<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01680510</url>
  </required_header>
  <id_info>
    <org_study_id>SHEBA-12-9373-YR-CTIL</org_study_id>
    <nct_id>NCT01680510</nct_id>
  </id_info>
  <brief_title>The Effect of Oral Administration of 9-cis β Carotene Rich Powder of the Alga Dunaliella Bardawil</brief_title>
  <official_title>The Effect of Oral Administration of 9-cis β Carotene Rich Powder of the Alga Dunaliella Bardawil on Visual Functions in Patients With Retinitis Pigmentosa</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sheba Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sheba Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Retinitis pigmentosa is a genetically disease consisting of progressive retinal degeneration&#xD;
      starting in the rods. Its prevalence is 1:4000 people and is the fourth most common blinding&#xD;
      disease in Israel in 2004 [7% of all blindness]. The investigators treated a non-progressive&#xD;
      form of the disease [Fundus Albipunctatus] by oral therapy of the food supplement made from&#xD;
      alga Dunaliella Bardawil composed of approximately 50% 9-cis β-carotene. The alga Dunaliella&#xD;
      Bardawil accumulates high concentration of β -carotene when grown under appropriate&#xD;
      conditions. The β -carotene of the alga is composed of approximately 50% of all-trans - β&#xD;
      carotene and 50% 9-cis β -carotene.&#xD;
&#xD;
      The 9-cis β -carotene has been shown to be a precursor of 9-cis retinoic acid both in-vitro&#xD;
      in human intestinal mucosa and in-vivo in a ferret, perfused with 9-cis b-carotene. The night&#xD;
      vision, as measured objectively by electroretinography (ERG) more than doubled in six&#xD;
      patients tested following treatment. The visual field was also improved significantly. In a&#xD;
      more recent study the investigators treated 29 retinitis pigmentosa patients with the 9-cis b&#xD;
      Carotene algae Dunaliella Bardawil in a double masked placebo control cross over trial.&#xD;
      Significant improvement in retinal function was recorded in 34% of the patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 2012</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Alga vs. placebo</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean binocular maximal scotopic electroretinogram b-wave response</measure>
    <time_frame>At weeks 0, 24,48,72</time_frame>
    <description>Using the protocol of the International Society for Clinical Electrophysiology of Vision and the UTAS 3000 system (LKC Technologies, Gaithersburg, MD), full-field electroretinographic responses will be recorded from both eyes of each patient. For scotopic conditions, maximal ERG b-wave responses will be recorded following 30 minutes of dark adaptation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The area within the Dark adapted chromatic Goldamann Visual field in isopters in cm2</measure>
    <time_frame>at weeks 0, 24, 48, 72</time_frame>
    <description>Kinetic visual field for chromatic stimuli will be recorded in both eyes after 30 minutes of dark adaptation. Area of vision within the isopter will be measured by software in cm2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The area within Goldamann Visual field in isopters in cm2</measure>
    <time_frame>at weeks 0, 24, 48, 72</time_frame>
    <description>Kinetic visual field will be recorded in both eyes. Area of vision within the isopter will be measured by software in cm2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean binocular maximal photopic electroretinogram b-wave response</measure>
    <time_frame>Weeks 0, 24, 48, 72</time_frame>
    <description>Using the protocol of the International Society for Clinical Electrophysiology of Vision and the UTAS 3000 system (LKC Technologies, Gaithersburg, MD), full-field photopic electroretinographic responses will be recorded from both eyes of each patient.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best-corrected visual acuity (EDTRS)</measure>
    <time_frame>Weeks 0, 24, 48, 72</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Objective visual field by chromatic multifocal pupillometer</measure>
    <time_frame>Weeks 0, 24,48,72</time_frame>
    <description>Objective evaluation of 76 point visual field using a chromatic multifocal pupillometer.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Retinitis Pigmentosa</condition>
  <arm_group>
    <arm_group_label>Alga Dunaliella Bardawil 9-cis beta Carotene Rich Powder</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>50 patients will receive first the capsules containing the alga Dunaliella Bardawil 9-cis beta-Carotene rich powder and after 24 weeks of washout period will receive capsule containing placebo (Starch).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo (Starch)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The other 50 Patients will receive first the placebo (Starch) capsules and after 24 weeks of washout period will receive capsules containing the alga Dunaliella Bardawil 9-cis beta-Carotene rich powder .</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Alga Dunaliella Bardawil</intervention_name>
