Complications of Diabetes MellitusNCT02718547
The Relationship Between Intraocular Pressure and Macular Edema in Patients With Diabetic Macular Edema
A study testing Combigan in people with Complications of Diabetes Mellitus, run by Meir Medical Center at 1 site in Israel.
Trial summary
The Investigators propose to examine the effect of lowering the intraocular pressure on macular edema in Participants diagnosed with diabetic macular edema. Our theory is based on the assumption that lower intraocular pressure means higher Ocular Perfusion pressure, which may cause an improvement in retinal perfusion… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Complications of Diabetes Mellitus
- What is being tested?
- Combigan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteIsrael
- Study dates
- 26 Mar 2017to Jul 2018
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants with a diagnosis of diabetic macular edema over the age of 18 which are eligible to sign an agreement to participate in the study
- Presence of DME (based on clinical examination of retinal specialist + OCT) in both eyes with an edema thickness ranged from 350 to 800 microns
- Media lucid enough to allow sufficient quality photographs by OCT
Who cannot join
- Patients which do not have a valid diagnosis of DME (Diabetic Macular Edema)
- Patients with problems that can cause macular edema in any other:
- Age-Related Macular Degeneration
- Central retinal vein occlusion (CRVO)/Branch retinal vein occlusion (BRVO) /central retinal artery occlusion (CRAO) / branch retinal artery occlusion (BRAO)
- Epiretinal membrane (ERM) or Vitreo-macular traction (VMT)
- Patients who are Pseudophakic in one eye or pseudophakic in both eyes for less than a year
Show all 12Show fewer
- Patients treated in order to reduce the DME by intra-vitreal injection or by laser in the past six months
- Patients which are currently treat with Intra ocular Pressure lowering drops in at least one eye, or have been treated in the past with laser of any kind or with surgery
- Patients who underwent Pars plana vitrectomy one or both eyes
- Patients who cannot undergo an OCT examination
- Patients who want prefer to be treated by the current practices based on clinical judgment
- Patients with a condition that requires an intervention or laser surgery during the 3 months of study, such as active Proliferative diabetic retinopathy, vitreous hemorrhage or other similar conditions
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
Meir Medical center
Kfar Saba, Israel, 69419
Nimrod Dar, MD, +972545937757, nimrod.dar@gmail.com
About this study
Official title: The Effect of Reducing the Intraocular Pressure by Using Alphagan Drops and Macular Edema in Patients With Diabetic Macular Edema
The Investigators propose to examine the effect of lowering the intraocular pressure on macular edema in Participants diagnosed with diabetic macular edema. Our theory is based on the assumption that lower intraocular pressure means higher Ocular Perfusion pressure, which may cause an improvement in retinal perfusion and thus an improvement in retinal oxygenation and reduced edema
Read the detailed description
Ocular perfusion pressure (ocular perfusion pressure - OPP), considered the driving force of ocular blood flow. Perfusion pressure is defined as the difference between the artery and vein blood pressure. Because ocular venous pressure is the same or slightly higher than the IOP (intra ocular pressure - IOP), it is common to estimate the OPP as the difference between the arterial blood pressure of IOP. The OPP is critical for diffusion of oxygen, nutrients and metabolic waste from retinal imaging, and decrease it may reduce blood flow to the eye and lead to ischemia or hypoxia. the OPP is controlled by a complex system of Autoregulation. Much has been written about the relationship between the OPP and glaucoma, and agreed that OPP is a low risk factor for this disease.
Diabetic macular edema (DME) is the most common cause of vision loss in developed countries the working-age.
Many studies were carried out in recent years in an attempt to better understand the pathophysiology of Diabetic macular edema, and there is consensus in the scientific literature that hypertension have a significant effect on Diabetic macular edema. this relationship is much more complex than it seems at first glance. Paques and his team have shown an inverse association between blood pressure to drop night and Diabetic macular edema. LARSEN and his team have shown a similar trend.
Hayreh published an article from 2007, where he described the mechanism of improvement of the Diabetic macular edema with discontinuation of hypertensive treatment and thereby raising blood pressure. In this article, Hayreh describes hypoxia as a significant factor in Diabetic macular edema, and demonstrated that treatment of hypoxia by increasing the OPP brought good results in terms of macular thickness If so, it seems that there is not only a link between levels of oxygenation of the retina to Diabetic macular edema, but that improved oxygenation of the retina could lower the levels of macular edema in these patients. If a way were found to improve retinal perfusion, this may lead to an improved oxygenation and reduced edema. The Investigators propose to examine the relationship between macular edema IOP in Participants with Diabetic macular edema, thinking that high IOP means lower OPP, which means increased risk for developing macular edema in this Participants group.
