Retinal Artery OcclusionPhase 2NCT03090087
The Effect of A2A Adrenoceptor Stimulation on the Diameter of Retinal Arterioles During Hypoxia in Vivo
A Phase 2 study testing Hypoxia and Regadenoson in people with Retinal Artery Occlusion, run by University of Aarhus at 1 site in Denmark.
Trial summary
The purpose is to investigate how the adenosine affects the diameter regulation of retinal arterioles during changes in oxygen tension. A deeper understanding of the mechanisms involved in diameter regulation of retinal arterioles during changes in oxygen tension can be used to obtain a more detailed understanding of… Read more about this study
- Who is it for?
- Ages 20 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Retinal Artery Occlusion
- What is being tested?
- Hypoxia and Regadenoson
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteDenmark
- Study dates
- 22 Mar 2017to Nov 2017
- Phase
- Phase 2
- 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 20 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age 20-35
- Healthy, both current and prior
- Normal echocardiogram
- Signed and informed consent
Who cannot join
- Former or current cardiovascular disease or high blood pressure
- Lung diseases incl. asthma or chronic obstructive pulmonary disease (COPD)
- Known eye disease or previously treated for an eye disease, particularly glaucoma and cataracts
- People taking medication, except birth control pills
- Persons who have or who have had epilepsy
- Pregnant or breast-feeding women
- Allergies to the constituent substance of the medication used in the study
Trial locations and contacts
1 site in 1 country.
Denmark1 site, 1 recruiting
- Recruiting
Department of Ophthalmology, Aarhus University Hospital
Aarhus, 8000
Anna Dons-Jensen, Student, +45 78463250, annadonsjensen@gmail.com
Line Petersen, Ph.D., +45 78463250, linperse@rm.dk
About this study
The purpose is to investigate how the adenosine affects the diameter regulation of retinal arterioles during changes in oxygen tension. A deeper understanding of the mechanisms involved in diameter regulation of retinal arterioles during changes in oxygen tension can be used to obtain a more detailed understanding of diseases where changes in the diameter regulation of retinal vessels are involved in the disease pathogenesis and possibly point to new therapeutic options for patients with retinal vascular disease, such as diabetic retinopathy and retinal vein thrombosis.
Preliminary, a routine ophthalmological evaluation, measurement of blood pressure, and electrocardiogram will be preformed to insure that only healthy test persons are included in the study.
Read more
The test persons will be randomly allocated to two groups, one group in which protocol 1 is followed by protocol 2, and the other group with the two protocols performed in the reverse order.
Protocol 1: Using the DVA, a video recording will capture the diameter of retinal vessels and the changes occurring during stimulation with flickering light. The recording lasts 4.5 minutes and is preformed before and after intravenous injection of adenosine.
Protocol 2: The procedures are similar to those of protocol 1 but are performed during breathing of a gas mixture with a reduced oxygen tension to 12,5 %, which results in a reduced oxygen saturation in the blood to 85-90 %.
Read the detailed description
Background:
Occlusion of the retinal vessels leading to retinal ischaemia and hypoxia is an important element in the pathophysiology of the major vision threatening diseases in the Western World. The hypoxic areas release vasodilating factors that induce vasodilatation in adjacent retinal areas in order to increase blood flow and retinal oxygenation. An understanding of the mechanisms underlying this vasodilatation may help identifying new therapeutic principles for modulating retinal blood flow during changes in retinal blood flow secondary to hypoxia and other diseases.
The present study:
Two working hypotheses will be tested: 1) That systemic administration of an A2A adrenoceptor agonist affects retinal blood flow independently of its systemic effects. 2) That the vasodilating effect of A2A adrenoceptor stimulation and the vasodilating effects of systemic hypoxia and increased retinal metabolism induced by flicker stimulation are additive.
Methods:
The diameter of retinal vessels are measured using the Dynamic Vessel Analyser (DVA). This apparatus performs video recordings of the ocular fundus, and the single images in the video sequences are grabbed for computerised analysis. Special software enables calculation of the diameter of the vessel on the basis of the distance between the vessel borders. The fact that images are grabbed real time (25 times per second) allows the detection of immediate diameter changes when the retinal metabolism is increased by exposure to flickering light (metabolic autoregulation).
