The Effect of Oral Administration of 9-cis Rich Powder of the Alga Dunaliella Bardawil on Visual Functions in Adolescent Patients With Retinitis Pigmentosa

Official title

The Effect of Oral Administration of 9-cis β Carotene Rich Powder of the Alga Dunaliella Bardawil on Visual Functions in Adolescent Patients With Retinitis Pigmentosa

Overview

The aim of this study is to determine whether 9-cis-beta Caroten rich D. Brdawiil extract is effective in the treatment of retinitis pigmentosa in adolescent patients.

Detailed description

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 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.

As a natural extension of this study we will perform a double-masked, randomized, crossover, placebo-controlled study for adolescent patients. Longer treatment duration will be tested: a 24 week treatment with either the 9-cis β-carotene-rich capsules or placebo followed by an additional a 24 week treatment with the other capsules and a wash-out period of 24 weeks between this two type of treatments. We predict that with this study design a maximal/increased therapeutic effect as well as efficient washout will be achieved.

Interventions

• Dietary supplement Alga Dunaliella Bardawil powder
  9 cis beta carotene rich Alga Dunaliella Bardawil powder
• Dietary supplement Placebo:Starch
  Starch powder

Primary outcome measures

• Mean binocular maximal scotopic electroretinogram b-wave response [Time frame: up to weeks 72]

Secondary outcome measures (5)

• The area within the Dark adapted chromatic Goldamann Visual field in isopters in cm2 [Time frame: On weeks 0, 24, 48, 72]
• The area within Goldamann Visual field in isopters in cm2 [Time frame: On weeks 0, 24, 48, 72]
• Mean binocular maximal photopic electroretinogram b-wave response [Time frame: On weeks 0, 24, 48, 72]
• Best-corrected visual acuity (EDTRS) [Time frame: On weeks 0, 24, 48, 72]
• Objective visual field by chromatic multifocal pupillometer [Time frame: On weeks 0,24,48,72]

Eligibility criteria

Inclusion criteria

• Written informed consent to participate in the study.
• Adolescent 12-18 years old.
• Electroretinogram (ERG) responses compatible with the diagnosis of Retinitis Pigmentosa

Exclusion criteria

• Currently a smoker
• Current use of vitamin A/ β-carotene supplements
• 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
• Females 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Israel · 1 center

• Goldschleger Eye Research Institute, Sheba Medical Center, — Tel Litwinsky

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. PMID 23700011
• 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
• 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
• Schwartz SG, Wang X, Chavis P, Kuriyan AE, Abariga SA. Vitamin A and fish oils for preventing the progression of retinitis pigmentosa. Cochrane Database Syst Rev. 2020 Jun 18;6(6):CD008428. doi: 10.1002/14651858.CD008428.pub3. PMID 32573764

Identifiers

NCT: NCT02018692 · SHEBA-13-9579-YR-CTIL

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