    <arm_group_label>Alga Dunaliella Bardawil 9-cis beta Carotene Rich Powder</arm_group_label>
    <arm_group_label>Placebo (Starch)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo (starch)</intervention_name>
    <arm_group_label>Alga Dunaliella Bardawil 9-cis beta Carotene Rich Powder</arm_group_label>
    <arm_group_label>Placebo (Starch)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent to participate in the study.&#xD;
&#xD;
          -  Men or women aged 18 years or older.&#xD;
&#xD;
          -  Electroretinogram (ERG) responses compatible with the diagnosis of Retinitis&#xD;
             Pigmentosa&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current smokers.&#xD;
&#xD;
          -  Current use of Vitamin A/ beta carotene supplements.&#xD;
&#xD;
          -  Active arterial disease within 3 months of study entry such as unstable angina,&#xD;
             myocardial infarction, transient ischemic attack (TIA), stroke, and coronary artery&#xD;
             bypass graft (CABG) surgery.&#xD;
&#xD;
          -  History of malignancy, except basal or squamous cell skin carcinoma.&#xD;
&#xD;
          -  Pregnant women, women who are breast feeding, and women of childbearing potential who&#xD;
             are not using chemical or mechanical contraception.&#xD;
&#xD;
          -  Uncontrolled hypertension defined as either resting diastolic blood pressure of&#xD;
             &gt;95mmHg (taken from the mean of 3 readings) or resting systolic blood Pressure of &gt;&#xD;
             180 mmHg.&#xD;
&#xD;
          -  History of alcohol abuse or drug abuse, or both.&#xD;
&#xD;
          -  Patient plans to engage in vigorous exercise or an aggressive diet regimen.&#xD;
&#xD;
          -  Uncontrolled endocrine or metabolic disease.&#xD;
&#xD;
          -  Participation in another investigational drug study within 4 weeks of entry into this&#xD;
             study.&#xD;
&#xD;
          -  Serious or unstable medical or psychological condition that, in the opinion of the&#xD;
             investigator, would compromise the subject's safety or successful participation in the&#xD;
             study.&#xD;
&#xD;
          -  Subject whose hormone replacement therapy (HRT) or oral contraceptive therapy (OCT)&#xD;
             was initiated within the 3 month prior to enrollment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ygal Rotenstreich, Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sheba Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sheba Medical Center</name>
      <address>
        <city>Tel Hashomer</city>
        <zip>52621</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <reference>
    <citation>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.</citation>
    <PMID>23700011</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>19955196</PMID>
  </reference>
  <reference>
    <citation>Skaat A, Sher I, Kolker A, Elyasiv S, Rosenfeld E, Mhajna M, Melamed S, Belkin M, Rotenstreich Y. Pupillometer-based objective chromatic perimetry in normal eyes and patients with retinal photoreceptor dystrophies. Invest Ophthalmol Vis Sci. 2013 Apr 17;54(4):2761-70. doi: 10.1167/iovs.12-11127.</citation>
    <PMID>23482470</PMID>
  </reference>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>September 4, 2012</study_first_submitted>
  <study_first_submitted_qc>September 4, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 7, 2012</study_first_posted>
  <last_update_submitted>January 15, 2023</last_update_submitted>
  <last_update_submitted_qc>January 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sheba Medical Center</investigator_affiliation>
    <investigator_full_name>Dr. Ygal Rotenstreich</investigator_full_name>
    <investigator_title>Director of Hereditary Retinal Diseases and Electrophysiology Clinic</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Retinitis</mesh_term>
    <mesh_term>Retinitis Pigmentosa</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01680510
org study id: SHEBA-12-9373-YR-CTIL
nct id: NCT01680510
lead sponsor: 
has dmc: Yes
Retinitis pigmentosa is a genetically disease consisting of progressive retinal degeneration
      starting in the rods. Its prevalence is 1:4000 people and is the fourth most common blinding
      disease in Israel in 2004 [7% of all blindness]. The investigators treated a non-progressive
      form of the disease [Fundus Albipunctatus] by oral therapy of the food supplement made from
      alga Dunaliella Bardawil composed of approximately 50% 9-cis β-carotene. The alga Dunaliella
      Bardawil accumulates high concentration of β -carotene when grown under appropriate
      conditions. The β -carotene of the alga is composed of approximately 50% of all-trans - β
      carotene and 50% 9-cis β -carotene.

