Clinical trial NCT01726075: Trial to Assess the Efficacy of Neuroprotective Drugs Administered Topically to Prevent or Arrest Diabetic Retinopathy
Official title: Neurodegeneration as Early Event in Pathogenesis of Diabetic Retinopathy:Multicentric, Prospective, Ph. II-III,Random.Controlled Trial to Assess Efficacy of Neuroprotective Drugs Administered Topically to Prevent/Arrest Diabetic Retinopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Diabetic Retinopathy
Keywords: diabetic retinopathy
Lead sponsor: BCN Peptides
Sponsor class: INDUSTRY
First posted: 2012-11-14
Enrollment: 450
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: To assess whether neuroprotective drugs administered topically (somatostatin and brimonidine) are able to prevent or arrest the development and progression of neurodegenerative changes

Detailed description: To assess whether neuroprotective drugs administered topically (somatostatin and brimonidine) are able to prevent or arrest the development and progression of neurodegenerative changes related to diabetic retinopathy.

Eligibility criteria: Inclusion Criteria:

1. Patients with type 2 diabetes mellitus
2. Diabetes duration ≥ 5 years
3. Aged between 45-75 years-old
4. ETDRS level \< 20 (microaneurysms absent) (50% of enrolled patients) Or ETDRS levels 20 or 35 with presence of at least one microaneurysm in Field 2 between the superior and inferior arcades (50% of enrolled patients) in the Study Eye as determined by the Reading Centre.
5. Informed Consent

Exclusion Criteria:

1. Previous laser photocoagulation
2. Other diseases which may induce retinal degeneration (e.g. glaucoma)
3. Subject with a refractive error ≥ ± 5 diopter
4. Inadequate ocular media and/ or pupil dilatation that do not permit good quality fundus photography.
5. Renal failure (creatinine \> 1.4 mg/dl)
6. HbA1C \> 10 % in the previous 6 months and at Screening
7. Subjects taking somatostatin or brimonidine, for any indication, in the previous 3 months
8. Subject has a condition or is in a situation which may put the subject at significant risk, may confound the study results or may interfere significantly with the patient's participation in the study.
9. Pregnancy or nursing
10. Hypersensitivity to the active substances to be tested or to any of the excipients
11. Subject receiving systemic monoamine oxidase (MAO) inhibitor therapy or antidepressants which affect noradrenergic transmission (e.g. tricyclic antidepressants and mianserin)

