Diabetic RetinopathyPhase 2DRESSNCT01295775
Diabetic Retinopathy Sulodexide Study
A Phase 2 study testing sulodexide in people with Diabetic Retinopathy, run by Ajou University School of Medicine at 1 site in South Korea.
Trial summary
The aim of this phase 2 controlled placebo study is to assess the effectiveness of Sulodexide in the treatment of non proliferative (background) retinopathy in patients with Type 1 and Type 2 Diabetes Mellitus. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Retinopathy
- What is being tested?
- sulodexide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 127 participants
- Where
- 1 siteSouth Korea
- Study dates
- Feb 2009to May 2011
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with Type 1 or Type 2 Diabetes Mellitus
- Diabetes under good control with drugs for at least 6 months (Glycosylated hemoglobin <9% )
- Patients with 300um ≤ the thickness of retina by optical coherence tomography
- Patients with visual acuity test ≥0.4 (20/50)
- Non-proliferative (background) retinopathy assessed by fundus photography and fluorescein angiography according to Airlie House Classification and ETDRS
- Patients with non-proliferative (background) retinopathy attested by the presence of Hard exudates within grade 2 and 5
Show all 11Show fewer
- Patients with at leat one of the following lesions: Vascular leakages, Microaneurysms, Haemorrhages, Intraretinal microvascular abnormalities (IRMA)
- Patients with controlled Arterial Blood Pressure since the last 6 months (Diastolic Blood Pressure ≤90mmHg and Systolic Blood Pressure ≤130 mmHg) with or without medication
- Patients capable of conforming to the study protocol
- Patients who have given their free and informed consent
- The ability and willingness to comply with all study procedures
Who cannot join
- Diabetic Retinopathy which is being treated with laser therapy or should be treated with laser therapy before the end of the study
- Concomitant retinal disease due to causes other than diabetic microangiopathy
- Concomitant antihypertensive treatment, unless administered at stable dosage at least 6 months before the start of the study
- Concomitant Angiotensin-converting enzyme inhibitor / Angiotensin II receptor blocker therapy, unless administered at stable dosage for at least 6 months prior to the start of the study
- Concomitant Warfarin therapy
- Patients with laser therapy or intravitreal injection(avastin,steroid) within 3 months from enrolment
Show all 17Show fewer
- Concomitant treatment with hemorrheological, vasoactive drugs and antithrombotics except acetylsalicylic acid at stable dosage
- Patients with severe liver impairment (Child-Pugh classification C)
- Patients with severe renal insufficiency (creatinine >2.2 mg/dl)
- Patients with severe cardiac insufficiency (New York Heart Association classes 3 - 4)
- Patients with clinical history of diathesis and haemorrhagic disease
- Individual hypersensitivity toward the product, heparin, low molecular weight heparin or heparin-like products
- Intended or ascertained pregnancy or lactation
- Participation to a trial within the past 6 months
- Surgery or trauma within the past 6 months
- Planned surgical intervention within 6 months from enrolment
- Patients unable to conform to the study protocol
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Kangnam Sacred Heart Hospital, Colloge of Medicine, Hallym University
Seoul, 150-071
About this study
Official title: A Multicentre, Double-Blind, Randomised, Placebo Controlled Study of the Activity of Sulodexide in Diabetic Patients With Mild to Moderate Non-Proliferative Retinopathy
The aim of this phase 2 controlled placebo study is to assess the effectiveness of Sulodexide in the treatment of non proliferative (background) retinopathy in patients with Type 1 and Type 2 Diabetes Mellitus.
This is a multicentre, double-blind, randomised study involving patients affected by non proliferative (background) diabetic mild to moderate retinopathy.