The A2A adrenoceptor agonist regadenoson is administered during continuous ECG monitoring as a single intravenous injection of 400 micrograms (5 ml) in an antecubital vein. No dose adjustments are necessary for body weight, age, renal og hepatic impairment. Due to a potential ischaemic effect of regadenoson, only persons with no history of arterial hypertension or cardiac disease and with normal blood pressure and ECG will be included.
The experiments will be performed during breathing of ambient air and after 10 minutes of breathing air containing 12.5% oxygen (corresponding to the saturation at an altitude of 4100 m), which induces a decline in the arterial oxygen saturation resulting in dilatation of retinal vessels.
Experimental design:
The project will be conducted as an open controlled interventional study performed on two days separated by at least one day. Initial a routine ophthalmological evaluation with a slit lamp examination, measurement of the intraocular pressure and ophthalmoscopy, supplemented with a measurement of central retinal thickness using optical coherence tomography scanning will be preformed as will measuring of ECG and blood pressure to make sure only healthy test persons are included.
The test persons will be randomly allocated to two groups, one group in which protocol 1 is followed by protocol 2, and the other group with the two protocols performed in the reverse order.
Protocol 1:
- Using the DVA, the diameter of a larger retinal vascular arcade arteriole will be recorded for 90 seconds at baseline followed by a similar recording during stimulation with flickering light and a recording during rest, altogether lasting 4.5 minutes B) Intravenous injection of 0,4 mg regadenoson and repetition of the procedures in step A
Protocol 2:
The procedures are similar to those of protocol 1 but are performed during breathing of a hypoxic gas mixture.
- Conditions
- Retinal Artery Occlusion
- Being tested
- Hypoxia, Regadenoson
- Keywords
- Diameter of retinal arteries, Adenosine, Hypoxia
- Medical subject headings
- Retinal Artery Occlusion, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HypoxiaBiological
The purpose is to test the effect of A2A adrenoceptor stimulation on the diameter of retinal arterioles during hypoxia in vivo
RegadenosonDrug
Also called Rapiscan
The purpose is to test the effect of A2A adrenoceptor stimulation on the diameter of retinal arterioles during hypoxia in vivo
| Study group | Role | What they receive |
|---|---|---|
| Healthy person | Experimental | The purpose is to investigate the effect of A2A adrenoceptor stimulation using the drug regadenoson (Rapiscan) on the diameter of retinal arterioles during hypoxia in vivo. Receives: Biological: Hypoxia; Drug: Regadenoson |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diameter responses of retinal arterioles
The main outcome variable of the DVA is the width measurement of the selected vessel(s), expressed in units of measurement (UM). In a normal Gullstrand eye, 1 UM is equivalent to 1 µm. For the stimulation with flicker light, the outcome is defined as the percent change from baseline.
Measured: 11 minutes
Secondary outcomes (3)
Blood pressure
mmHg
Measured: The blood pressure is measured during the last 40 seconds in each phase using an oscillometric technique on the left arm.
Systemic arterial saturation
Percentage
Measured: The systemic arterial saturation is registered at the beginning and half way through each examination phase and during the 2 min break where the drug Regadenoson is injected.
Intraocular pressure
mmHg
Measured: The intraocular pressure is measured before and after the drug administration (time point 280 and 350 sec) and after the second DVA examination is terminated (time point 670 sec).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2017
- Study start22 Mar 2017
- Primary completionNov 2017 (estimated)
- Study completionNov 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Retinal Artery OcclusionStudies of the same condition, open and under way.
- More trials run by University of AarhusThe 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 2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The project will be conducted as an open controlled interventional study performed on two days separated by at least one day. The test persons will be randomly allocated to two groups, one group in which protocol 1 is followed by protocol 2, and the other group with the two protocols performed in the reverse order. Protocol 1: A) Using a Dynamic Vessel Analyzer, the diameter of a larger retinal vascular arcade arteriole will be recorded for 90 seconds at baseline followed by a similar recording during stimulation with flickering light and a recording during rest, altogether lasting 4.5 minutes. B) Intravenous injection of 0,4 mg regadenoson and repetition of the procedures in step A. Protocol 2: The procedures are similar to those of protocol 1 but are performed during breathing of a hypoxic gas mixture.
