Age Related Macular DegenerationNCT01363570
Evaluation of Wet Age-Related Macular Degeneration (AMD) Genetic Profile Interactions With Ranibizumab Treatment Outcomes
A study testing Ranibizumab in people with Age Related Macular Degeneration, run by McMaster University at 2 sites in Canada.
Trial summary
Age Related Macular Degeneration (AMD) is the leading cause of blindness in North America. This condition causes a progressive loss of central vision, the part of your vision that allows you to read, drive and see images in sharp detail directly in front of you. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Age Related Macular Degeneration
- What is being tested?
- Ranibizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 2 sitesCanada
- Study dates
- Jan 2012to Oct 2014
- Phase
- Interventional
- 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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must be at least 18 years of age
- Choroidal neovascularization (CNV) secondary to age-related macular degeneration
- CNV under geometric center of the foveal avascular zone
- Evidence of activity on fundus fluorescein angiography
- Evidence of CNV activity as suggested by one of the following: sub-retinal hemorrhage, sub-retinal lipid, documented loss of 3 lines of vision within the last 3 months
- Visual acuity of between 20/40 and 20/300 in the study eye tested via Early treatment of Diabetic Retinopathy Study (ETDRS) eye chart score of 34 to 73 letters at 2 meters.
Who cannot join
- Individuals with choroidal neovascularization from causes other than AMD
- Patients physically unable to tolerate intravenous fluorescein angiography
- Patients with medically uncontrolled glaucoma
- Any intraocular surgery within 3 months in the study eye
- Prior retinal or vitreous surgery including vitrectomy or scleral buckling
- Any significant ocular disease other than AMD that has compromised or could compromise vision in the study eye and confound analysis of the primary outcome
- Individuals with physical or mental disabilities that prevent accurate vision testing
- History of any laser treatment of CNV in study eye (laser photocoagulation or prior photodynamic therapy), or anti-VEGF (ranibizumab or bevacizumab) in the past 6 months in the study eye.
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
St. Joseph's Healthcare Hamilton Regional Eye Centre
Hamilton, Ontario, L8G 5E4
Toronto Western Hospital Eye Clinic
Toronto, Ontario, M5T 2S8
About this study
Age Related Macular Degeneration (AMD) is the leading cause of blindness in North America. This condition causes a progressive loss of central vision, the part of your vision that allows you to read, drive and see images in sharp detail directly in front of you. The wet form of AMD is characterized by the growth and leakage of small blood vessels into the choroid layer of the eye, or the back of the eye. These leaking blood vessels disrupt the structure and function of the eye, causing loss of vision, particularly the sharp vision created by the macula area of the eye.
Currently, the best treatment for wet AMD is a series of injections of an anti-vascular endothelial growth factor (anti-VEGF) drug, ranibizumab (Lucentis). The clinical response to treatment is varied. Approximately 70% of patients see a moderate vision gain (3-line gain on a visual acuity chart), but there are 30% who do not see a similar improvement in vision. There is no way to identify those patients who will respond with significant vision gain versus those who will not experience moderate vision gain. Recent research into AMD has demonstrated that genetic mutations are proving to be key risk factors for patients developing wet AMD, with up to 80% of wet AMD cases explained by inherited genetic variations. Scientists have theorized that there may be a genetic difference between those patients who see significant responses to treatment and those who do not. The investigators will be testing participant's genetic profile using the Macula Risk test and following their progress through the standard treatment for wet AMD over the course of this study. This study aims to demonstrate the association between known genetic variations and patient responses to treatment.
Read the detailed description
Your ophthalmologist will determine your suitability for this study through a screening protocol. You will have measurements of your visual acuity and will undergo a series of imaging tests as described in the next paragraph to show presence of blood vessel growth in the back of your eye (the choroid). You cannot be included in this study if you have another significant eye disease that affects your vision, if you have blood vessel growth in the back of your eye (choroid) for reasons other than AMD, if you have medically uncontrolled glaucoma, if you have been treated for AMD in that past, if you have had intra-ocular surgery in the study eye in the past 3 months, if you have had any past retinal or vitreous surgery, or if you have physical or mental disabilities that would prevent accurate vision testing.