Read more
This study will involve 130 patients (65 for each group). At baseline visit (T0), the Investigator will grade the ocular lesions due to diabetic retinopathy according to color fundus photographs and the fluorescein angiography examination. He will subsequently send the negatives of photographs and the images -or negatives when available- of fluorescein angiography to an off-site Assessor -unaware of the Investigator assessment- nominated to confirm the quality of the images and the grade of the lesions. After positive assessment of the Investigator, at T0 the eligible patient will be blindly allocated to one of the 2 treatment groups according to a computer-generated randomisation list provided by the Sponsor.
The following treatments will be administered for 360 days:
A (SULODEXIDE GROUP): 50 mg a day by oral route;
B (PLACEBO GROUP): Sulodexide placebo at the same schedule and for the same lengths of time as group A.
Before breaking the randomisation code at the end of the study, an independent off site assessor will evaluate the photographs according to the Airlie House Classification and following modification by Early treatment Diabetic Retinopathy Study (ETDRS) and fluorescein angiography according to ETDRS.
Read the detailed description
Diabetic retinopathy is the leading cause of blindness in adults (20 to 74 years old) in the industrialised countries, affecting from 2 to 5% of entire population. All the complications of diabetes such as diabetic retinopathy, are caused by the chronic hyperglycaemia. Although a good metabolic control with therapy lowers the blood glucose levels enough to preserve life, this does not permit complete euglycemia nor prevent the long-term complications of chronic supernormal levels of blood glucose. The excess glucose causes flux through the polyol pathway, which results in structural tissue modifications.
Diabetic retinopathy is mainly a vascular disease, primarily affecting the capillaries. The first ultrastructural and microscopic changes reported are retinal capillary basement membrane thickening and pericyte degeneration, both of which compromise the integrity of the capillary wall, followed by pericyte loss.
The glycosaminoglycans (GAGs) of the basal membrane are progressively substituted by collagen, leading to a modification in vascular permeability due to the altered anionic charge. These changes lead to the clinical appearance of vascular leakage from retinal capillaries followed by microaneurysms. The lack of integrity of the vessel wall leads to haemorrhages, and to microthrombosis, which are responsible for the first ischemic lesions. If the vascular leakage lasts for a long time, the lipidic fraction of leaked plasma deposits in the retina forming hard exudates.
The substitution of GAGs by collagen leads to a basal membrane thickening also in the kidney. As in the retina, the modification of permeability occurs in the renal glomeruli and induces the selective loss of proteins (albuminuria).
Recent papers show a specific modification in GAGs metabolism occurring in diabetic patients that could be the common pathogenetic mechanism of vascular diabetic failure. Therefore, diabetic retinopathy and diabetic nephropathy may be regarded as the result of the alteration of a common underlying molecular mechanism whose expression is the depletion of GAGs from the basement membrane in both retinal and glomerular capillaries. In agreement with the previous statement, the Wisconsin Epidemiologic Study of Diabetic Retinopathy concluded that microalbuminuria is associated cross-sectionally with the presence of retinopathy in diabetic patients.
The progress of the clinical symptoms of the disease despite glycaemic therapy points to address the research towards new drugs able to slow or reverse the vessel micro-abnormalities responsible for the microangiopathy typical of diabetic retinopathy. Furthermore, the similarities of the vessel lesions between diabetic retinopathy and diabetic nephropathy suggest that new molecules effective in one of the two conditions should be effective in the other pathology as well.
Sulodexide (fast moving heparin fraction 80% and dermatan sulfate 20%) is a GAG with a high trophism for vessel wall. Clinical studies showed its efficacy in decreasing both microalbuminuria and macroalbuminuria in diabetic patients, suggesting that it could be able to slowdown the nephropathy progression, actually by partially restoring the glomerular GAGs content.
Preliminary observations regarding the use of Sulodexide in patients suffering from diabetic retinopathy show significant reduction in hard exudates, thus indirectly pointing out a benefit of this GAG at the retinal capillary level.
Based on the above mentioned physiopathological considerations and experimental findings, the investigators deem appropriate to evaluate the effects of Sulodexide on the diabetic retinopathy by the present multicentre, double-blind, placebo-controlled clinical trial.
