Macular DegenerationNCT00656903
High Speed Indocyanine Green Angiography Findings in Ranibizumab Treatment for Wet Age-related Macular Degeneration
An observational study of Macular Degeneration, run by National Eye Institute (NEI) at 1 site in United States.
Trial summary
This study will use an eye imaging test called high speed indocyanine green angiography (HS-ICG), which examines leaky vessels in the eye, to try to find out why individuals respond differently to ranibizumab (Lucentis) treatment for wet age-related macular degeneration (AMD). Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Macular Degeneration
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Apr 2008to 19 Aug 2014
- Phase
- Observational
- 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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The participant must understand and sign the IRB-approved informed consent document for the study.
- The participant must be greater than or equal to 50 years old.
- The participant must be diagnosed with AMD in at least one eye defined by the presence of drusen at least 63 (alpha)m in size.
- The participant must have CNV or associated exudation secondary to AMD as determined by the investigator.
- The participant must have visual acuity of better than 20/400 in the affected eye as measured on an ETDRS chart.
- The participant has retinal photographs and angiography of sufficient quality, allowing assessment of the macular area according to standard clinical practice.
- Women participants of childbearing potential must not be pregnant or breast-feeding, must have a negative pregnancy test at screening, must be willing to undergo a urine pregnancy test throughout the study and must practice an adequate method of birth control. Acceptable methods of birth control include hormonal contraception (birth control pills, injected hormones or vaginal ring), intrauterine device, barrier methods with spermicide (diaphragm with spermicide, condom and spermicide) or surgical sterilization (hysterectomy or tubal ligation).
- The participant must be willing and able to comply with the protocol.
Who cannot join
- The participant has CNV, associated with other ocular diseases such as pathologic myopia, ocular histoplasmosis or posterior uveitis, etc.
- The participant has geographic atrophy or fibrosis under the fovea that prevents visual acuity improvement at the discretion of the investigator.
- The participant has decreased vision due to retinal disease not attributable to CNV, such as nonexudative forms of AMD, geographic atrophy, inherited retinal dystrophy, uveitis, or epiretinal membrane.
- The participant has any additional ocular diseases that have irreversibly compromised or could likely compromise the visual acuity of the study eye including amblyopia, anterior ischemic optic neuropathy, clinically significant diabetic macular edema, severe non proliferative diabetic retinopathy, or proliferative diabetic retinopathy.
- The participant has decreased vision due to significant media opacity such as corneal disease or cataract, or opacity precluding photography of the retina; a tear of the RPE; a vitelliform-like lesion of the outer retina (e.g., as in pattern dystrophies or basal laminar cuticular drusen), idiopathic parafoveal telangiectasis, or central serous chorioretinopathy.
- The participant has a history of treatment for CNV in the study eye with focal laser photocoagulation (subfoveal, juxtafoveal or extrafoveal), verteporfin/photodynamic therapy, transpupillary thermotherapy, external beam radiation therapy, or other local treatment (such as submacular surgery) that has resulted in significant subfoveal atrophy or fibrosis as determined by the investigator.
Show all 21Show fewer
- The participant has had previous ranibizumab, bevacizumab or pegaptanib sodium treatments in the study eye less than four weeks prior to enrollment.
- The participant has had prior verteporfin/photodynamic therapy in the fellow eye less than one week prior to enrollment.
- The participant has evidence of ocular toxoplasmosis; external ocular infection, including conjunctivitis; chalazion; significant blepharitis; or aphakia in the study eye.
- The participant has a history of systemic anti-VEGF therapy less than four weeks prior to enrollment.
- The participant has had intraocular surgery (including lens replacement surgery) within six weeks prior to enrollment.
- The participant has a history of (within the last six months), or current ocular or periocular infection (including any history of ocular herpes zoster or simplex).
- The participant has had a prior vitrectomy in the study eye.
- The participant has medical problems that make consistent follow-up over the treatment period unlikely (e.g., stroke, severe MI, end stage malignancy), any contraindications to performing the necessary diagnostic studies (i.e., known allergy to indocyanine green or fluorescein dyes, etc.), or in general is a poor medical risk because of other systemic diseases or active uncontrolled infections.
