Retinitis PigmentosaPhase 3NCT00000116
Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
A Phase 3 study testing Vitamin A and Docosahexaenoic acid in people with Retinitis Pigmentosa, run by Carol Weigel DiFranco at 1 site in United States.
Trial summary
The purpose of this trial is to determine whether a nutritional supplement in addition to vitamin A will slow the course of retinitis pigmentosa. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Retinitis Pigmentosa
- What is being tested?
- Vitamin A and Docosahexaenoic acid
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 221 participants
- Where
- 1 siteUnited States
- Study dates
- May 1996to Sep 2002
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Ocular Criteria:
- Retinitis Pigmentosa, typical (non-syndromic) forms Best corrected visual acuity Greater than or equal to (GE )20/100 HFA 30-2 total point score GE 250 dB (decibels) 30 (Hertz) Hz ERG cone amplitude GE 0.68 microvolts
- Dietary Criteria:
- Dark fish intake Less than or equal to (LE) five servings per week Dietary omega-3 fatty acid intake LE 0.41 g/d Preformed Vitamin A intake in diet and supplements LE 10,000 IU/d Supplement intake LE 5000 IU/d of Vitamin A and LE 30 IU/d Vitamin E Consumption LE 3 alcoholic beverages per day
- Medical and other criteria:
- Body Mass Index Less than (LT )40 and weight GE 5th percentile for age, sex, and height Serum retinol level LE 100 mg/dl and serum retinyl ester levels LE 380 nm/L Serum cholesterol level LT 300 mg/dL and serum triglyceride levels LT 400 mg/dL Agree not to know study capsule content
Who cannot join
- Ocular criteria:
- No confounding ocular disease
- Dietary criteria:
- No intake of cod liver oil or omega-3 capsules
- Medical and other criteria:
- Not pregnant or planning to become pregnant No clinically significant abnormal result on Complete Blood Count or serum liver function profile No other disease which might affect absorption or metabolism of DHA or Vitamin A
Trial locations and contacts
1 site in 1 country.
United States1 site
Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, 02114
About this study
Official title: Clinical Trial of Docosahexaenoic Acid (DHA) in Patients With Retinitis Pigmentosa Receiving Vitamin A Treatment
The purpose of this trial is to determine whether a nutritional supplement in addition to vitamin A will slow the course of retinitis pigmentosa.
Read the detailed description
Retinitis pigmentosa (RP) is a group of inherited retinal degenerations with a worldwide prevalence of approximately 1 in 4,000. Patients typically report night blindness and difficulty with midperipheral visual field in adolescence. As the condition progresses, they lose far peripheral visual field. Most patients have reductions in central vision by age 50 to 80 years. Based on electroretinograms (ERGs), the course of the disease can be slowed on average among adults on 15,000 IU/day of vitamin A palmitate. While conducting the trial on the effects of vitamin A on RP, it became apparent that another substance in the diet could be affecting the course of the disease. This prompted the present randomized, controlled trial.
This study is a randomized, controlled, double-masked trial with a planned duration of 5 years. Patients with the common forms of RP are assigned to either a test or a control group. All receive 15,000 IU/day of vitamin A palmitate in addition to either 1200 mg/d of docosahexaenoic acid or control capsules. Participants will not know the contents of the supplement or the group to which they have been assigned until the end of the trial. The main outcome measurement is the total point score on the Humphrey Field Analyzer (HFA). In addition, computer-averaged 30-Hz cone ERG amplitudes and visual acuity are measured annually.
