Trial Outcomes & Findings for Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A (NCT NCT00346333)

NCT ID: NCT00346333

Last Updated: 2014-01-31

Results Overview

Sum of visual field sensitivity readings in decibel(dB) to a size V target out to the 30 degree meridian in each direction of the visual field. The value presented represents annual change in dB over 4 years.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 240 participants
• Primary outcome timeframe: assessed at each of 4 annual visits after baseline
• Results posted on: 2014-01-31

Participant Flow

We performed screening examinations in the Berman-Gund Laboratory at the Massachusetts Eye & Ear Infirmary, Boston Massachusetts from July 15, 2003 to October 28, 2004.

We screened patients for eligibility according to ocular, dietary, and medical criteria & performed a baseline examination on eligible patients within 8 weeks. At the baseline visit patients were randomized to 1 of 2 groups taking into account genetic type and initial serum lutein level (<= 6.4 micrograms/deciliter (mg/dL) or > 6.4 mg/dL).

Participant milestones

Measure	Control Plus Vitamin A cornstarch control plus 15,000 IU Vitamin A palmitate daily	Lutein Plus Vitamin A 12mg Lutein plus 15,000 IU Vitamin A palmitate daily
Overall Study STARTED	121	119
Overall Study COMPLETED	116	111
Overall Study NOT COMPLETED	5	8

Reasons for withdrawal

Measure	Control Plus Vitamin A cornstarch control plus 15,000 IU Vitamin A palmitate daily	Lutein Plus Vitamin A 12mg Lutein plus 15,000 IU Vitamin A palmitate daily
Overall Study Death	1	0
Overall Study unwilling or unable to continue	4	8

Baseline Characteristics

Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A

Baseline characteristics by cohort

Measure	Control Plus Vitamin A n=121 Participants cornstarch control plus 15,000IU Vitamin A palmitate daily	Lutein Plus Vitamin A n=119 Participants 12mg Lutein plus 15,000IU Vitamin A palmitate daily	Total n=240 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	121 Participants n=5 Participants	119 Participants n=7 Participants	240 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	38 years STANDARD_DEVIATION 1.0 • n=5 Participants	40 years STANDARD_DEVIATION 1.0 • n=7 Participants	39 years STANDARD_DEVIATION 1.0 • n=5 Participants
Sex: Female, Male Female	51 Participants n=5 Participants	58 Participants n=7 Participants	109 Participants n=5 Participants
Sex: Female, Male Male	70 Participants n=5 Participants	61 Participants n=7 Participants	131 Participants n=5 Participants
Age of participants by 10-year age groups 18-29 years of age	34 Participants n=5 Participants	25 Participants n=7 Participants	59 Participants n=5 Participants
Age of participants by 10-year age groups 30-39 years of age	26 Participants n=5 Participants	35 Participants n=7 Participants	61 Participants n=5 Participants
Age of participants by 10-year age groups 40-49 years of age	41 Participants n=5 Participants	36 Participants n=7 Participants	77 Participants n=5 Participants
Age of participants by 10-year age groups 50-60 years of age	20 Participants n=5 Participants	23 Participants n=7 Participants	43 Participants n=5 Participants
Genetic type Dominant	30 participants n=5 Participants	28 participants n=7 Participants	58 participants n=5 Participants
Genetic type Recessive	20 participants n=5 Participants	19 participants n=7 Participants	39 participants n=5 Participants
Genetic type X-Linked	8 participants n=5 Participants	7 participants n=7 Participants	15 participants n=5 Participants
Genetic type Isolate	58 participants n=5 Participants	60 participants n=7 Participants	118 participants n=5 Participants
Genetic type Undetermined	5 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants

PRIMARY outcome

Timeframe: assessed at each of 4 annual visits after baseline

Population: Intention to treat analysis;sample of 215 patients with all 4 years of followup and reliable, non missing data at all 4 years was analyzed. Eyes with an initial 30-2 total point score \>= 250 dB were included.The eye was the unit of analysis. Each patient contributed 2,1, or 0 eyes with non-missing data.

Sum of visual field sensitivity readings in decibel(dB) to a size V target out to the 30 degree meridian in each direction of the visual field. The value presented represents annual change in dB over 4 years.

Outcome measures

Measure	Control Plus Vitamin A n=110 Participants cornstarch control plus 15,000 IU Vitamin A palmitate daily	Lutein Plus Vitamin A n=105 Participants 12mg Lutein plus 15,000 IU Vitamin A palmitate daily
Central Visual Field (vf) Change Assessed Using the 30-2 Program of the Humphrey Field Analyzer (HFA).	-51.5 annual change in db vf sensitivity Standard Error 3.2	-49.6 annual change in db vf sensitivity Standard Error 3.3

SECONDARY outcome

Timeframe: assessed at each of 4 annual visits after baseline

Population: This was an intention to treat analysis;lower sample sizes for this endpoint reflect instances where test results were not available for this outcome variable.The ability to perform this test was not a criterion for study entry.Eyes with an initial score ≥ 10 were included. Values were set to zero for all visits after an initial value of zero.

