Age-related Macular Degeneration
Conditions
Keywords
lutein, zeaxanthin, age-related macular degeneration, supplementation, macular pigment optical density, visual function, serum concentration
Brief summary
This study is to investigate the protective effects of supplemental lutein and zeaxanthin on early age-related macular degeneration (AMD) patients in China.
Detailed description
Early age-related macular degeneration (AMD) is an early hallmark of irreversible vision impairment accompanying with senescence of macular. Given the fact in treatment, prevention strategy is thought to be an efficient and robust approach to diminish early AMD patients in low-income countries, however, feasible cocktail provision in most developing nations remain mysteries. Here we proposed an effective cocktail treatment with different amounts of lutein and zeaxanthin could increase the macular pigment optical density (MPOD) and serum xanthophylls concentrations among randomized Chinese AMD patients; and might improve visual function measured by visual performance indices such as best-spectacle corrected visual acuity (BSCVA), contrast sensitivity (CSF), flash recovery time (FRT), multifocal electroretinogram (mfERG) and microperimetry.
Interventions
DIETARY_SUPPLEMENTplacebo
Placebo, one gelatine capsule containing starch per day, for 96 weeks
DIETARY_SUPPLEMENTlow lutein
one gelatine capsule containing 10mg lutein per day, for 96 weeks
DIETARY_SUPPLEMENThigh lutein
one gelatine capsule containing 20mg lutein per day, for 96 weeks
DIETARY_SUPPLEMENTlutein plus zeaxanthin
one gelatine capsule containing 10mg lutein and 10mg zeaxanthin per day, for 96 weeks
DIETARY_SUPPLEMENThigh zeaxanthin
one gelatine capsule containing 10mg zeaxanthin per day, for 48 weeks
DIETARY_SUPPLEMENTzeaxanthin plus lutein
one gelatine capsule containing 10 mg lutein and 15 mg zeaxanthin per day, for 48 weeks
Sponsors
Peking University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* aged over 50 years, Chinese of the Han nationality * diagnosed as age-related macular degeneration * did not take lutein or zeaxanthin supplements in the past half a year * good general health * corrected visual acuity above 0.25 (20/80) * did not take optical laser or medical treatments
Exclusion criteria
* had other ocular diseases, such as glaucoma, macular pucker, optic neuropathy, diabetic retinopathy etc. * had nervous system diseases, stroke, Type I diabetes * had diseases effected nutrients absorption, such as Crohn' s disease * had turbid ocular media or transplanted intraocular lenses * reported abnormal digestive condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | at baseline and 24 weeks, 48 weeks, 2 years during the intervention | Macular pigment is found in the center of the retina known as the macula and is made up of the carotenoids lutein and zeaxanthin. This pigment serves to protect the macula from harmful blue light. The MPOD ranges from 0 to 1, with higher scores corresponding with greater density (protection). The autofluorescence picture of subject's macular was analyzed for MPOD values. 4 participants was excluded during the analysis since they did not finish the intervention. Three did not finish the follow up, while one died from breast cancer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | at baseline and 24 weeks, 48 weeks, 2 years during the intervention | best-spectacle corrected visual acuity (BSCVA) measured by ETDRS chart at baseline and 24 weeks, 48 weeks, 2 years during the intervention. Four participants was excluded during the analysis since they did not finish the intervention. Three did not finish the follow up, while one died from breast cancer. |
| Changes of Contrast Sensitivity (CSF) Measured by CSV-100 During the Intervention | at baseline, 24, 48 weeks and 2 years during the intervention | — |
| Changes of Flash Recovery Time (FRT) Measured by MDD-2 Macular Adaptometer | at baseline, 24, 48 weeks and 2 years during the intervention | Flash recovery time (FRT) was measured by MDD-2 macular adaptometer at baseline, 24, 48 and 96 weeks |
| Changes of Serum Xanthophylls Concentrations During the Intervention | at baseline and 4, 12, 24 and 48 weeks during the intervention | Changes of serum xanthophylls concentrations measured by high performance liquid chromatograph (HPLC)at baseline and 4, 12, 24 and 48 weeks during the first 48 weeks of intervention.Four participants was excluded during the analysis since they did not finish the intervention. Three did not finish the follow up, while one died from breast cancer. |
| Changes From Baseline in Microperimetry (MP) During the Intervention | at baseline, 24, 48 weeks and 2 years during the intervention | Microperimetry (MP) was measured by the MP1 Microperimeter |
| Changes of Food Pattern From Baseline by Food Frequency Questionnaire During the Intervention | at baseline, 24, 48 weeks and 2 years | — |
| Changes From Baseline in Multifocal Electroretinogram (mfERG) at 48 Weeks | at baseline and 48 weeks during the intervention | — |
Countries
China
Participant flow
Pre-assignment details
We added High Zeaxanthin and High Lutein Zeaxanthin Arms at the seconde year for additional information on the effect of zeaxanthin on MPOD and visual functions. Therefore, we did not measure the changes of serum concentration, and only measured the change of MOPD and visual functions at baseline and 48 weeks, in the two new groups.