Primary outcomes:
measure: Changes in the Implicit Time assessed by mfERG (IT-mfERG) at month 6, 12, 18 and 24
timeFrame: month 24
Secondary outcomes:
measure: Retinal Nerve Fiber Layer (RNFL) assessed by Spectral Domain Optical Coherence Tomography (SD-OCT) at month 0
timeFrame: month 0
measure: Retinal Nerve Fiber Layer (RNFL) assessed by SD-OCT at month 6
timeFrame: month 6
measure: Retinal Nerve Fiber Layer (RNFL) assessed by SD-OCT at month 12
timeFrame: month 12
measure: Retinal Nerve Fiber Layer (RNFL) assessed by SD-OCT at month 18
timeFrame: month 18
measure: Retinal Nerve Fiber Layer (RNFL) assessed by SD-OCT at month 24
timeFrame: month 24
measure: Ganglion Cell Layer (GCL) assessed by SD-OCT at month 0
timeFrame: month 0
measure: Ganglion Cell Layer (GCL) assessed by SD-OCT at month 6
timeFrame: month 6
measure: Ganglion Cell Layer (GCL) assessed by SD-OCT at month 12
timeFrame: month 12
measure: Ganglion Cell Layer (GCL) assessed by SD-OCT at month 18
timeFrame: month 18
measure: Ganglion Cell Layer (GCL) assessed by SD-OCT at month 24
timeFrame: month 24
measure: Microaneurysm turnover assessed by Colour Fundus Photography (CFP - 45º/50º Field 2) at baseline
timeFrame: baseline
measure: Microaneurysm turnover assessed by Colour Fundus Photography (CFP - 45º/50º Field 2) at month 6
timeFrame: month 6
measure: Microaneurysm turnover assessed by Colour Fundus Photography (CFP - 45º/50º Field 2) at month 12
timeFrame: month 12
measure: Microaneurysm turnover assessed by Colour Fundus Photography (CFP - 45º/50º Field 2) at month 18
timeFrame: month 18
measure: Microaneurysm turnover assessed by Colour Fundus Photography (CFP - 45º/50º Field 2) at month 24
timeFrame: month 24
measure: Retinal thickness assessed by SD-OCT at month 0
timeFrame: month 0
measure: Retinal thickness assessed by SD-OCT at month 6
timeFrame: month 6
measure: Retinal thickness assessed by SD-OCT at month 12
timeFrame: month 12
measure: Retinal thickness assessed by SD-OCT at month 18
timeFrame: month 18
measure: Retinal thickness assessed by SD-OCT at month 24
timeFrame: month 24
measure: Central retinal thickness assessed by SD-OCT at month 0
timeFrame: month 0
measure: Central retinal thickness assessed by SD-OCT at month 6
timeFrame: month 6
measure: Central retinal thickness assessed by SD-OCT at month 12
timeFrame: month 12
measure: Central retinal thickness assessed by SD-OCT at month 18
timeFrame: month 18
measure: Central retinal thickness assessed by SD-OCT at month 24
timeFrame: month 24
measure: Diabetic Retinopathy (DR) severity assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) scale CFP - 30º/35º-7 fields at baseline
timeFrame: baseline
measure: DR severity assessed by ETDRS scale CFP - 30º/35º-7 fields at month 24
timeFrame: month 24
Other outcomes:
measure: Best Corrected Visual Acuity (BCVA) assessed by ETDRS scale at month 0
timeFrame: month 0
measure: BCVA assessed by ETDRS scale at month 6
timeFrame: month 6
measure: BCVA assessed by ETDRS scale at month 12
timeFrame: month 12
measure: BCVA assessed by ETDRS scale at month 18
timeFrame: month 18
measure: BCVA assessed by ETDRS scale at month 24
timeFrame: month 24
measure: Visual Fields defects assessed by Visual Fields Test at month 0
timeFrame: month 0
measure: Visual Fields defects assessed by Visual Fields Test at month 24
timeFrame: month 24
measure: Visual health assessed by Visual Function Questionnaire (VFQ-25) at month 0
timeFrame: month 0
measure: Visual health assessed by Visual Function Questionnaire (VFQ-25) at month 24
timeFrame: month 24
measure: Adverse Events assessed by inquiry at month 0
timeFrame: month 0
measure: Adverse Events assessed by inquiry at month 3
timeFrame: month 3
measure: Adverse Events assessed by inquiry at month 6
timeFrame: month 6
measure: Adverse Events assessed by inquiry at month 12
timeFrame: month 12
measure: Adverse Events assessed by inquiry at month 18
timeFrame: month 18
measure: Adverse Events assessed by inquiry at month 24
timeFrame: month 24
measure: ophthalmological examination: Refractive Error, Slit Lamp Exam, Ophthalmoscopy (Vitreous, Retina, Macula, Choroid, Optic Nerve), Intra-Ocular Pressure (IOP) Measurement at month 0
timeFrame: month 0
measure: ophthalmological examination: Refractive Error, Slit Lamp Exam, Ophthalmoscopy (Vitreous, Retina, Macula, Choroid, Optic Nerve), Intra-Ocular Pressure (IOP) Measurement at month 3
timeFrame: month 3
measure: ophthalmological examination: Refractive Error, Slit Lamp Exam, Ophthalmoscopy (Vitreous, Retina, Macula, Choroid, Optic Nerve), Intra-Ocular Pressure (IOP) Measurement at month 6
timeFrame: month 6
measure: ophthalmological examination: Refractive Error, Slit Lamp Exam, Ophthalmoscopy (Vitreous, Retina, Macula, Choroid, Optic Nerve), Intra-Ocular Pressure (IOP) Measurement at month 12
timeFrame: month 12
measure: ophthalmological examination: Refractive Error, Slit Lamp Exam, Ophthalmoscopy (Vitreous, Retina, Macula, Choroid, Optic Nerve), Intra-Ocular Pressure (IOP) Measurement at month 18
timeFrame: month 18
measure: ophthalmological examination: Refractive Error, Slit Lamp Exam, Ophthalmoscopy (Vitreous, Retina, Macula, Choroid, Optic Nerve), Intra-Ocular Pressure (IOP) Measurement at month 24
timeFrame: month 24
Locations:
city: Odense
country: Denmark
facility: Syddansk Universitet (SDU)
city: Paris
country: France
facility: AP - Hopitaux de Paris (AP-HP)
city: Ulm
country: Germany
facility: Universitaet Ulm (UUlm)
city: Milano
country: Italy
facility: Universita Vita-Salute San Raffaele (USR)
city: Padova
country: Italy
facility: Universita degli Study di Padova(UPadova)
city: Coimbra
country: Portugal
facility: Aibili - Cec
city: Barcelona
country: Spain
facility: Institut Catala de la Salut - Hospital Universitari Vall d'Hebron (ICS-HUVH)
city: Cheltenham
country: United Kingdom
facility: Gloucestershire Hospitals NHS Foundation Trust (CHGH)
state: Gloucestershire
city: Birmingham
country: United Kingdom
facility: Aston University (UAston)Heart of England NHS Foundation Trust
city: Liverpool
country: United Kingdom
facility: The University of Liverpool (UOL)
city: London
country: United Kingdom
facility: Moorfields Eye Hospital NHS Foundation Trust (MEH)
Study officials:
affiliation: Association for Innovation and Biomedical Research on Light and Image
name: José Cunha-Vaz, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cunha-Vaz J, Ribeiro L, Costa M, Simo R. Diabetic Retinopathy Phenotypes of Progression to Macular Edema: Pooled Analysis From Independent Longitudinal Studies of up to 2 Years' Duration. Invest Ophthalmol Vis Sci. 2017 May 1;58(6):BIO206-BIO210. doi: 10.1167/iovs.17-21780.
citation: Santos AR, Ribeiro L, Bandello F, Lattanzio R, Egan C, Frydkjaer-Olsen U, Garcia-Arumi J, Gibson J, Grauslund J, Harding SP, Lang GE, Massin P, Midena E, Scanlon P, Aldington SJ, Simao S, Schwartz C, Ponsati B, Porta M, Costa MA, Hernandez C, Cunha-Vaz J, Simo R; European Consortium for the Early Treatment of Diabetic Retinopathy (EUROCONDOR). Functional and Structural Findings of Neurodegeneration in Early Stages of Diabetic Retinopathy: Cross-sectional Analyses of Baseline Data of the EUROCONDOR Project. Diabetes. 2017 Sep;66(9):2503-2510. doi: 10.2337/db16-1453. Epub 2017 Jun 29.