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Toke Bek, Chair, Study chair, Main supervisor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03090087
- Sponsor's protocol ID
- Adenosine RVA
- Status last verified
- Mar 2017
- First submitted
- 10 Mar 2017
- Last updated
- 28 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The project results will be published in recognized international journals. Both positive, negative and inconclusive results will be published.
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of A2A Adrenoceptor Stimulation on the Diameter of Retinal Arterioles During Hypoxia in Vivo
- ClinicalTrials.gov ID
- NCT03090087
- Acronym / sponsor ID
- Adenosine RVA
- Conditions
- Retinal Artery Occlusion
- Keywords
- Diameter of retinal arteries, Adenosine, Hypoxia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Study start
- 22 Mar 2017 (actual)
- Primary completion
- Nov 2017 (estimated)
- Study completion
- Nov 2017 (estimated)
- First posted
- 24 Mar 2017 (actual)
- 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 is to investigate how the adenosine affects the diameter regulation of retinal arterioles during changes in oxygen tension. A deeper understanding of the mechanisms involved in diameter regulation of retinal arterioles during changes in oxygen tension can be used to obtain a more detailed understanding of diseases where changes in the diameter regulation of retinal vessels are involved in the disease pathogenesis and possibly point to new therapeutic options for patients with retinal vascular disease, such as diabetic retinopathy and retinal vein thrombosis.
Preliminary, a routine ophthalmological evaluation, measurement of blood pressure, and electrocardiogram will be preformed to insure that only healthy test persons are included in the study.
The test persons will be randomly allocated to two groups, one group in which protocol 1 is followed by protocol 2, and the other group with the two protocols performed in the reverse order.
Protocol 1: Using the DVA, a video recording will capture the diameter of retinal vessels and the changes occurring during stimulation with flickering light. The recording lasts 4.5 minutes and is preformed before and after intravenous injection of adenosine.
Protocol 2: The procedures are similar to those of protocol 1 but are performed during breathing of a gas mixture with a reduced oxygen tension to 12,5 %, which results in a reduced oxygen saturation in the blood to 85-90 %.
Detailed description
Background:
Occlusion of the retinal vessels leading to retinal ischaemia and hypoxia is an important element in the pathophysiology of the major vision threatening diseases in the Western World. The hypoxic areas release vasodilating factors that induce vasodilatation in adjacent retinal areas in order to increase blood flow and retinal oxygenation. An understanding of the mechanisms underlying this vasodilatation may help identifying new therapeutic principles for modulating retinal blood flow during changes in retinal blood flow secondary to hypoxia and other diseases.
The present study:
Two working hypotheses will be tested: 1) That systemic administration of an A2A adrenoceptor agonist affects retinal blood flow independently of its systemic effects. 2) That the vasodilating effect of A2A adrenoceptor stimulation and the vasodilating effects of systemic hypoxia and increased retinal metabolism induced by flicker stimulation are additive.
Methods:
The diameter of retinal vessels are measured using the Dynamic Vessel Analyser (DVA). This apparatus performs video recordings of the ocular fundus, and the single images in the video sequences are grabbed for computerised analysis. Special software enables calculation of the diameter of the vessel on the basis of the distance between the vessel borders. The fact that images are grabbed real time (25 times per second) allows the detection of immediate diameter changes when the retinal metabolism is increased by exposure to flickering light (metabolic autoregulation).
The A2A adrenoceptor agonist regadenoson is administered during continuous ECG monitoring as a single intravenous injection of 400 micrograms (5 ml) in an antecubital vein. No dose adjustments are necessary for body weight, age, renal og hepatic impairment. Due to a potential ischaemic effect of regadenoson, only persons with no history of arterial hypertension or cardiac disease and with normal blood pressure and ECG will be included.
The experiments will be performed during breathing of ambient air and after 10 minutes of breathing air containing 12.5% oxygen (corresponding to the saturation at an altitude of 4100 m), which induces a decline in the arterial oxygen saturation resulting in dilatation of retinal vessels.