- Conditions
- Retinitis Pigmentosa
- Being tested
- Vitamin A, Docosahexaenoic acid, Control fatty acid
- Medical subject headings
- Retinitis Pigmentosa
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin ADietary supplement
15000 IU/d as retinyl palmitate
Docosahexaenoic acidDietary supplement
1200 mg/d
Control fatty acidDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| Docosahexaenoic acid + Vitamin A | Experimental | Participants randomized to this arm received 1200 mg/d docosahexaenoic acid and 15000 IU/d Vitamin A as retinyl palmitate Receives: Dietary Supplement: Vitamin A; Dietary Supplement: Docosahexaenoic acid |
| Control fatty acid + Vitamin A | Placebo comparator | Patients randomized to this arm received 500 mg/d of fatty acid with no docosahexaenoic acid and 15000 IU/ Vitamin A as retinyl palmitate Receives: Dietary Supplement: Vitamin A; Dietary Supplement: Control fatty acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Humphrey Field Analyzer (HFA) total point score 30-2 program
Sum of points in Decibels of total points seen in 30-2 program. Higher scores = better vision/larger visual field
Measured: Annual percent change per year at each of 4 years of followup
Secondary outcomes (3)
Change in Humphrey Field Analyzer (HFA) total point score 30 -2 plus 30/60-2 programs combined
Sum of points in decibels of total points seen in 30-2 and 30/60-2 programs combined- Higher scores = better vision/ larger visual field
Measured: Annual percent change per year at each of four years of followup
Change in 30Hz Electroretinogram ( ERG) amplitude
Value in microvolts of response to 30hz ERG. Higher values = greater visual function
Measured: Annual percent change per year at each of four years of followup
Change in Early Treatment of Diabetic Retinopathy(EDTRS) Visual Acuity
Number of letters read per year. More letters read = better visual acuity
Measured: Change in number of letters read per year at each of four years of followup.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 1999 (estimated)
- Study startMay 1996
- Primary completionSep 2002
- Study completionSep 2002
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Retinitis PigmentosaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 221 participants (actual)
Sponsor and investigators
- Lead sponsor
- Carol Weigel DiFranco
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor-investigator, Carol Weigel DiFranco, National Eye Institute (NEI)
- Investigators
- Eliot Berson (Deceased), MD, Principal investigator, Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000116
- Sponsor's protocol ID
- NEI-12
- Status last verified
- Feb 2023
- First submitted
- 23 Sep 1999
- Last updated
- 8 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Berson EL, Rosner B, Sandberg MA, Hayes KC, Nicholson BW, Weigel-DiFranco C, Willett W. A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. Arch Ophthalmol. 1993 Jun;111(6):761-72. doi: 10.1001/archopht.1993.01090060049022.
PubMed 8512476Berson EL, Rosner B, Sandberg MA, Weigel-DiFranco C, Moser A, Brockhurst RJ, Hayes KC, Johnson CA, Anderson EJ, Gaudio AR, Willett WC, Schaefer EJ. Clinical trial of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment. Arch Ophthalmol. 2004 Sep;122(9):1297-305. doi: 10.1001/archopht.122.9.1297.
PubMed 15364708Berson EL, Rosner B, Sandberg MA, Weigel-DiFranco C, Moser A, Brockhurst RJ, Hayes KC, Johnson CA, Anderson EJ, Gaudio AR, Willett WC, Schaefer EJ. Further evaluation of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment: subgroup analyses. Arch Ophthalmol. 2004 Sep;122(9):1306-14. doi: 10.1001/archopht.122.9.1306.
PubMed 15364709Comander J, Weigel DiFranco C, Sanderson K, Place E, Maher M, Zampaglione E, Zhao Y, Huckfeldt RM, Bujakowska KM, Pierce E. Natural history of retinitis pigmentosa based on genotype, vitamin A/E supplementation, and an electroretinogram biomarker. JCI Insight. 2023 Aug 8;8(15):e167546. doi: 10.1172/jci.insight.167546.
PubMed 37261916
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Trial of Docosahexaenoic Acid (DHA) in Patients With Retinitis Pigmentosa Receiving Vitamin A Treatment
- ClinicalTrials.gov ID
- NCT00000116
- Acronym / sponsor ID
- NEI-12
- Conditions
- Retinitis Pigmentosa
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 221 participants (actual)
- Lead sponsor
- Carol Weigel DiFrancoUS National Institutes of Health
- Study start
- May 1996 (actual)
- Primary completion
- Sep 2002 (actual)
- Study completion
- Sep 2002 (actual)
- First posted
- 24 Sep 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this trial is to determine whether a nutritional supplement in addition to vitamin A will slow the course of retinitis pigmentosa.
Detailed description
Retinitis pigmentosa (RP) is a group of inherited retinal degenerations with a worldwide prevalence of approximately 1 in 4,000. Patients typically report night blindness and difficulty with midperipheral visual field in adolescence. As the condition progresses, they lose far peripheral visual field. Most patients have reductions in central vision by age 50 to 80 years. Based on electroretinograms (ERGs), the course of the disease can be slowed on average among adults on 15,000 IU/day of vitamin A palmitate. While conducting the trial on the effects of vitamin A on RP, it became apparent that another substance in the diet could be affecting the course of the disease. This prompted the present randomized, controlled trial.