- Conditions
- Diabetic Retinopathy
- Being tested
- sulodexide
- Keywords
- diabetic retinopathy, sulodexide, hard exudates, microaneurysms, hemorrhages, intraretinal microvascular abnormalities
- Medical subject headings
- Diabetic Retinopathy, Microaneurysm, Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sulodexideDrug
Also called vessel due F
A (SULODEXIDE GROUP):
50 mg a day by oral route (1+1 capsules/day) for 360 days
B (PLACEBO GROUP):
Sulodexide placebo at the same schedule dosage and for the same lengths of time as group A.
| Study group | Role | What they receive |
|---|---|---|
| Sulodexide group | Active comparator | 50 mg of sulodexide a day will be administered by oral route (1+1 capsule/day) for 360 days Receives: Drug: sulodexide |
| Placebo group | Placebo comparator | Sulodexide placebo will be administered at the same schedule (1+1 capsule/day) and for the same lengths of time (for 360 days) as Sulodexide group Receives: Drug: sulodexide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hard exudates
The lesion will be evaluated by fundus photography and fluorescein angiography, graded according to Modefied Airlie House Classification and ETDRS.
Measured: T12: 360 +/- 7 days from T0
Secondary outcomes (4)
microaneurysms
The lesion will be evaluated by fundus photography and fluorescein angiography, graded according to Modefied Airlie House Classification and ETDRS.
Measured: T12: 360 +/- 7 days from T0
Vascular leakage
The lesion will be evaluated by fundus photography and fluorescein angiography, graded according to Modefied Airlie House Classification and ETDRS.
Measured: T12: 360 +/- 7 days from T0
Haemorrhages
The lesion will be evaluated by fundus photography and fluorescein angiography, graded according to Modefied Airlie House Classification and ETDRS.
Measured: T12: 360 +/- 7 days from T0
Intraretinal microvascular abnormalities (IRMA)
The lesion will be evaluated by fundus photography and fluorescein angiography, graded according to Modefied Airlie House Classification and ETDRS.
Measured: T12: 360 +/- 7 days from T0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2011 (estimated)
- Study startFeb 2009
- Primary completionApr 2011
- Study completionMay 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetic RetinopathyStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ajou University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ji Hun Song, Ajou University School of Medicine
- Investigators
- Ha Kyoung Kim, MD, Principal investigator, Department of Ophthalmology, Kangnam Sacred Heart Hospital, College of Medicine, Hallym University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01295775
- Sponsor's protocol ID
- DRESS_Korea
- Acronym
- DRESS
- Status last verified
- Nov 2012
- First submitted
- 22 Jul 2010
- Last updated
- 6 Nov 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Song JH, Chin HS, Kwon OW, Lim SJ, Kim HK; DRESS Research Group. Effect of sulodexide in patients with non-proliferative diabetic retinopathy: diabetic retinopathy sulodexide study (DRESS). Graefes Arch Clin Exp Ophthalmol. 2015 Jun;253(6):829-37. doi: 10.1007/s00417-014-2746-8. Epub 2014 Aug 12.
PubMed 25112845
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre, Double-Blind, Randomised, Placebo Controlled Study of the Activity of Sulodexide in Diabetic Patients With Mild to Moderate Non-Proliferative Retinopathy
- ClinicalTrials.gov ID
- NCT01295775
- Acronym / sponsor ID
- DRESS / DRESS_Korea
- Conditions
- Diabetic Retinopathy
- Keywords
- diabetic retinopathy, sulodexide, hard exudates, microaneurysms, hemorrhages, intraretinal microvascular abnormalities
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 127 participants (actual)
- Lead sponsor
- Ajou University School of MedicineUniversity, hospital or other
- Study start
- Feb 2009
- Primary completion
- Apr 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 15 Feb 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.