Participants by arm
| Arm | Count |
|---|---|
| Low Lutein low lutein group
low lutein: one gelatine capsule containing 10mg lutein per day, for 96 weeks | 26 |
| Placebo starch in hard shell gelatine capsules
placebo: Placebo, one gelatine capsule containing starch per day, for 96 weeks | 28 |
| High Lutein high lutein group
high lutein: one gelatine capsule containing 20mg lutein per day, for 96 weeks | 27 |
| Low Lutein Zeaxanthin lutein plus zeaxanthin group
lutein plus zeaxanthin: one gelatine capsule containing 10mg lutein and 10mg zeaxanthin per day, for 96 weeks | 27 |
| High Zeaxanthin zeaxanthin group
high zeaxanthin: one gelatine capsule containing 10mg zeaxanthin per day, for 48 weeks | 28 |
| High Lutein Zeaxanthin Zeaxanthin plus lutein group
zeaxanthin plus lutein: one gelatine capsule containing 10 mg lutein and 15 mg zeaxanthin per day, for 48 weeks | 28 |
| Total | 164 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Low Lutein | Placebo | High Lutein | Low Lutein Zeaxanthin | High Zeaxanthin | High Lutein Zeaxanthin | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 69.7 years STANDARD_DEVIATION 8.3 | 69.0 years STANDARD_DEVIATION 7.5 | 69.3 years STANDARD_DEVIATION 6.9 | 68.5 years STANDARD_DEVIATION 6.9 | 69.7 years STANDARD_DEVIATION 5.4 | 69.1 years STANDARD_DEVIATION 8.1 | 69.2 years STANDARD_DEVIATION 7.6 |
| Region of Enrollment China | 26 participants | 28 participants | 27 participants | 27 participants | 28 participants | 28 participants | 164 participants |
| Sex: Female, Male Female | 17 Participants | 17 Participants | 13 Participants | 15 Participants | 17 Participants | 15 Participants | 94 Participants |
| Sex: Female, Male Male | 9 Participants | 11 Participants | 14 Participants | 12 Participants | 11 Participants | 13 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 28 | 0 / 26 | 0 / 27 | 0 / 27 | 0 / 28 | 0 / 28 |
| serious Total, serious adverse events | 0 / 28 | 0 / 26 | 0 / 27 | 0 / 27 | 0 / 28 | 0 / 28 |
Outcome results
Primary
Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years
Macular pigment is found in the center of the retina known as the macula and is made up of the carotenoids lutein and zeaxanthin. This pigment serves to protect the macula from harmful blue light. The MPOD ranges from 0 to 1, with higher scores corresponding with greater density (protection). The autofluorescence picture of subject's macular was analyzed for MPOD values. 4 participants was excluded during the analysis since they did not finish the intervention. Three did not finish the follow up, while one died from breast cancer.