This study is a randomized, controlled, double-masked trial with a planned duration of 5 years. Patients with the common forms of RP are assigned to either a test or a control group. All receive 15,000 IU/day of vitamin A palmitate in addition to either 1200 mg/d of docosahexaenoic acid or control capsules. Participants will not know the contents of the supplement or the group to which they have been assigned until the end of the trial. The main outcome measurement is the total point score on the Humphrey Field Analyzer (HFA). In addition, computer-averaged 30-Hz cone ERG amplitudes and visual acuity are measured annually.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Docosahexaenoic acid + Vitamin A | Experimental | Dietary Supplement: Vitamin A, Dietary Supplement: Docosahexaenoic acidParticipants randomized to this arm received 1200 mg/d docosahexaenoic acid and 15000 IU/d Vitamin A as retinyl palmitate |
| Control fatty acid + Vitamin A | Placebo comparator | Dietary Supplement: Vitamin A, Dietary Supplement: Control fatty acidPatients randomized to this arm received 500 mg/d of fatty acid with no docosahexaenoic acid and 15000 IU/ Vitamin A as retinyl palmitate |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Retinitis Pigmentosa, typical (non-syndromic) forms Best corrected visual acuity Greater than or equal to (GE )20/100 HFA 30-2 total point score GE 250 dB (decibels) 30 (Hertz) Hz ERG cone amplitude GE 0.68 microvolts
- Dark fish intake Less than or equal to (LE) five servings per week Dietary omega-3 fatty acid intake LE 0.41 g/d Preformed Vitamin A intake in diet and supplements LE 10,000 IU/d Supplement intake LE 5000 IU/d of Vitamin A and LE 30 IU/d Vitamin E Consumption LE 3 alcoholic beverages per day
- Body Mass Index Less than (LT )40 and weight GE 5th percentile for age, sex, and height Serum retinol level LE 100 mg/dl and serum retinyl ester levels LE 380 nm/L Serum cholesterol level LT 300 mg/dL and serum triglyceride levels LT 400 mg/dL Agree not to know study capsule content
Key exclusion criteria (6 listed)
- No confounding ocular disease
- No intake of cod liver oil or omega-3 capsules
- Not pregnant or planning to become pregnant No clinically significant abnormal result on Complete Blood Count or serum liver function profile No other disease which might affect absorption or metabolism of DHA or Vitamin A
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin A15000 IU/d as retinyl palmitate | Dietary supplement | Control fatty acid + Vitamin A, Docosahexaenoic acid + Vitamin A |
| Docosahexaenoic acid1200 mg/d | Dietary supplement | Docosahexaenoic acid + Vitamin A |
| Control fatty acid | Dietary supplement | Control fatty acid + Vitamin A |
Primary outcome
Change in Humphrey Field Analyzer (HFA) total point score 30-2 program
Time frame: Annual percent change per year at each of 4 years of followup
Sum of points in Decibels of total points seen in 30-2 program. Higher scores = better vision/larger visual field
3 secondary outcomes
Change in Humphrey Field Analyzer (HFA) total point score 30 -2 plus 30/60-2 programs combined
Time frame: Annual percent change per year at each of four years of followup
Change in 30Hz Electroretinogram ( ERG) amplitude
Time frame: Annual percent change per year at each of four years of followup
Change in Early Treatment of Diabetic Retinopathy(EDTRS) Visual Acuity
Time frame: Change in number of letters read per year at each of four years of followup.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2023.
- Background: PubMed 8512476Berson EL, Rosner B, Sandberg MA, Hayes KC, Nicholson BW, Weigel-DiFranco C, Willett W. A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. Arch Ophthalmol. 1993 Jun;111(6):761-72. doi: 10.1001/archopht.1993.01090060049022.
- Results publication: PubMed 15364708Berson EL, Rosner B, Sandberg MA, Weigel-DiFranco C, Moser A, Brockhurst RJ, Hayes KC, Johnson CA, Anderson EJ, Gaudio AR, Willett WC, Schaefer EJ. Clinical trial of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment. Arch Ophthalmol. 2004 Sep;122(9):1297-305. doi: 10.1001/archopht.122.9.1297.
- Results publication: PubMed 15364709Berson EL, Rosner B, Sandberg MA, Weigel-DiFranco C, Moser A, Brockhurst RJ, Hayes KC, Johnson CA, Anderson EJ, Gaudio AR, Willett WC, Schaefer EJ. Further evaluation of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment: subgroup analyses. Arch Ophthalmol. 2004 Sep;122(9):1306-14. doi: 10.1001/archopht.122.9.1306.
- Derived from this study: PubMed 37261916Comander J, Weigel DiFranco C, Sanderson K, Place E, Maher M, Zampaglione E, Zhao Y, Huckfeldt RM, Bujakowska KM, Pierce E. Natural history of retinitis pigmentosa based on genotype, vitamin A/E supplementation, and an electroretinogram biomarker. JCI Insight. 2023 Aug 8;8(15):e167546. doi: 10.1172/jci.insight.167546.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eliot Berson (Deceased), MD principal investigator
Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vitamin A and Docosahexaenoic acid in people with Retinitis Pigmentosa, run by Carol Weigel DiFranco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Humphrey Field Analyzer (HFA) total point score 30-2 program (time frame: Annual percent change per year at each of 4 years of followup). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00000116, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2023.