- The participant has had insertion of a sclera buckle in the study eye.
- The participant has clinical evidence of scleral thinning (defined as an area of blue/grey discoloration of the sclera representing visualization of underlying choroidal tissue through a thinned area of sclera) seen at the time of external eye examination.
- The participant exhibits clinical signs of myopic retinopathy, or has a refraction of > spherical equivalent 8.00D in their current prescription. Pseudophakic participants may be enrolled in this study if there is no funduscopic evidence of degenerative myopia present and if there is no medical history prior to the participants cataract surgery of either myopic retinopathy or a refraction of > spherical equivalent 8.00D.
- The participant has a history of a corneal transplant.
- The participant has infectious conjunctivitis, keratitis, scleritis, or endophthalmitis.
- The participant is currently undergoing treatment for active ocular infection.
- The participant has a shellfish allergy, iodine allergy or liver disease.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: High Speed Indocyanine Green Angiography Findings in Induction/PRN Regimen of Intravitreal Ranibizumab Injection for Neovascular Age-Related Macular Degeneration
This study will use an eye imaging test called high speed indocyanine green angiography (HS-ICG), which examines leaky vessels in the eye, to try to find out why individuals respond differently to ranibizumab (Lucentis) treatment for wet age-related macular degeneration (AMD). The drug was recently approved by the Food and Drug Administration to treat this disease, but the response to the treatment varies markedly among individuals.
People 50 years of age and older with wet AMD and vision that meets the research protocol criteria may be eligible for this study. Participants undergo the following procedures:
Read more
Ranibizumab injections in the study eye once a month for 4 months. Additional injections are given only if the study eye shows signs of bleeding or leaking fluid. The eye is numbed before the injection and the eye area is cleaned with an antiseptic. Antibiotic drops are used for 3 days following the injection to prevent infection.
Clinic visits once a month for 2 years for evaluations to monitor the response to treatment. The evaluations may include the following examinations and tests:
- Eye examination with dilation, optical coherence tomography and photography: The examination measures visual acuity, thickness of your retina (the back of the eye) andeye pressure. Bright lights will also be used so that the doctor can see the back of your eye. Photographs of the eye may be taken.
- Fluorescein angiography to examine the blood vessels in the eye: A dye called fluorescein is injected into a vein in the arm. The dye travels through the veins to the blood vessels in the eyes. A camera takes pictures of the dye as it flows through the blood vessels. This test is done eight times during the study.
- Indocyanine green angiography to examine the blood vessels in the eye: The procedure is the same as for fluorescein angiography, but it uses a dye called indocyanine green. This test is done once a month for the first year of the study and then every 3 months.
Read the detailed description
Neovascular age-related macular degeneration (AMD) is the leading cause of blindness among elderly in the United States.1 Ranibizumab, an inhibitor of all forms of vascular endothelial growth factor (VEGF), is the first FDA-approved treatment for AMD that significantly improves vision in a quarter to a third of patients and maintains or improves vision in greater than 90% of patients. Ranibizumab decreases the vasopermeability as measured by decreased leakage and fluid on fluorescein (FA) and optical coherence tomography. However, the effect of ranibizumab on the structure and hemodynamics of the choroidal neovascularization (CNV) in AMD, as measured with high-speed indocyanine green angiography (HS-ICG), is not known. The effect or lack of effect on the physical structure of the CNV may help explain the variability of injection frequencies and visual responses among different patients. Since anti-VEGF therapy is designed to inhibit exudative CNV, it is clinically important to develop a standard reproducible method to assess HS-ICG.