The aim of this phase 2 controlled placebo study is to assess the effectiveness of Sulodexide in the treatment of non proliferative (background) retinopathy in patients with Type 1 and Type 2 Diabetes Mellitus.
This is a multicentre, double-blind, randomised study involving patients affected by non proliferative (background) diabetic mild to moderate retinopathy.
This study will involve 130 patients (65 for each group). At baseline visit (T0), the Investigator will grade the ocular lesions due to diabetic retinopathy according to color fundus photographs and the fluorescein angiography examination. He will subsequently send the negatives of photographs and the images -or negatives when available- of fluorescein angiography to an off-site Assessor -unaware of the Investigator assessment- nominated to confirm the quality of the images and the grade of the lesions. After positive assessment of the Investigator, at T0 the eligible patient will be blindly allocated to one of the 2 treatment groups according to a computer-generated randomisation list provided by the Sponsor.
The following treatments will be administered for 360 days:
A (SULODEXIDE GROUP): 50 mg a day by oral route;
B (PLACEBO GROUP): Sulodexide placebo at the same schedule and for the same lengths of time as group A.
Before breaking the randomisation code at the end of the study, an independent off site assessor will evaluate the photographs according to the Airlie House Classification and following modification by Early treatment Diabetic Retinopathy Study (ETDRS) and fluorescein angiography according to ETDRS.
Detailed description
Diabetic retinopathy is the leading cause of blindness in adults (20 to 74 years old) in the industrialised countries, affecting from 2 to 5% of entire population. All the complications of diabetes such as diabetic retinopathy, are caused by the chronic hyperglycaemia. Although a good metabolic control with therapy lowers the blood glucose levels enough to preserve life, this does not permit complete euglycemia nor prevent the long-term complications of chronic supernormal levels of blood glucose. The excess glucose causes flux through the polyol pathway, which results in structural tissue modifications.
Diabetic retinopathy is mainly a vascular disease, primarily affecting the capillaries. The first ultrastructural and microscopic changes reported are retinal capillary basement membrane thickening and pericyte degeneration, both of which compromise the integrity of the capillary wall, followed by pericyte loss.
The glycosaminoglycans (GAGs) of the basal membrane are progressively substituted by collagen, leading to a modification in vascular permeability due to the altered anionic charge. These changes lead to the clinical appearance of vascular leakage from retinal capillaries followed by microaneurysms. The lack of integrity of the vessel wall leads to haemorrhages, and to microthrombosis, which are responsible for the first ischemic lesions. If the vascular leakage lasts for a long time, the lipidic fraction of leaked plasma deposits in the retina forming hard exudates.
The substitution of GAGs by collagen leads to a basal membrane thickening also in the kidney. As in the retina, the modification of permeability occurs in the renal glomeruli and induces the selective loss of proteins (albuminuria).
Recent papers show a specific modification in GAGs metabolism occurring in diabetic patients that could be the common pathogenetic mechanism of vascular diabetic failure. Therefore, diabetic retinopathy and diabetic nephropathy may be regarded as the result of the alteration of a common underlying molecular mechanism whose expression is the depletion of GAGs from the basement membrane in both retinal and glomerular capillaries. In agreement with the previous statement, the Wisconsin Epidemiologic Study of Diabetic Retinopathy concluded that microalbuminuria is associated cross-sectionally with the presence of retinopathy in diabetic patients.
The progress of the clinical symptoms of the disease despite glycaemic therapy points to address the research towards new drugs able to slow or reverse the vessel micro-abnormalities responsible for the microangiopathy typical of diabetic retinopathy. Furthermore, the similarities of the vessel lesions between diabetic retinopathy and diabetic nephropathy suggest that new molecules effective in one of the two conditions should be effective in the other pathology as well.