Sum of visual field sensitivity readings in dB to a size V target from the 30 degree meridian to the 60 degree meridian in each direction of the visual field. The value presented represents annual change in dB over 4 years.

Outcome measures

Measure	Control Plus Vitamin A n=82 Participants cornstarch control plus 15,000 IU Vitamin A palmitate daily	Lutein Plus Vitamin A n=81 Participants 12mg Lutein plus 15,000 IU Vitamin A palmitate daily
Mid-peripheral Field Change Assessed With the 60-4 Program of the Humphrey Field Analyzer.	-34.1 annual change in dB vf sensitivity Standard Error 3.0	-26.6 annual change in dB vf sensitivity Standard Error 3.1

SECONDARY outcome

Timeframe: assessed at each of 4 annual visits after baseline

Population: This was an intention to treat analysis. A total field was calculated for each eye using the 30-2 and 60-4 conditions after applying the eligibility criteria for each component. Total field for a given eye was not calculated if either was missing. The unit of analysis was the eye.Each patient contributed 2, 1, or 0 eyes with non-missing data.

Sum of visual field sensitivity readings in dB to a size V target obtained with the 30-2 and 60-4 programs of the Humphrey Field Analyzer combined for those patients on whom both measures were available.

Outcome measures

Measure	Control Plus Vitamin A n=79 Participants cornstarch control plus 15,000 IU Vitamin A palmitate daily	Lutein Plus Vitamin A n=78 Participants 12mg Lutein plus 15,000 IU Vitamin A palmitate daily
Total Field Change Assessed by the Combined 30-2 and 60-4 Programs of the Humphrey Field Analyzer.	-83.1 annual change in dB vf sensitivity Standard Error 6.2	-92.9 annual change in dB vf sensitivity Standard Error 5.7

SECONDARY outcome

Timeframe: assessed at each of 4 annual visits after baseline

Population: This was an intention to treat analysis;analyses of 30 Hz ERG data included those who had an initial amplitude of 0.68 microvolts or greater in at least 1 eye and data were censored when values declined to less than 0.34 microvolts. The unit of analysis was the eye.Each patient contributed 2,1,or 0 eyes with non-missing data.

Computer averaged 30 Hz ERG amplitudes in microvolts for those with initial amplitudes of >= 0.68 microvolts. Presented on the ln scale.

Outcome measures

Measure	Control Plus Vitamin A n=77 Participants cornstarch control plus 15,000 IU Vitamin A palmitate daily	Lutein Plus Vitamin A n=79 Participants 12mg Lutein plus 15,000 IU Vitamin A palmitate daily
Annual Change in 30 Hertz(Hz)Electroretinogram(ERG )Amplitude in Natural Log (ln) Microvolts/yr Over a 4 Year Period.	-0.08 ln (microvolts)/year Standard Error 0.12	-0.09 ln (microvolts)/year Standard Error 0.01

SECONDARY outcome

Timeframe: assessed at each of 4 annual visits after baseline

Population: This was an intention to treat analysis and included all reliable, non-missing values. The unit of analysis was the eye.Each patient contributed 2,1, or 0 eyes with non-missing data.

Annual change in number of letters read.

Outcome measures

Measure	Control Plus Vitamin A n=111 Participants cornstarch control plus 15,000 IU Vitamin A palmitate daily	Lutein Plus Vitamin A n=110 Participants 12mg Lutein plus 15,000 IU Vitamin A palmitate daily
Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity	-0.49 Change in letters read per year Standard Error 0.12	-0.53 Change in letters read per year Standard Error 0.12

Adverse Events

Control Plus Vitamin A

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Lutein Plus Vitamin A

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Control Plus Vitamin A n=121 participants at risk Daily intake of cornstarch control plus 15,000IU Vitamin A palmitate	Lutein Plus Vitamin A n=119 participants at risk 12mg Lutein plus 15,000IU Vitamin A daily.
Injury, poisoning and procedural complications Death	0.83% 1/121 • Number of events 1 • Adverse events were monitored throughout the entire study period. This monitoring included questionnaires at annual visits and over the telephone at 3 month intervals, blood tests at annual visits,and evaluations by the consulting internist if needed.	0.00% 0/119 • Adverse events were monitored throughout the entire study period. This monitoring included questionnaires at annual visits and over the telephone at 3 month intervals, blood tests at annual visits,and evaluations by the consulting internist if needed.
Metabolism and nutrition disorders Elevated liver enzymes	0.00% 0/121 • Adverse events were monitored throughout the entire study period. This monitoring included questionnaires at annual visits and over the telephone at 3 month intervals, blood tests at annual visits,and evaluations by the consulting internist if needed.	0.84% 1/119 • Number of events 1 • Adverse events were monitored throughout the entire study period. This monitoring included questionnaires at annual visits and over the telephone at 3 month intervals, blood tests at annual visits,and evaluations by the consulting internist if needed.

Other adverse events

Adverse event data not reported

Additional Information

Eliot L. Berson, M.D.

Harvard Medical School

Phone: 617-573-3600

Email: marilyn_sullivan@meei.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place