Time frame: at baseline and 24 weeks, 48 weeks, 2 years during the intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | baseline | 0.315 density units | Standard Deviation 0.144 |
| Placebo | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | 2 years | 0.324 density units | Standard Deviation 0.163 |
| Placebo | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | 48 weeks | 0.316 density units | Standard Deviation 0.11 |
| Placebo | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | 24 weeks | 0.310 density units | Standard Deviation 0.102 |
| Low Lutein | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | 2 years | 0.442 density units | Standard Deviation 0.127 |
| Low Lutein | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | 24 weeks | 0.353 density units | Standard Deviation 0.125 |
| Low Lutein | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | baseline | 0.307 density units | Standard Deviation 0.142 |
| Low Lutein | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | 48 weeks | 0.371 density units | Standard Deviation 0.188 |
| High Lutein | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | 48 weeks | 0.424 density units | Standard Deviation 0.142 |
| High Lutein | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | 2 years | 0.441 density units | Standard Deviation 0.133 |
| High Lutein | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | baseline | 0.315 density units | Standard Deviation 0.122 |
| High Lutein | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | 24 weeks | 0.395 density units | Standard Deviation 0.12 |
| Low Lutein Zeaxanthin | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | 24 weeks | 0.356 density units | Standard Deviation 0.15 |
| Low Lutein Zeaxanthin | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | 2 years | 0.383 density units | Standard Deviation 0.149 |
| Low Lutein Zeaxanthin | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | baseline | 0.320 density units | Standard Deviation 0.118 |
| Low Lutein Zeaxanthin | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | 48 weeks | 0.384 density units | Standard Deviation 0.125 |
| High Zeaxanthin | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | baseline | 0.327 density units | Standard Deviation 0.117 |
| High Zeaxanthin | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | 24 weeks | NA density units | — |
| High Zeaxanthin | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | 48 weeks | 0.384 density units | Standard Deviation 0.139 |
| High Zeaxanthin | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | 2 years | NA density units | — |
| High Lutein Zeaxanthin | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | 24 weeks | NA density units | — |
| High Lutein Zeaxanthin | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | baseline | 0.300 density units | Standard Deviation 0.168 |
| High Lutein Zeaxanthin | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | 2 years | NA density units | — |
| High Lutein Zeaxanthin | Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years | 48 weeks | 0.383 density units | Standard Deviation 0.179 |
Comparison: The null hypothesis was no group differencep-value: <0.05ANOVA
Secondary
Changes From Baseline in Microperimetry (MP) During the Intervention
Microperimetry (MP) was measured by the MP1 Microperimeter
Time frame: at baseline, 24, 48 weeks and 2 years during the intervention
Secondary
Changes From Baseline in Multifocal Electroretinogram (mfERG) at 48 Weeks
Time frame: at baseline and 48 weeks during the intervention
Secondary
Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention
best-spectacle corrected visual acuity (BSCVA) measured by ETDRS chart at baseline and 24 weeks, 48 weeks, 2 years during the intervention. Four participants was excluded during the analysis since they did not finish the intervention. Three did not finish the follow up, while one died from breast cancer.
Time frame: at baseline and 24 weeks, 48 weeks, 2 years during the intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | 2 years | 55.115 letters | Standard Deviation 12.385 |
| Placebo | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | 48 weeks | 53.148 letters | Standard Deviation 10.741 |
| Placebo | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | 24 weeks | 53.444 letters | Standard Deviation 12.509 |
| Placebo | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | baseline | 53.037 letters | Standard Deviation 9.338 |
| Low Lutein | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | 24 weeks | 54.042 letters | Standard Deviation 10.519 |
| Low Lutein | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | baseline | 54.769 letters | Standard Deviation 10.285 |
| Low Lutein | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | 2 years | 56.840 letters | Standard Deviation 7.587 |
| Low Lutein | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | 48 weeks | 56.250 letters | Standard Deviation 10.92 |
| High Lutein | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | 24 weeks | 56.444 letters | Standard Deviation 8.617 |
| High Lutein | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | 48 weeks | 56.846 letters | Standard Deviation 10.035 |
| High Lutein | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | 2 years | 56.074 letters | Standard Deviation 7.77 |
| High Lutein | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | baseline | 54.539 letters | Standard Deviation 8.056 |
| Low Lutein Zeaxanthin | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | baseline | 56.840 letters | Standard Deviation 6.44 |
| Low Lutein Zeaxanthin | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | 48 weeks | 60.875 letters | Standard Deviation 4.919 |
| Low Lutein Zeaxanthin | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | 2 years | 56.600 letters | Standard Deviation 11.839 |
| Low Lutein Zeaxanthin | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | 24 weeks | 56.160 letters | Standard Deviation 14.907 |
| High Zeaxanthin | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | baseline | 56.481 letters | Standard Deviation 7.073 |
| High Zeaxanthin | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | 24 weeks | NA letters | — |
| High Zeaxanthin | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | 48 weeks | 61.600 letters | Standard Deviation 8.093 |
| High Zeaxanthin | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | 2 years | NA letters | — |
| High Lutein Zeaxanthin | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | 2 years | NA letters | — |
| High Lutein Zeaxanthin | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | 48 weeks | 58.500 letters | Standard Deviation 9.437 |
| High Lutein Zeaxanthin | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | 24 weeks | NA letters | — |
| High Lutein Zeaxanthin | Changes of Best-spectacle Corrected Visual Acuity (BSCVA) During the Intervention | baseline | 55.038 letters | Standard Deviation 7.977 |
Comparison: The null hypothesis is no group differencep-value: >0.05ANOVA
Secondary
Changes of Contrast Sensitivity (CSF) Measured by CSV-100 During the Intervention
Time frame: at baseline, 24, 48 weeks and 2 years during the intervention
Secondary
Changes of Flash Recovery Time (FRT) Measured by MDD-2 Macular Adaptometer
Flash recovery time (FRT) was measured by MDD-2 macular adaptometer at baseline, 24, 48 and 96 weeks
Time frame: at baseline, 24, 48 weeks and 2 years during the intervention
Secondary
Changes of Food Pattern From Baseline by Food Frequency Questionnaire During the Intervention
Time frame: at baseline, 24, 48 weeks and 2 years
Secondary
Changes of Serum Xanthophylls Concentrations During the Intervention
Changes of serum xanthophylls concentrations measured by high performance liquid chromatograph (HPLC)at baseline and 4, 12, 24 and 48 weeks during the first 48 weeks of intervention.Four participants was excluded during the analysis since they did not finish the intervention. Three did not finish the follow up, while one died from breast cancer.