- Conditions
- Complications of Diabetes Mellitus
- Being tested
- Combigan
- Keywords
- Diabetes mellitus, Diabetic macular edema, Intra ocular pressure, Ocular perfusion pressure, Retinal perfusion
- Medical subject headings
- Diabetes Complications, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CombiganDrug
Also called brimonidine tartrate/timolol maleate ophthalmic solution
Each Participant will be instructed to instill Combigan eye drops twice daily in one of his eyes (randomly chosen)
| Study group | Role | What they receive |
|---|---|---|
| Participants receiving Combigan drops in order to reduce IOP | Experimental | All of the Participants in this study will be instructed to instill combigan eye drops twice daily in one eye (randomly chosen) Receives: Drug: Combigan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of at least 50 micron in Macular edema
The participants will be examined every month from the time of recruitment as mentioned before, at each visit the Macular Edema will be assessed, but the Outcome measure will be defined as Change of at least 50 Micron in Macular Edema at the third visit, 3 months from recruitment
Measured: Baseline measurement will be conducted at the recruitment of the participant, the second measurement will be preformed after one moth from recruitment and the third and last measurement will be preformed after 3 months from recruitment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2016 (estimated)
- Study start26 Mar 2017
- Primary completion30 Mar 2018 (estimated)
- Study completionJul 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Complications of Diabetes MellitusStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Meir Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Meir Hospital, Kfar Saba, Israel
- Responsible party
- Principal investigator, Avner Belkin, Meir Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02718547
- Sponsor's protocol ID
- 0029-16-MMC
- Status last verified
- Mar 2017
- First submitted
- 6 Mar 2016
- Last updated
- 28 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Glucksberg MR, Dunn R. Direct measurement of retinal microvascular pressures in the live, anesthetized cat. Microvasc Res. 1993 Mar;45(2):158-65. doi: 10.1006/mvre.1993.1015.
PubMed 8361399Schmidl D, Garhofer G, Schmetterer L. The complex interaction between ocular perfusion pressure and ocular blood flow - relevance for glaucoma. Exp Eye Res. 2011 Aug;93(2):141-55. doi: 10.1016/j.exer.2010.09.002. Epub 2010 Sep 22.
PubMed 20868686Thomas BJ, Shienbaum G, Boyer DS, Flynn HW Jr. Evolving strategies in the management of diabetic macular edema: clinical trials and current management. Can J Ophthalmol. 2013 Feb;48(1):22-30. doi: 10.1016/j.jcjo.2012.11.012.
PubMed 23419295Lasker RD. The diabetes control and complications trial. Implications for policy and practice. N Engl J Med. 1993 Sep 30;329(14):1035-6. doi: 10.1056/NEJM199309303291410. No abstract available.
PubMed 8366905Klein R, Klein BE, Moss SE, Cruickshanks KJ. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XV. The long-term incidence of macular edema. Ophthalmology. 1995 Jan;102(1):7-16. doi: 10.1016/s0161-6420(95)31052-4.
PubMed 7831044Bhagat N, Grigorian RA, Tutela A, Zarbin MA. Diabetic macular edema: pathogenesis and treatment. Surv Ophthalmol. 2009 Jan-Feb;54(1):1-32. doi: 10.1016/j.survophthal.2008.10.001.
PubMed 19171208Matthews DR, Stratton IM, Aldington SJ, Holman RR, Kohner EM; UK Prospective Diabetes Study Group. Risks of progression of retinopathy and vision loss related to tight blood pressure control in type 2 diabetes mellitus: UKPDS 69. Arch Ophthalmol. 2004 Nov;122(11):1631-40. doi: 10.1001/archopht.122.11.1631.
PubMed 15534123Paques M, Massin P, Sahel JA, Gaudric A, Bergmann JF, Azancot S, Levy BI, Vicaut E. Circadian fluctuations of macular edema in patients with morning vision blurring: correlation with arterial pressure and effect of light deprivation. Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4707-11. doi: 10.1167/iovs.05-0638.
PubMed 16303968Larsen M, Wang M, Sander B. Overnight thickness variation in diabetic macular edema. Invest Ophthalmol Vis Sci. 2005 Jul;46(7):2313-6. doi: 10.1167/iovs.04-0893.
PubMed 15980216Hayreh SS. Role of retinal hypoxia in diabetic macular edema: a new concept. Graefes Arch Clin Exp Ophthalmol. 2008 Mar;246(3):353-61. doi: 10.1007/s00417-007-0678-2. Epub 2007 Sep 18.
PubMed 17876597Vinten M, La Cour M, Lund-Andersen H, Larsen M. Acute effect of pure oxygen breathing on diabetic macular edema. Eur J Ophthalmol. 2012 Aug 8:0. doi: 10.5301/ejo.5000195. Online ahead of print.
