Clinical trial NCT02018692: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Retinitis Pigmentosa
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
First posted: 2013-12-23
Enrollment: 30
Sex: ALL
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

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

Primary outcomes:
measure: Mean binocular maximal scotopic electroretinogram b-wave response
timeFrame: up to weeks 72
Secondary outcomes:
measure: The area within the Dark adapted chromatic Goldamann Visual field in isopters in cm2
timeFrame: On weeks 0, 24, 48, 72
measure: The area within Goldamann Visual field in isopters in cm2
timeFrame: On weeks 0, 24, 48, 72
measure: Mean binocular maximal photopic electroretinogram b-wave response
timeFrame: On weeks 0, 24, 48, 72
measure: Best-corrected visual acuity (EDTRS)
timeFrame: On weeks 0, 24, 48, 72
measure: Objective visual field by chromatic multifocal pupillometer
timeFrame: On weeks 0,24,48,72
Other outcomes:
Locations:
city: Tel Hashomer
country: Israel
facility: Goldschleger Eye Research Institute, Sheba Medical Center,
Study officials:
affiliation: Goldschleger Eye Research Institute, Sheba Medical Center, Tel Hashomer
name: Ygal Rotenstreich, MD
role: PRINCIPAL_INVESTIGATOR
References:
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: 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: 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: 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.