The Effect of Oral Administration of 9-cis β Carotene Rich Powder of the Alga Dunaliella Bardawil

Study Overview
=================
Brief Summary
-----------------
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.

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

Conditions
-----------------
Retinitis Pigmentosa

Intervention / Treatment
-----------------
* Dietary Supplement: Alga Dunaliella Bardawil
* Other: Placebo (starch)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 Exclusion Criteria: Current smokers. Current use of Vitamin A/ beta carotene supplements. Active arterial disease within 3 months of study entry such as unstable angina, myocardial infarction, transient ischemic attack (TIA), stroke, and coronary artery bypass graft (CABG) surgery. History of malignancy, except basal or squamous cell skin carcinoma. Pregnant women, women who are breast feeding, and women of childbearing potential who are not using chemical or mechanical contraception. Uncontrolled hypertension defined as either resting diastolic blood pressure of >95mmHg (taken from the mean of 3 readings) or resting systolic blood Pressure of > 180 mmHg. History of alcohol abuse or drug abuse, or both. Patient plans to engage in vigorous exercise or an aggressive diet regimen. Uncontrolled endocrine or metabolic disease. Participation in another investigational drug study within 4 weeks of entry into this study. Serious or unstable medical or psychological condition that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study. Subject whose hormone replacement therapy (HRT) or oral contraceptive therapy (OCT) was initiated within the 3 month prior to enrollment.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Alga vs. placebo
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alga Dunaliella Bardawil 9-cis beta Carotene Rich Powder<br>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). | Dietary Supplement: Alga Dunaliella Bardawil<br> <br> Other: Placebo (starch)<br> <br> |
| Placebo Comparator: Placebo (Starch)<br>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 . | Dietary Supplement: Alga Dunaliella Bardawil<br> <br> Other: Placebo (starch)<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean binocular maximal scotopic electroretinogram b-wave response | 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. | At weeks 0, 24,48,72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The area within the Dark adapted chromatic Goldamann Visual field in isopters in cm2 | 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. | at weeks 0, 24, 48, 72 | 
| The area within Goldamann Visual field in isopters in cm2 | Kinetic visual field will be recorded in both eyes. Area of vision within the isopter will be measured by software in cm2. | at weeks 0, 24, 48, 72 | 
| Mean binocular maximal photopic electroretinogram b-wave response | 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. | Weeks 0, 24, 48, 72 | 
| Best-corrected visual acuity (EDTRS) |  | Weeks 0, 24, 48, 72 |