carotene
- Medical subject headings
- Retinitis Pigmentosa
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
9-cis beta-Carotene-rich extract of Dunaliella algaDietary supplement
Also called 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.
Placebo Corn OilOther
Also called Placebo
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.
| Study group | Role | What they receive |
|---|---|---|
| 9-cis beta-carotene rich Dunaliella algae. | Experimental | 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) Receives: Dietary Supplement: 9-cis beta-Carotene-rich extract of Dunaliella alga |
| Corn Oil | Placebo comparator | 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. Receives: Other: Placebo Corn Oil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline (Month 0), End of first treatment (Month 3), End of washout (Month 9), and End of second treatment (Month 12).
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: Months 0, 3, 9, and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2026
- Study start26 Jul 2026 (estimated)
- Primary completion30 Apr 2028 (estimated)
- Study completion30 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Retinitis PigmentosaStudies of the same condition, open and under way.
- More trials run by Sheba Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Randomised
- Intervention model
- Crossover
- Model description
- This is a double-masked, randomized, 2-period crossover study. Participants are assigned to one of two arms: Arm A: Active supplement (9-cisbeta-carotene) for 3 months, followed by a 6-month washout period, then Placebo (corn oil) for 3 months. Arm B: Placebo for 3 months, followed by a 6-month washout period, then Active supplement for 3 months.The 6-month washout period is strategically included to ensure plasma beta-carotene levels return to baseline before the second treatment period begins, preventing "carry-over" effects from the supplement.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 41 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Dr. Ygal Rotenstreich, Sheba Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07509229
- Sponsor's protocol ID
- 6191-19-SMC
- Status last verified
- Jul 2026
- First submitted
- 11 Mar 2026
- Last updated
- 27 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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.
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.
PubMed 23700011Rotenstreich 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.
PubMed 19955196
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment With 9-cis Beta-Carotene-Rich Extract of Dunaliella Alga in Retinitis Pigmentosa Patients - a Randomized Crossover Double Masked Study
- ClinicalTrials.gov ID
- NCT07509229
- Acronym / sponsor ID
- 6191-19-SMC
- Conditions
- Retinitis Pigmentosa
- Keywords
- retinitis pigmentosa, retinoid cycle, beta carotene
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 41 participants (estimated)
- Lead sponsor
- Sheba Medical CenterOther government
- Study start
- 26 Jul 2026 (estimated)
- Primary completion
- 30 Apr 2028 (estimated)
- Study completion
- 30 Apr 2029 (estimated)
- First posted
- 3 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a double-masked, randomized, 2-period crossover study. Participants are assigned to one of two arms: Arm A: Active supplement (9-cisbeta-carotene) for 3 months, followed by a 6-month washout period, then Placebo (corn oil) for 3 months. Arm B: Placebo for 3 months, followed by a 6-month washout period, then Active supplement for 3 months.The 6-month washout period is strategically included to ensure plasma beta-carotene levels return to baseline before the second treatment period begins, preventing "carry-over" effects from the supplement.
| Arm | Type | Receives |
|---|---|---|
| 9-cis beta-carotene rich Dunaliella algae. | Experimental | Dietary Supplement: 9-cis beta-Carotene-rich extract of Dunaliella algaParticipants 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) |
| Corn Oil | Placebo comparator | Other: Placebo Corn OilParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 9-cis beta-Carotene-rich extract of Dunaliella algaAlso: Dunaliella algaParticipants 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. | Dietary supplement | 9-cis beta-carotene rich Dunaliella algae. |
| Placebo Corn OilAlso: PlaceboParticipants 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 | Corn Oil |
Primary outcome
Change in Retinal Sensitivity via Microperimetry
Time frame: 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.
4 secondary outcomes
Change in Full-Field Electroretinogram (ERG)
Time frame: Months 0, 3, 9, and 12
Change in Best-Corrected Visual Acuity (BCVA)
Time frame: Months 0, 3, 9, and 12
Change in Full Field Scotopic Threshold (FST)
Time frame: Months 0, 3, 9, 12
Change in Plasma beta-carotene Levels
Time frame: Months 0, 3, 9, and 12
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2026.
- Background: PubMed 23700011Rotenstreich 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.
- Background: PubMed 19955196Rotenstreich 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.
- Individual participant dataSharing planned: Undecided. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 9-cis beta-Carotene-rich extract of Dunaliella alga in people with Retinitis Pigmentosa, run by Sheba Medical Center at 1 site in Israel.
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 4 inclusion and 13 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: enrolling by invitation, as of the sponsor's last update on 27 Jul 2026. 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 Israel. 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. Some participants in this study may receive a placebo. 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?
This study is still under way. Results are not available in the source record yet.
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 Retinal Sensitivity via Microperimetry (time frame: Baseline (Month 0), End of first treatment (Month 3), End of washout (Month 9), and End of second treatment (Month 12).). 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 NCT07509229, which also lists 2 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 27 Jul 2026.