      The 9-cis β -carotene has been shown to be a precursor of 9-cis retinoic acid both in-vitro
      in human intestinal mucosa and in-vivo in a ferret, perfused with 9-cis b-carotene. The night
      vision, as measured objectively by electroretinography (ERG) more than doubled in six
      patients tested following treatment. The visual field was also improved significantly. In a
      more recent study the investigators treated 29 retinitis pigmentosa patients with the 9-cis b
      Carotene algae Dunaliella Bardawil in a double masked placebo control cross over trial.
      Significant improvement in retinal function was recorded in 34% of the patients.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Alga vs. placebo
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Mean binocular maximal scotopic electroretinogram b-wave response
time frame: At weeks 0, 24,48,72
description: Using the protocol of the International Society for Clinical Electrophysiology of Vision and the UTAS 3000 system (LKC Technologies, Gaithersburg, MD), full-field electroretinographic responses will be recorded from both eyes of each patient. For scotopic conditions, maximal ERG b-wave responses will be recorded following 30 minutes of dark adaptation.
measure: The area within the Dark adapted chromatic Goldamann Visual field in isopters in cm2
time frame: at weeks 0, 24, 48, 72
description: Kinetic visual field for chromatic stimuli will be recorded in both eyes after 30 minutes of dark adaptation. Area of vision within the isopter will be measured by software in cm2.
measure: The area within Goldamann Visual field in isopters in cm2
time frame: at weeks 0, 24, 48, 72
description: Kinetic visual field will be recorded in both eyes. Area of vision within the isopter will be measured by software in cm2.
measure: Mean binocular maximal photopic electroretinogram b-wave response
time frame: Weeks 0, 24, 48, 72
description: Using the protocol of the International Society for Clinical Electrophysiology of Vision and the UTAS 3000 system (LKC Technologies, Gaithersburg, MD), full-field photopic electroretinographic responses will be recorded from both eyes of each patient.
measure: Best-corrected visual acuity (EDTRS)
time frame: Weeks 0, 24, 48, 72
measure: Objective visual field by chromatic multifocal pupillometer
time frame: Weeks 0, 24,48,72
description: Objective evaluation of 76 point visual field using a chromatic multifocal pupillometer.
arm group label: Alga Dunaliella Bardawil 9-cis beta Carotene Rich Powder
arm group type: Experimental
description: 50 patients will receive first the capsules containing the alga Dunaliella Bardawil 9-cis beta-Carotene rich powder and after 24 weeks of washout period will receive capsule containing placebo (Starch).
arm group label: Placebo (Starch)
arm group type: Placebo Comparator
description: The other 50 Patients will receive first the placebo (Starch) capsules and after 24 weeks of washout period will receive capsules containing the alga Dunaliella Bardawil 9-cis beta-Carotene rich powder .
intervention type: Dietary Supplement
intervention name: Alga Dunaliella Bardawil
arm group label: Alga Dunaliella Bardawil 9-cis beta Carotene Rich Powder
arm group label: Placebo (Starch)
intervention type: Other
intervention name: Placebo (starch)
arm group label: Alga Dunaliella Bardawil 9-cis beta Carotene Rich Powder
arm group label: Placebo (Starch)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ygal Rotenstreich, Dr.
role: Principal Investigator
affiliation: Sheba Medical Center
facility: 
country: Israel
citation: 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.
PMID: 23700011
citation: 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.
PMID: 19955196
citation: Skaat A, Sher I, Kolker A, Elyasiv S, Rosenfeld E, Mhajna M, Melamed S, Belkin M, Rotenstreich Y. Pupillometer-based objective chromatic perimetry in normal eyes and patients with retinal photoreceptor dystrophies. Invest Ophthalmol Vis Sci. 2013 Apr 17;54(4):2761-70. doi: 10.1167/iovs.12-11127.
PMID: 23482470
responsible party type: Principal Investigator
investigator affiliation: Sheba Medical Center
investigator full name: Dr. Ygal Rotenstreich
investigator title: Director of Hereditary Retinal Diseases and Electrophysiology Clinic
mesh term: Retinitis
mesh term: Retinitis Pigmentosa