In this observational study, our primary objective is to assess whether induction/pro re nata (Induction/PRN) 0.5 mg intravitreal ranibizumab-based treatment for neovascular AMD decreases the size and pattern of the CNV as measured on HS-ICG, as opposed to simply decreasing leakage and fluid as seen on FA and OCT. Although combination therapy is likely the standard treatment for AMD in the future, participants will not be allowed to receive other AMD experimental agents (e.g., immunosuppressive drugs) for either the study or fellow eye while on this study. In consultation with various reading centers, we will attempt to develop a reproducible schema for evaluation of HS-ICG by reviewing pre-treatment and post-treatment HS-ICGs. The grading system development is a secondary objective to achieve a better understanding of anatomical and functional results and an important task for future research. In this study, the first 10 cases will be used to attempt to develop a reproducible grading system. The NEI retina group will review these ICGs and attempt to identify gradable aspects of the lesions that are consistently present on the ICGs. During this time we will continue to collect additional cases for evaluation. The grading system proposed from the first 10 cases will be implemented in the next 10 cases. There will be two independent gradings for each ICG. The results of this dual grading will then be reviewed and problematic areas of grading will be identified. The grading system will be modified based on this experience and reproducibility of the modified grading system will be assessed by re-grading the images in a masked fashion. The modified grading system will be utilized in the next 10 cases. This iterative process will be continued until we have either developed a reproducible and useful grading system or completed the full participant analysis. Another important secondary objective is to examine whether an increased dose of 1 mg of intravitreal ranibizumab-based treatment (administered as 1 mg monthly or 0.5 mg bi-monthly) will decrease leakage and fluid as seen on FA and OCT and/or decrease the size and pattern of CNV on HS-ICG for participants not becoming fluid-free on the standard dose.
- Conditions
- Macular Degeneration
- Keywords
- Lucentis, Indocyanine Green Angiography, Choroidal Neovascularization, Macular Degeneration, Ranibizumab, Age-Related Macular Degeneration, AMD
- Medical subject headings
- Macular Degeneration, Choroidal Neovascularization
What is being measured
The primary outcome is the main question the study is designed to answer.
To develop a grading system that can be used to assess the effects of (Induction/PRN) ranibizumab therapy on reducing the neovascular membrane associated with AMD as seen on HS-ICG
Secondary outcomes (1)
Changes in vision; lesion size measured with HS-ICG and FA; leakage measured with FA; changes in retinal thickening measured with OCT; and the safety and tolerability of ranibizumab
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2008 (estimated)
- Study start7 Apr 2008
- Study completion19 Aug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Macular DegenerationStudies 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
- Observational
- Time perspective
- Prospective
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Eye Institute (NEI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Henry E Wiley, M.D., Principal investigator, National Eye Institute (NEI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00656903
- Sponsor's protocol ID
- 080103
- Other IDs
- 08-EI-0103
- Status last verified
- 19 Aug 2014
- First submitted
- 10 Apr 2008
- Last updated
- 4 Dec 2019
- Results posted
- No
Publications
Bressler NM, Bressler SB, Fine SL. Age-related macular degeneration. Surv Ophthalmol. 1988 May-Jun;32(6):375-413. doi: 10.1016/0039-6257(88)90052-5.
PubMed 2457955Laser photocoagulation of subfoveal neovascular lesions in age-related macular degeneration. Results of a randomized clinical trial. Macular Photocoagulation Study Group. Arch Ophthalmol. 1991 Sep;109(9):1220-31. doi: 10.1001/archopht.1991.01080090044025.
PubMed 1718250Pieramici DJ, Avery RL. Ranibizumab: treatment in patients with neovascular age-related macular degeneration. Expert Opin Biol Ther. 2006 Nov;6(11):1237-45. doi: 10.1517/14712598.6.11.1237.
PubMed 17049020
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High Speed Indocyanine Green Angiography Findings in Induction/PRN Regimen of Intravitreal Ranibizumab Injection for Neovascular Age-Related Macular Degeneration
- ClinicalTrials.gov ID
- NCT00656903
- Acronym / sponsor ID
- 080103
- Conditions
- Macular Degeneration
- Keywords
- Lucentis, Indocyanine Green Angiography, Choroidal Neovascularization, Macular Degeneration, Ranibizumab, Age-Related Macular Degeneration, AMD
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- National Eye Institute (NEI)US National Institutes of Health
- Study start
- 7 Apr 2008
- Study completion
- 19 Aug 2014
- First posted
- 11 Apr 2008 (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.
This study will use an eye imaging test called high speed indocyanine green angiography (HS-ICG), which examines leaky vessels in the eye, to try to find out why individuals respond differently to ranibizumab (Lucentis) treatment for wet age-related macular degeneration (AMD). The drug was recently approved by the Food and Drug Administration to treat this disease, but the response to the treatment varies markedly among individuals.