Experimental design:
The project will be conducted as an open controlled interventional study performed on two days separated by at least one day. Initial a routine ophthalmological evaluation with a slit lamp examination, measurement of the intraocular pressure and ophthalmoscopy, supplemented with a measurement of central retinal thickness using optical coherence tomography scanning will be preformed as will measuring of ECG and blood pressure to make sure only healthy test persons are included.
The test persons will be randomly allocated to two groups, one group in which protocol 1 is followed by protocol 2, and the other group with the two protocols performed in the reverse order.
Protocol 1:
- Using the DVA, the diameter of a larger retinal vascular arcade arteriole will be recorded for 90 seconds at baseline followed by a similar recording during stimulation with flickering light and a recording during rest, altogether lasting 4.5 minutes B) Intravenous injection of 0,4 mg regadenoson and repetition of the procedures in step A
Protocol 2:
The procedures are similar to those of protocol 1 but are performed during breathing of a hypoxic gas mixture.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The project will be conducted as an open controlled interventional study performed on two days separated by at least one day. The test persons will be randomly allocated to two groups, one group in which protocol 1 is followed by protocol 2, and the other group with the two protocols performed in the reverse order. Protocol 1: A) Using a Dynamic Vessel Analyzer, the diameter of a larger retinal vascular arcade arteriole will be recorded for 90 seconds at baseline followed by a similar recording during stimulation with flickering light and a recording during rest, altogether lasting 4.5 minutes. B) Intravenous injection of 0,4 mg regadenoson and repetition of the procedures in step A. Protocol 2: The procedures are similar to those of protocol 1 but are performed during breathing of a hypoxic gas mixture.
| Arm | Type | Receives |
|---|---|---|
| Healthy person | Experimental | Biological: Hypoxia, Drug: RegadenosonThe purpose is to investigate the effect of A2A adrenoceptor stimulation using the drug regadenoson (Rapiscan) on the diameter of retinal arterioles during hypoxia in vivo. |
Who may qualify
- Ages
- 20 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Age 20-35
- Healthy, both current and prior
- Normal echocardiogram
- Signed and informed consent
Key exclusion criteria (7 listed)
- Former or current cardiovascular disease or high blood pressure
- Lung diseases incl. asthma or chronic obstructive pulmonary disease (COPD)
- Known eye disease or previously treated for an eye disease, particularly glaucoma and cataracts
- People taking medication, except birth control pills
- Persons who have or who have had epilepsy
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 |
|---|---|---|
| HypoxiaThe purpose is to test the effect of A2A adrenoceptor stimulation on the diameter of retinal arterioles during hypoxia in vivo | Biological | Healthy person |
| RegadenosonAlso: RapiscanThe purpose is to test the effect of A2A adrenoceptor stimulation on the diameter of retinal arterioles during hypoxia in vivo | Drug | Healthy person |
Primary outcome
Diameter responses of retinal arterioles
Time frame: 11 minutes
The main outcome variable of the DVA is the width measurement of the selected vessel(s), expressed in units of measurement (UM). In a normal Gullstrand eye, 1 UM is equivalent to 1 µm. For the stimulation with flicker light, the outcome is defined as the percent change from baseline.
3 secondary outcomes
Blood pressure
Time frame: The blood pressure is measured during the last 40 seconds in each phase using an oscillometric technique on the left arm.
Systemic arterial saturation
Time frame: The systemic arterial saturation is registered at the beginning and half way through each examination phase and during the 2 min break where the drug Regadenoson is injected.
Intraocular pressure
Time frame: The intraocular pressure is measured before and after the drug administration (time point 280 and 350 sec) and after the second DVA examination is terminated (time point 670 sec).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2017.
- Individual participant dataSharing planned: Yes. The project results will be published in recognized international journals. Both positive, negative and inconclusive results will be published.
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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.
Toke Bek, Chair study chair
Main supervisor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hypoxia and Regadenoson in people with Retinal Artery Occlusion, run by University of Aarhus at 1 site in Denmark.
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 4 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 28 Mar 2017. 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 Denmark. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Anna Dons-Jensen, Student (+45 78463250, annadonsjensen@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diameter responses of retinal arterioles (time frame: 11 minutes). 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 28 Mar 2017.