PubMed 22890599Nguyen QD, Shah SM, Van Anden E, Sung JU, Vitale S, Campochiaro PA. Supplemental oxygen improves diabetic macular edema: a pilot study. Invest Ophthalmol Vis Sci. 2004 Feb;45(2):617-24. doi: 10.1167/iovs.03-0557.
PubMed 14744906Vinten M, la Cour M, Lund-Andersen H, Larsen M. Effect of acute postural variation on diabetic macular oedema. Acta Ophthalmol. 2010 Mar;88(2):174-80. doi: 10.1111/j.1755-3768.2008.01421.x. Epub 2009 Dec 13.
PubMed 19094166Frederiksen CA, Jeppesen P, Knudsen ST, Poulsen PL, Mogensen CE, Bek T. The blood pressure-induced diameter response of retinal arterioles decreases with increasing diabetic maculopathy. Graefes Arch Clin Exp Ophthalmol. 2006 Oct;244(10):1255-61. doi: 10.1007/s00417-006-0262-1. Epub 2006 Mar 15.
PubMed 16538448
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 Reducing the Intraocular Pressure by Using Alphagan Drops and Macular Edema in Patients With Diabetic Macular Edema
- ClinicalTrials.gov ID
- NCT02718547
- Acronym / sponsor ID
- 0029-16-MMC
- Conditions
- Complications of Diabetes Mellitus
- Keywords
- Diabetes mellitus, Diabetic macular edema, Intra ocular pressure, Ocular perfusion pressure, Retinal perfusion
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Meir Medical CenterUniversity, hospital or other
- Collaborators
- Meir Hospital, Kfar Saba, Israel
- Study start
- 26 Mar 2017 (actual)
- Primary completion
- 30 Mar 2018 (estimated)
- Study completion
- Jul 2018 (estimated)
- First posted
- 24 Mar 2016 (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.
The Investigators propose to examine the effect of lowering the intraocular pressure on macular edema in Participants diagnosed with diabetic macular edema. Our theory is based on the assumption that lower intraocular pressure means higher Ocular Perfusion pressure, which may cause an improvement in retinal perfusion and thus an improvement in retinal oxygenation and reduced edema
Detailed description
Ocular perfusion pressure (ocular perfusion pressure - OPP), considered the driving force of ocular blood flow. Perfusion pressure is defined as the difference between the artery and vein blood pressure. Because ocular venous pressure is the same or slightly higher than the IOP (intra ocular pressure - IOP), it is common to estimate the OPP as the difference between the arterial blood pressure of IOP. The OPP is critical for diffusion of oxygen, nutrients and metabolic waste from retinal imaging, and decrease it may reduce blood flow to the eye and lead to ischemia or hypoxia. the OPP is controlled by a complex system of Autoregulation. Much has been written about the relationship between the OPP and glaucoma, and agreed that OPP is a low risk factor for this disease.
Diabetic macular edema (DME) is the most common cause of vision loss in developed countries the working-age.
Many studies were carried out in recent years in an attempt to better understand the pathophysiology of Diabetic macular edema, and there is consensus in the scientific literature that hypertension have a significant effect on Diabetic macular edema. this relationship is much more complex than it seems at first glance. Paques and his team have shown an inverse association between blood pressure to drop night and Diabetic macular edema. LARSEN and his team have shown a similar trend.
Hayreh published an article from 2007, where he described the mechanism of improvement of the Diabetic macular edema with discontinuation of hypertensive treatment and thereby raising blood pressure. In this article, Hayreh describes hypoxia as a significant factor in Diabetic macular edema, and demonstrated that treatment of hypoxia by increasing the OPP brought good results in terms of macular thickness If so, it seems that there is not only a link between levels of oxygenation of the retina to Diabetic macular edema, but that improved oxygenation of the retina could lower the levels of macular edema in these patients. If a way were found to improve retinal perfusion, this may lead to an improved oxygenation and reduced edema. The Investigators propose to examine the relationship between macular edema IOP in Participants with Diabetic macular edema, thinking that high IOP means lower OPP, which means increased risk for developing macular edema in this Participants group.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participants receiving Combigan drops in order to reduce IOP | Experimental | Drug: CombiganAll of the Participants in this study will be instructed to instill combigan eye drops twice daily in one eye (randomly chosen) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Participants with a diagnosis of diabetic macular edema over the age of 18 which are eligible to sign an agreement to participate in the study
- Presence of DME (based on clinical examination of retinal specialist + OCT) in both eyes with an edema thickness ranged from 350 to 800 microns
- Media lucid enough to allow sufficient quality photographs by OCT
Key exclusion criteria (12 listed)
- Patients which do not have a valid diagnosis of DME (Diabetic Macular Edema)
- Patients with problems that can cause macular edema in any other:
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 |
|---|---|---|
| CombiganAlso: brimonidine tartrate/timolol maleate ophthalmic solutionEach Participant will be instructed to instill Combigan eye drops twice daily in one of his eyes (randomly chosen) | Drug | Participants receiving Combigan drops in order to reduce IOP |
Primary outcome
Change of at least 50 micron in Macular edema
Time frame: Baseline measurement will be conducted at the recruitment of the participant, the second measurement will be preformed after one moth from recruitment and the third and last measurement will be preformed after 3 months from recruitment
The participants will be examined every month from the time of recruitment as mentioned before, at each visit the Macular Edema will be assessed, but the Outcome measure will be defined as Change of at least 50 Micron in Macular Edema at the third visit, 3 months from recruitment
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.
