DHA and X-Linked Retinitis Pigmentosa

NCT00100230 | Completed Phase 2 Results DMC

• 4 other identifiers: 2543FD-R-0025435R01FD002543C-TX02-0704-0274
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

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

Conditions

Retinitis Pigmentosa; X-linked Genetic Diseases

Keywords

retina; electroretinography; clinical trial; docosahexaenoic acid; omega-3 fatty acid; x-linked inheritance

Outcome Measures

Primary Outcomes (1)

• Rate of LOSS of 31 Hertz Cone Electroretinographic Function

  Hypothesis #1: Elevation of red blood cell-docosahexaenoic acid levels will slow the progressive loss of 31 hertz cone electroretinographic response in this 4-year trial.

  4 years

Secondary Outcomes (1)

• Rate of LOSS of Rod Electroretinographic Function

  4 years

Other Outcomes (1)

• Loss of Peripheral Visual Fields

  4 years

Study Arms (2)

1.

EXPERIMENTAL

Oral Docosahexaenoic acid, dosage based on body weight

Drug: docosahexaenoic acid OR corn/soy oil placebo

2

PLACEBO COMPARATOR

corn/soy oil placebo; oil not containing DHA...dosage based on body weight

Drug: docosahexaenoic acid OR corn/soy oil placebo

Interventions

docosahexaenoic acid OR corn/soy oil placebo DRUG

daily intake of DHA based on body weight or corn/soy oil placebo(oil not containing DHA; 4 year trial

Also known as: DHA; omega-3 fatty acid, OR RANDOMIZED TO corn/soy oil placebo

1.; 2

Eligibility Criteria

• Age: 7 Years - 32 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Retina Foundation of the Southwest: lead
• Foundation Fighting Blindness: collaborator
• DSM Nutritional Products, Inc.: collaborator

Study Sites (1)

Retina Foundation of the Southwest

Dallas, Texas, 75231, United States

Location

Related Publications (5)

• 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.

  PMID: 24805262 RESULT

• 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.

  PMID: 25015354 RESULT

• 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.

  PMID: 26469750 DERIVED

• 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.

  PMID: 25342618 DERIVED

• 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.

  PMID: 23828615 DERIVED

Related Links

• website for Retina Foundation of the Southwest

MeSH Terms

Conditions

Retinitis Pigmentosa; Genetic Diseases, X-Linked

Interventions

Docosahexaenoic Acids; Fatty Acids, Omega-3

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Dystrophies; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fatty Acids, Unsaturated; Fatty Acids; Fish Oils; Oils

Limitations and Caveats

A lower than expected event rate for the primary outcome measure was the major trial limitation.

Results Point of Contact

• Title: Dennis Hoffman, Ph.D., Sr. Research Scientist
• Organization: Retina Foundation of the Southwest

dhoffman@retinafoundation.org

214-363-3911

Study Officials

• Dennis R. Hoffman, Ph.D.

  Retina Foundation of the Southwest

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Research Scientist (Retina Foundation of the Southwest)

Study Record Dates

• First Submitted: December 27, 2004
• First Posted: December 28, 2004
• Study Start: September 1, 2004
• Primary Completion: May 1, 2012
• Study Completion: August 1, 2014
• Last Updated: March 17, 2015
• Results First Posted: March 17, 2015

Record last verified: 2015-03

Locations

US (1)