Clinical trial NCT00100230: DHA and X-Linked Retinitis Pigmentosa
Official title: Investigation of Effectiveness and Safety of High Dose Docosahexaenoic Acid (DHA) in X-Linked Retinitis Pigmentosa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Retinitis Pigmentosa
X-linked Genetic Diseases
Keywords: retina
electroretinography
clinical trial
docosahexaenoic acid
omega-3 fatty acid
x-linked inheritance
Lead sponsor: Retina Foundation of the Southwest
Sponsor class: OTHER
Collaborators: name: Foundation Fighting Blindness
name: DSM Nutritional Products, Inc.
First posted: 2004-12-28
Enrollment: 78
Sex: MALE
Minimum age (years): 7
Maximum age (years): 32
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Purpose:

Retinitis pigmentosa (RP) is characterized by progressive loss of visual function due to specific genetic mutations. This trial is focused on patients with one of the most severe forms of the disease, X-linked inherited RP (XLRP). This disease is characterized by early onset (typically loss of night vision as a child) followed by loss of peripheral vision as a teenager and young adult. There is no male-to-male transmission of the disease in the family.

There is no cure for RP and treatment options are limited. Two clinical trials have not found a benefit from nutritional supplementation with the long-chain polyunsaturated fatty acid, docosahexaenoic acid (DHA), at low daily doses although there is evidence that it slows disease progression in certain instances. In this clinical trial, we propose that a high dose nutritional DHA supplement will slow the loss of visual function and preserve usable vision in patients with XLRP.

This study is a 4-year placebo-controlled randomized clinical trial meaning that patients have a 50-50 chance of receiving placebo or experimental treatment. A total of 66 patients will be enrolled; 33 will receive placebo and 33 will receive the treatment. Entry criteria include diagnosis of XLRP by an ophthalmologist, age 7 to 32 years, male, sufficient visual function such that disease progression can be followed for the entire duration of the trial, and a willingness to visit the testing site (Dallas, TX) once a year.

Annual visual function testing includes ETDRS visual acuity, full-field and multifocal electroretinography (ERG), static peripheral visual fields, and fundus photography. Cone ERG function is the primary outcome measure.

Funding Source - FDA, Foundation Fighting Blindness, DSM Nutritionals

Detailed description: Location \& Contact Information:

Retina Foundation of the Southwest, 9600 N. Central Expressway, Suite 200, Dallas, TX 75231 Contact: Dr. D. Hoffman (dhoffman@retinafoundation.org) or Dr. D. Birch (dbirch@retinafoundation.org).

Eligibility criteria: Inclusion Criteria:

* Diagnosis of RP by a retinal specialist
* Clinical diagnosis consistent with X-linked inheritance
* Enrolling minors and young adults (early onset of X-linked disease; ages 7 to 32)
* Measurable cone ERG responses --patients with less than 0.64 microvolt response to 31-Hz flicker will be excluded as they are more likely to become undetectable during the study
* Both eyes must meet entry criteria as both will be tested (i.e., no cataracts requiring surgery or retinal detachments).
* Media clarity sufficient for fundus photography
* Able to return to study site at yearly intervals
* Willing to supply blood samples at 6-month intervals
* Judiciously take the placebo or DHA supplement for the 4-year study duration
* Patient/parent/guardian understands and signs consent form.

Exclusion Criteria:

* Excessive fish consumption (e.g., cold water fish such as salmon, tuna, sardines) and/or fish oil supplementation (or other oil containing DHA)
* Baseline RBC-DHA levels showing evidence of supplementation (a typical level of RBC-DHA in normals is about 3.8%)
* Chronic metabolic disease that may interfere with fatty acid metabolism or require anti-coagulant medication

No ethnic or racial groups will be excluded.

Primary outcomes:
measure: Rate of LOSS of 31 Hertz Cone Electroretinographic Function
timeFrame: 4 years
Secondary outcomes:
measure: Rate of LOSS of Rod Electroretinographic Function
timeFrame: 4 years
Other outcomes:
measure: Loss of Peripheral Visual Fields
timeFrame: 4 years
Locations:
city: Dallas
country: United States
facility: Retina Foundation of the Southwest
state: Texas
Study officials:
affiliation: Retina Foundation of the Southwest
name: Dennis R. Hoffman, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hoffman DR, Hughbanks-Wheaton DK, Pearson NS, Fish GE, Spencer R, Takacs A, Klein M, Locke KG, Birch DG. Four-year placebo-controlled trial of docosahexaenoic acid in X-linked retinitis pigmentosa (DHAX trial): a randomized clinical trial. JAMA Ophthalmol. 2014 Jul;132(7):866-73. doi: 10.1001/jamaophthalmol.2014.1634.
citation: Hughbanks-Wheaton DK, Birch DG, Fish GE, Spencer R, Pearson NS, Takacs A, Hoffman DR. Safety assessment of docosahexaenoic acid in X-linked retinitis pigmentosa: the 4-year DHAX trial. Invest Ophthalmol Vis Sci. 2014 Jul 11;55(8):4958-66. doi: 10.1167/iovs.14-14437.
citation: Hoffman DR, Hughbanks-Wheaton DK, Spencer R, Fish GE, Pearson NS, Wang YZ, Klein M, Takacs A, Locke KG, Birch DG. Docosahexaenoic Acid Slows Visual Field Progression in X-Linked Retinitis Pigmentosa: Ancillary Outcomes of the DHAX Trial. Invest Ophthalmol Vis Sci. 2015 Oct;56(11):6646-53. doi: 10.1167/iovs.15-17786.
citation: Cai CX, Locke KG, Ramachandran R, Birch DG, Hood DC. A comparison of progressive loss of the ellipsoid zone (EZ) band in autosomal dominant and x-linked retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2014 Oct 23;55(11):7417-22. doi: 10.1167/iovs.14-15013.
citation: Birch DG, Locke KG, Wen Y, Locke KI, Hoffman DR, Hood DC. Spectral-domain optical coherence tomography measures of outer segment layer progression in patients with X-linked retinitis pigmentosa. JAMA Ophthalmol. 2013 Sep;131(9):1143-50. doi: 10.1001/jamaophthalmol.2013.4160.