At the beginning of the study, we will take a sample of cells from the inside of your cheek, using a small swab. The sample will be sent to a genetic laboratory for analysis and storage. This information will be kept masked for the duration of the study, meaning that you, the study ophthalmologist and the data analyzer will not know the results of the genetic test until the study is completed.
You will be asked to come in for an initial assessment to determine your starting visual abilities and medical history. On your next appointment, you will receive your first treatment of intra-vitreal injections of Ranibizumab (Lucentis). You will be asked to come into the clinic every month for six (6) months total for treatment injections and testing. At each appointment, we will take 3-D images of your retina (the back of your eye) using an Optical Coherence Tomography (OCT) imaging device, test your eye pressure and determine if there are any signs of infection or inflammation from the injections. On months 1, 3, and 6 we will also test your vision, your contrast sensitivity using a standard contrast sensitivity chart (The Pelli-Robson chart) and take images of the blood vessel growth using a coloured dye (fluorescein) to help us see your vessels. Before every treatment, anesthetic eye drops (proparacaine) will be applied to your eye so you will not feel the injections. You will be given antibiotic eye drops (Zymar®) that you will be asked to use 4 times a day for a few days after the injection to prevent infection.
- Conditions
- Age Related Macular Degeneration
- Being tested
- Ranibizumab
- Keywords
- Macular Degeneration, Age related macular degeneration, Macula Risk, Genetic test, Anti-inflammatory, Anti-vascular endothelial growth factor (Anti-VEGF), Lucentis, Ranibizumab, Vision loss
- Medical subject headings
- Macular Degeneration, Vision Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RanibizumabDrug
Also called Lucentis
Intra-vitreal injections of 0.5mg/0.05 mL dosage, injected at months 0, 1, and 2. For those requiring additional injections, patients will receive monthly treatment up to a maximum of 6 months total.
| Study group | Role | What they receive |
|---|---|---|
| Ranibizumab | Other | Ranibizumab is the current gold standard treatment for wet age-related macular degeneration. This intervention is approved by Health Canada, covered by OHIP (Ontario Health Insurance Plan) and used regularly by ophthalmologists in Canada. Participants will receive intravitreal injections of ranibizumab each month for up to 6 months, with ocular testing at each appointment as prescribed by the study protocol. Receives: Drug: Ranibizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gains in visual acuity
Percent probability gains in visual acuity will be assessed by comparing best corrected visual acuity at each follow up appointment by the standardized vision testing, early treatment diabetic retinopathy study (ETDRS) test. The ETDRS visual acuity test was first developed to effectively evaluate visual changes following panretinal photocoagulation in patients with diabetic retinopathy. This method of measuring visual acuity was more accurate than previous methods, and thus has become the global standard, especially for clinical trials where it is essential to have utmost accuracy.
Measured: Baseline and months 1, 2, 3, 4, 5, and 6
Secondary outcomes (6)
Changes in choroid vessel activity in lesion growth and activity at choroid
The changes in blood vessel lesion growth and activity will be measured by OCT (Ocular Coherence Tomography) and fundus fluoroscein angiography to assess choroidal neovascular leakage
Measured: Baseline and months 1, 2, 3, 4, 5 and 6
Rate of cataract progression
Measured at each appointment with a slit lamp examination
Measured: Baseline and months 1, 2, 3, 4, 5, and 6
Resolution of macular edema
The speed at which macular edema resolves will be visually measured using optical coherence tomography
Measured: Baseline and months 1, 2, 3, 4, 5, 6
Mean change in visual acuity according to identified genetic mutations
Mean change in visual acuity according to individual mutations at the CFH haplotypes/C3 rs2230199 marker/ARMS2 rs10490924 marker and mt A4917G marker, calculated using the Macula Risk findings and visual acuity results as determined using ETDRS visual screening
Measured: Baseline and Months 1, 2, 3, 4, 5, 6
Mean change in visual acuity regardless of genetic profile results
Measured: Baseline and Months 1, 2, 3, 4, 5, 6
Interaction of smoking status and genetic profile on visual acuity changes
Measured: Baseline and Months 1, 2, 3, 4, 5, 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2011 (estimated)
- Study startJan 2012
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Age Related Macular DegenerationStudies of the same condition, open and under way.