People 50 years of age and older with wet AMD and vision that meets the research protocol criteria may be eligible for this study. Participants undergo the following procedures:
Ranibizumab injections in the study eye once a month for 4 months. Additional injections are given only if the study eye shows signs of bleeding or leaking fluid. The eye is numbed before the injection and the eye area is cleaned with an antiseptic. Antibiotic drops are used for 3 days following the injection to prevent infection.
Clinic visits once a month for 2 years for evaluations to monitor the response to treatment. The evaluations may include the following examinations and tests:
- Eye examination with dilation, optical coherence tomography and photography: The examination measures visual acuity, thickness of your retina (the back of the eye) andeye pressure. Bright lights will also be used so that the doctor can see the back of your eye. Photographs of the eye may be taken.
- Fluorescein angiography to examine the blood vessels in the eye: A dye called fluorescein is injected into a vein in the arm. The dye travels through the veins to the blood vessels in the eyes. A camera takes pictures of the dye as it flows through the blood vessels. This test is done eight times during the study.
- Indocyanine green angiography to examine the blood vessels in the eye: The procedure is the same as for fluorescein angiography, but it uses a dye called indocyanine green. This test is done once a month for the first year of the study and then every 3 months.
Detailed description
Neovascular age-related macular degeneration (AMD) is the leading cause of blindness among elderly in the United States.1 Ranibizumab, an inhibitor of all forms of vascular endothelial growth factor (VEGF), is the first FDA-approved treatment for AMD that significantly improves vision in a quarter to a third of patients and maintains or improves vision in greater than 90% of patients. Ranibizumab decreases the vasopermeability as measured by decreased leakage and fluid on fluorescein (FA) and optical coherence tomography. However, the effect of ranibizumab on the structure and hemodynamics of the choroidal neovascularization (CNV) in AMD, as measured with high-speed indocyanine green angiography (HS-ICG), is not known. The effect or lack of effect on the physical structure of the CNV may help explain the variability of injection frequencies and visual responses among different patients. Since anti-VEGF therapy is designed to inhibit exudative CNV, it is clinically important to develop a standard reproducible method to assess HS-ICG.
In this observational study, our primary objective is to assess whether induction/pro re nata (Induction/PRN) 0.5 mg intravitreal ranibizumab-based treatment for neovascular AMD decreases the size and pattern of the CNV as measured on HS-ICG, as opposed to simply decreasing leakage and fluid as seen on FA and OCT. Although combination therapy is likely the standard treatment for AMD in the future, participants will not be allowed to receive other AMD experimental agents (e.g., immunosuppressive drugs) for either the study or fellow eye while on this study. In consultation with various reading centers, we will attempt to develop a reproducible schema for evaluation of HS-ICG by reviewing pre-treatment and post-treatment HS-ICGs. The grading system development is a secondary objective to achieve a better understanding of anatomical and functional results and an important task for future research. In this study, the first 10 cases will be used to attempt to develop a reproducible grading system. The NEI retina group will review these ICGs and attempt to identify gradable aspects of the lesions that are consistently present on the ICGs. During this time we will continue to collect additional cases for evaluation. The grading system proposed from the first 10 cases will be implemented in the next 10 cases. There will be two independent gradings for each ICG. The results of this dual grading will then be reviewed and problematic areas of grading will be identified. The grading system will be modified based on this experience and reproducibility of the modified grading system will be assessed by re-grading the images in a masked fashion. The modified grading system will be utilized in the next 10 cases. This iterative process will be continued until we have either developed a reproducible and useful grading system or completed the full participant analysis. Another important secondary objective is to examine whether an increased dose of 1 mg of intravitreal ranibizumab-based treatment (administered as 1 mg monthly or 0.5 mg bi-monthly) will decrease leakage and fluid as seen on FA and OCT and/or decrease the size and pattern of CNV on HS-ICG for participants not becoming fluid-free on the standard dose.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- The participant must understand and sign the IRB-approved informed consent document for the study.
- The participant must be greater than or equal to 50 years old.