- Background: PubMed 8361399Glucksberg MR, Dunn R. Direct measurement of retinal microvascular pressures in the live, anesthetized cat. Microvasc Res. 1993 Mar;45(2):158-65. doi: 10.1006/mvre.1993.1015.
- Background: PubMed 20868686Schmidl D, Garhofer G, Schmetterer L. The complex interaction between ocular perfusion pressure and ocular blood flow - relevance for glaucoma. Exp Eye Res. 2011 Aug;93(2):141-55. doi: 10.1016/j.exer.2010.09.002. Epub 2010 Sep 22.
- Background: PubMed 23419295Thomas BJ, Shienbaum G, Boyer DS, Flynn HW Jr. Evolving strategies in the management of diabetic macular edema: clinical trials and current management. Can J Ophthalmol. 2013 Feb;48(1):22-30. doi: 10.1016/j.jcjo.2012.11.012.
- Background: PubMed 8366905Lasker RD. The diabetes control and complications trial. Implications for policy and practice. N Engl J Med. 1993 Sep 30;329(14):1035-6. doi: 10.1056/NEJM199309303291410. No abstract available.
- Background: PubMed 7831044Klein R, Klein BE, Moss SE, Cruickshanks KJ. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XV. The long-term incidence of macular edema. Ophthalmology. 1995 Jan;102(1):7-16. doi: 10.1016/s0161-6420(95)31052-4.
- Background: PubMed 19171208Bhagat N, Grigorian RA, Tutela A, Zarbin MA. Diabetic macular edema: pathogenesis and treatment. Surv Ophthalmol. 2009 Jan-Feb;54(1):1-32. doi: 10.1016/j.survophthal.2008.10.001.
- Background: PubMed 15534123Matthews DR, Stratton IM, Aldington SJ, Holman RR, Kohner EM; UK Prospective Diabetes Study Group. Risks of progression of retinopathy and vision loss related to tight blood pressure control in type 2 diabetes mellitus: UKPDS 69. Arch Ophthalmol. 2004 Nov;122(11):1631-40. doi: 10.1001/archopht.122.11.1631.
- Background: PubMed 16303968Paques M, Massin P, Sahel JA, Gaudric A, Bergmann JF, Azancot S, Levy BI, Vicaut E. Circadian fluctuations of macular edema in patients with morning vision blurring: correlation with arterial pressure and effect of light deprivation. Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4707-11. doi: 10.1167/iovs.05-0638.
- Background: PubMed 15980216Larsen M, Wang M, Sander B. Overnight thickness variation in diabetic macular edema. Invest Ophthalmol Vis Sci. 2005 Jul;46(7):2313-6. doi: 10.1167/iovs.04-0893.
- Background: PubMed 17876597Hayreh SS. Role of retinal hypoxia in diabetic macular edema: a new concept. Graefes Arch Clin Exp Ophthalmol. 2008 Mar;246(3):353-61. doi: 10.1007/s00417-007-0678-2. Epub 2007 Sep 18.
- Background: PubMed 22890599Vinten M, La Cour M, Lund-Andersen H, Larsen M. Acute effect of pure oxygen breathing on diabetic macular edema. Eur J Ophthalmol. 2012 Aug 8:0. doi: 10.5301/ejo.5000195. Online ahead of print.
- Background: PubMed 14744906Nguyen QD, Shah SM, Van Anden E, Sung JU, Vitale S, Campochiaro PA. Supplemental oxygen improves diabetic macular edema: a pilot study. Invest Ophthalmol Vis Sci. 2004 Feb;45(2):617-24. doi: 10.1167/iovs.03-0557.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Combigan in people with Complications of Diabetes Mellitus, run by Meir Medical Center at 1 site in Israel.
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 3 inclusion and 12 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 Israel. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nimrod Dar, MD (+972545937757, nimrod.dar@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of at least 50 micron in Macular edema (time frame: Baseline measurement will be conducted at the recruitment of the participant, the second measurement will be preformed after one moth from recruitment and the third and last measurement will be preformed after 3 months from recruitment). 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 NCT02718547, which also lists 14 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 28 Mar 2017.