- More trials run by McMaster UniversityThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian National Institute for the Blind
- Responsible party
- Sponsor
- Investigators
- Varun Chaudhary, MD, FRCSC, Principal investigator, St. Joseph's Healthcare Hamilton/McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01363570
- Sponsor's protocol ID
- AMDgene12011
- Status last verified
- Mar 2016
- First submitted
- 30 May 2011
- Last updated
- 17 Mar 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Wet Age-Related Macular Degeneration (AMD) Genetic Profile Interactions With Ranibizumab Treatment Outcomes
- ClinicalTrials.gov ID
- NCT01363570
- Acronym / sponsor ID
- AMDgene12011
- Conditions
- Age Related Macular Degeneration
- Keywords
- Macular Degeneration, Age related macular degeneration, Macula Risk, Genetic test, Anti-inflammatory, Anti-vascular endothelial growth factor (Anti-VEGF), Lucentis, Ranibizumab
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Collaborators
- Canadian National Institute for the Blind
- Study start
- Jan 2012
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 1 Jun 2011 (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.
Age Related Macular Degeneration (AMD) is the leading cause of blindness in North America. This condition causes a progressive loss of central vision, the part of your vision that allows you to read, drive and see images in sharp detail directly in front of you. The wet form of AMD is characterized by the growth and leakage of small blood vessels into the choroid layer of the eye, or the back of the eye. These leaking blood vessels disrupt the structure and function of the eye, causing loss of vision, particularly the sharp vision created by the macula area of the eye.
Currently, the best treatment for wet AMD is a series of injections of an anti-vascular endothelial growth factor (anti-VEGF) drug, ranibizumab (Lucentis). The clinical response to treatment is varied. Approximately 70% of patients see a moderate vision gain (3-line gain on a visual acuity chart), but there are 30% who do not see a similar improvement in vision. There is no way to identify those patients who will respond with significant vision gain versus those who will not experience moderate vision gain. Recent research into AMD has demonstrated that genetic mutations are proving to be key risk factors for patients developing wet AMD, with up to 80% of wet AMD cases explained by inherited genetic variations. Scientists have theorized that there may be a genetic difference between those patients who see significant responses to treatment and those who do not. The investigators will be testing participant's genetic profile using the Macula Risk test and following their progress through the standard treatment for wet AMD over the course of this study. This study aims to demonstrate the association between known genetic variations and patient responses to treatment.
Detailed description
Your ophthalmologist will determine your suitability for this study through a screening protocol. You will have measurements of your visual acuity and will undergo a series of imaging tests as described in the next paragraph to show presence of blood vessel growth in the back of your eye (the choroid). You cannot be included in this study if you have another significant eye disease that affects your vision, if you have blood vessel growth in the back of your eye (choroid) for reasons other than AMD, if you have medically uncontrolled glaucoma, if you have been treated for AMD in that past, if you have had intra-ocular surgery in the study eye in the past 3 months, if you have had any past retinal or vitreous surgery, or if you have physical or mental disabilities that would prevent accurate vision testing.
At the beginning of the study, we will take a sample of cells from the inside of your cheek, using a small swab. The sample will be sent to a genetic laboratory for analysis and storage. This information will be kept masked for the duration of the study, meaning that you, the study ophthalmologist and the data analyzer will not know the results of the genetic test until the study is completed.