- The participant must be diagnosed with AMD in at least one eye defined by the presence of drusen at least 63 (alpha)m in size.
- The participant must have CNV or associated exudation secondary to AMD as determined by the investigator.
- The participant must have visual acuity of better than 20/400 in the affected eye as measured on an ETDRS chart.
Key exclusion criteria (21 listed)
- The participant has CNV, associated with other ocular diseases such as pathologic myopia, ocular histoplasmosis or posterior uveitis, etc.
- The participant has geographic atrophy or fibrosis under the fovea that prevents visual acuity improvement at the discretion of the investigator.
- The participant has decreased vision due to retinal disease not attributable to CNV, such as nonexudative forms of AMD, geographic atrophy, inherited retinal dystrophy, uveitis, or epiretinal membrane.
- The participant has any additional ocular diseases that have irreversibly compromised or could likely compromise the visual acuity of the study eye including amblyopia, anterior ischemic optic neuropathy, clinically significant diabetic macular edema, severe non proliferative diabetic retinopathy, or proliferative diabetic retinopathy.
- The participant has decreased vision due to significant media opacity such as corneal disease or cataract, or opacity precluding photography of the retina; a tear of the RPE; a vitelliform-like lesion of the outer retina (e.g., as in pattern dystrophies or basal laminar cuticular drusen), idiopathic parafoveal telangiectasis, or central serous chorioretinopathy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To develop a grading system that can be used to assess the effects of (Induction/PRN) ranibizumab therapy on reducing the neovascular membrane associated with AMD as seen on HS-ICG
1 secondary outcome
Changes in vision; lesion size measured with HS-ICG and FA; leakage measured with FA; changes in retinal thickening measured with OCT; and the safety and tolerability of ranibizumab
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 4 Dec 2019.
- Background: PubMed 2457955Bressler NM, Bressler SB, Fine SL. Age-related macular degeneration. Surv Ophthalmol. 1988 May-Jun;32(6):375-413. doi: 10.1016/0039-6257(88)90052-5.
- Background: PubMed 1718250Laser photocoagulation of subfoveal neovascular lesions in age-related macular degeneration. Results of a randomized clinical trial. Macular Photocoagulation Study Group. Arch Ophthalmol. 1991 Sep;109(9):1220-31. doi: 10.1001/archopht.1991.01080090044025.
- Background: PubMed 17049020Pieramici DJ, Avery RL. Ranibizumab: treatment in patients with neovascular age-related macular degeneration. Expert Opin Biol Ther. 2006 Nov;6(11):1237-45. doi: 10.1517/14712598.6.11.1237.
Related trials for Macular Degeneration
RecruitingPhase 3
A Study of 36-Week Refill Exchanges of Port Delivery System (PDS) With Ranibizumab in nAMD
Neovascular Age-related Macular Degeneration
RecruitingObservational study
Pivotal Trial of an Automated AI-based System for Early Diagnosis and Prediction of Late Age-related Macular Degeneration
Age-related Macular Degeneration (AMD)
Active, not recruitingObservational study
Real World Evidence in China: Faricimab Use in Diabetic Macular Edema, Retinal Vein Occlusion, and Neovascular Age-Related Macular Degeneration (The Farseeing Study)
Diabetic Macular Edema, Neovascular Age-related Macular Degeneration
Active, not recruitingObservational study
Retinal Pigment Epithelium Safety Study For Patients In B4711001
Age Related Macular Degeneration
RecruitingObservational study
National Ophthalmic Genotyping and Phenotyping Network (eyeGENE (Registered Trademark)), Stage 3 - Expansion of DNA and Data Repositories for Rare Inherited Ophthalmic Diseases
Inherited Ophthalmic Diseases, Hypopigmentation Disorder
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.
Henry E Wiley, M.D. principal investigator
National Eye Institute (NEI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Macular Degeneration, run by National Eye Institute (NEI) 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 8 inclusion and 21 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 4 Dec 2019. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
To develop a grading system that can be used to assess the effects of (Induction/PRN) ranibizumab therapy on reducing the neovascular membrane associated with AMD as seen on HS-ICG. 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 NCT00656903, which also lists 3 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 4 Dec 2019.