Time frame: at baseline and 4, 12, 24 and 48 weeks during the intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Changes of Serum Xanthophylls Concentrations During the Intervention | baseline | 0.330 μmol/L | Standard Deviation 0.404 |
| Placebo | Changes of Serum Xanthophylls Concentrations During the Intervention | 4 weeks | 0.258 μmol/L | Standard Deviation 0.206 |
| Placebo | Changes of Serum Xanthophylls Concentrations During the Intervention | 12 weeks | 0.355 μmol/L | Standard Deviation 0.356 |
| Placebo | Changes of Serum Xanthophylls Concentrations During the Intervention | 24 weeks | 0.281 μmol/L | Standard Deviation 0.261 |
| Placebo | Changes of Serum Xanthophylls Concentrations During the Intervention | 48 weeks | 0.403 μmol/L | Standard Deviation 0.225 |
| Low Lutein | Changes of Serum Xanthophylls Concentrations During the Intervention | 48 weeks | 1.350 μmol/L | Standard Deviation 0.503 |
| Low Lutein | Changes of Serum Xanthophylls Concentrations During the Intervention | baseline | 0.318 μmol/L | Standard Deviation 0.251 |
| Low Lutein | Changes of Serum Xanthophylls Concentrations During the Intervention | 24 weeks | 0.973 μmol/L | Standard Deviation 0.618 |
| Low Lutein | Changes of Serum Xanthophylls Concentrations During the Intervention | 4 weeks | 0.870 μmol/L | Standard Deviation 0.573 |
| Low Lutein | Changes of Serum Xanthophylls Concentrations During the Intervention | 12 weeks | 1.058 μmol/L | Standard Deviation 0.571 |
| High Lutein | Changes of Serum Xanthophylls Concentrations During the Intervention | 12 weeks | 1.450 μmol/L | Standard Deviation 0.93 |
| High Lutein | Changes of Serum Xanthophylls Concentrations During the Intervention | baseline | 0.301 μmol/L | Standard Deviation 0.225 |
| High Lutein | Changes of Serum Xanthophylls Concentrations During the Intervention | 48 weeks | 1.876 μmol/L | Standard Deviation 0.907 |
| High Lutein | Changes of Serum Xanthophylls Concentrations During the Intervention | 4 weeks | 1.041 μmol/L | Standard Deviation 0.661 |
| High Lutein | Changes of Serum Xanthophylls Concentrations During the Intervention | 24 weeks | 1.450 μmol/L | Standard Deviation 0.856 |
| Low Lutein Zeaxanthin | Changes of Serum Xanthophylls Concentrations During the Intervention | 24 weeks | 1.109 μmol/L | Standard Deviation 0.567 |
| Low Lutein Zeaxanthin | Changes of Serum Xanthophylls Concentrations During the Intervention | 4 weeks | 0.965 μmol/L | Standard Deviation 0.711 |
| Low Lutein Zeaxanthin | Changes of Serum Xanthophylls Concentrations During the Intervention | baseline | 0.244 μmol/L | Standard Deviation 0.263 |
| Low Lutein Zeaxanthin | Changes of Serum Xanthophylls Concentrations During the Intervention | 12 weeks | 1.121 μmol/L | Standard Deviation 0.8 |
| Low Lutein Zeaxanthin | Changes of Serum Xanthophylls Concentrations During the Intervention | 48 weeks | 1.136 μmol/L | Standard Deviation 0.542 |
Comparison: The null hypothesis was no group differencep-value: <0.05ANOVA