You will be asked to come in for an initial assessment to determine your starting visual abilities and medical history. On your next appointment, you will receive your first treatment of intra-vitreal injections of Ranibizumab (Lucentis). You will be asked to come into the clinic every month for six (6) months total for treatment injections and testing. At each appointment, we will take 3-D images of your retina (the back of your eye) using an Optical Coherence Tomography (OCT) imaging device, test your eye pressure and determine if there are any signs of infection or inflammation from the injections. On months 1, 3, and 6 we will also test your vision, your contrast sensitivity using a standard contrast sensitivity chart (The Pelli-Robson chart) and take images of the blood vessel growth using a coloured dye (fluorescein) to help us see your vessels. Before every treatment, anesthetic eye drops (proparacaine) will be applied to your eye so you will not feel the injections. You will be given antibiotic eye drops (Zymar®) that you will be asked to use 4 times a day for a few days after the injection to prevent infection.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ranibizumab | Other | Drug: RanibizumabRanibizumab is the current gold standard treatment for wet age-related macular degeneration. This intervention is approved by Health Canada, covered by OHIP (Ontario Health Insurance Plan) and used regularly by ophthalmologists in Canada. Participants will receive intravitreal injections of ranibizumab each month for up to 6 months, with ocular testing at each appointment as prescribed by the study protocol. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients must be at least 18 years of age
- Choroidal neovascularization (CNV) secondary to age-related macular degeneration
- CNV under geometric center of the foveal avascular zone
- Evidence of activity on fundus fluorescein angiography
- Evidence of CNV activity as suggested by one of the following: sub-retinal hemorrhage, sub-retinal lipid, documented loss of 3 lines of vision within the last 3 months
Key exclusion criteria (8 listed)
- Individuals with choroidal neovascularization from causes other than AMD
- Patients physically unable to tolerate intravenous fluorescein angiography
- Patients with medically uncontrolled glaucoma
- Any intraocular surgery within 3 months in the study eye
- Prior retinal or vitreous surgery including vitrectomy or scleral buckling
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 |
|---|---|---|
| RanibizumabAlso: LucentisIntra-vitreal injections of 0.5mg/0.05 mL dosage, injected at months 0, 1, and 2. For those requiring additional injections, patients will receive monthly treatment up to a maximum of 6 months total. | Drug | Ranibizumab |
Primary outcome
Gains in visual acuity
Time frame: Baseline and months 1, 2, 3, 4, 5, and 6
Percent probability gains in visual acuity will be assessed by comparing best corrected visual acuity at each follow up appointment by the standardized vision testing, early treatment diabetic retinopathy study (ETDRS) test. The ETDRS visual acuity test was first developed to effectively evaluate visual changes following panretinal photocoagulation in patients with diabetic retinopathy. This method of measuring visual acuity was more accurate than previous methods, and thus has become the global standard, especially for clinical trials where it is essential to have utmost accuracy.
6 secondary outcomes
Changes in choroid vessel activity in lesion growth and activity at choroid
Time frame: Baseline and months 1, 2, 3, 4, 5 and 6
Rate of cataract progression
Time frame: Baseline and months 1, 2, 3, 4, 5, and 6
Resolution of macular edema
Time frame: Baseline and months 1, 2, 3, 4, 5, 6
Mean change in visual acuity according to identified genetic mutations
Time frame: Baseline and Months 1, 2, 3, 4, 5, 6
Mean change in visual acuity regardless of genetic profile results
Time frame: Baseline and Months 1, 2, 3, 4, 5, 6
Interaction of smoking status and genetic profile on visual acuity changes
Time frame: Baseline and Months 1, 2, 3, 4, 5, 6
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 17 Mar 2016.
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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.
Varun Chaudhary, MD, FRCSC principal investigator
St. Joseph's Healthcare Hamilton/McMaster University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ranibizumab in people with Age Related Macular Degeneration, run by McMaster University at 2 sites in Canada.
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 8 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 17 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. 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?
Gains in visual acuity (time frame: Baseline and months 1, 2, 3, 4, 5, and 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Mar 2016.