Sulodexide (fast moving heparin fraction 80% and dermatan sulfate 20%) is a GAG with a high trophism for vessel wall. Clinical studies showed its efficacy in decreasing both microalbuminuria and macroalbuminuria in diabetic patients, suggesting that it could be able to slowdown the nephropathy progression, actually by partially restoring the glomerular GAGs content.
Preliminary observations regarding the use of Sulodexide in patients suffering from diabetic retinopathy show significant reduction in hard exudates, thus indirectly pointing out a benefit of this GAG at the retinal capillary level.
Based on the above mentioned physiopathological considerations and experimental findings, the investigators deem appropriate to evaluate the effects of Sulodexide on the diabetic retinopathy by the present multicentre, double-blind, placebo-controlled clinical trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sulodexide group | Active comparator | Drug: sulodexide50 mg of sulodexide a day will be administered by oral route (1+1 capsule/day) for 360 days |
| Placebo group | Placebo comparator | Drug: sulodexideSulodexide placebo will be administered at the same schedule (1+1 capsule/day) and for the same lengths of time (for 360 days) as Sulodexide group |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients with Type 1 or Type 2 Diabetes Mellitus
- Diabetes under good control with drugs for at least 6 months (Glycosylated hemoglobin <9% )
- Patients with 300um ≤ the thickness of retina by optical coherence tomography
- Patients with visual acuity test ≥0.4 (20/50)
- Non-proliferative (background) retinopathy assessed by fundus photography and fluorescein angiography according to Airlie House Classification and ETDRS
Key exclusion criteria (17 listed)
- Diabetic Retinopathy which is being treated with laser therapy or should be treated with laser therapy before the end of the study
- Concomitant retinal disease due to causes other than diabetic microangiopathy
- Concomitant antihypertensive treatment, unless administered at stable dosage at least 6 months before the start of the study
- Concomitant Angiotensin-converting enzyme inhibitor / Angiotensin II receptor blocker therapy, unless administered at stable dosage for at least 6 months prior to the start of the study
- Concomitant Warfarin therapy
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 |
|---|---|---|
| sulodexideAlso: vessel due FA (SULODEXIDE GROUP): 50 mg a day by oral route (1+1 capsules/day) for 360 days B (PLACEBO GROUP): Sulodexide placebo at the same schedule dosage and for the same lengths of time as group A. | Drug | Placebo group, Sulodexide group |
Primary outcome
Hard exudates
Time frame: T12: 360 +/- 7 days from T0
The lesion will be evaluated by fundus photography and fluorescein angiography, graded according to Modefied Airlie House Classification and ETDRS.
4 secondary outcomes
microaneurysms
Time frame: T12: 360 +/- 7 days from T0
Vascular leakage
Time frame: T12: 360 +/- 7 days from T0
Haemorrhages
Time frame: T12: 360 +/- 7 days from T0
Intraretinal microvascular abnormalities (IRMA)
Time frame: T12: 360 +/- 7 days from T0
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 6 Nov 2012.
- Derived from this study: PubMed 25112845Song JH, Chin HS, Kwon OW, Lim SJ, Kim HK; DRESS Research Group. Effect of sulodexide in patients with non-proliferative diabetic retinopathy: diabetic retinopathy sulodexide study (DRESS). Graefes Arch Clin Exp Ophthalmol. 2015 Jun;253(6):829-37. doi: 10.1007/s00417-014-2746-8. Epub 2014 Aug 12.
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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.
Ha Kyoung Kim, MD principal investigator
Department of Ophthalmology, Kangnam Sacred Heart Hospital, College of Medicine, Hallym University
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 sulodexide in people with Diabetic Retinopathy, run by Ajou University School of Medicine at 1 site in South Korea.
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 11 inclusion and 17 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 6 Nov 2012. 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 South Korea. 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. Some participants in this study may receive a placebo. 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?
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?
Hard exudates (time frame: T12: 360 +/- 7 days from T0). 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 NCT01295775, which also lists 1 linked publication.
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 6 Nov 2012.