E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of neurodegeneration which occurs in Diabetic Retinopathy |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of neurodegeneration which occurs in Diabetic Retinopathy |
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E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012689 |
E.1.2 | Term | Diabetic retinopathy |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess whether neuroprotective drugs administered topically (somatostatin and brimonidine) are able to prevent or arrest the development and progression of neurodegenerative changes. |
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E.2.2 | Secondary objectives of the trial |
▪To determine the prevalence of functional and structural abnormalities related to neurodegeneration in those patients with or without detectable microvascular damage.
▪To identify those patients most prone to progressive worsening of the retinopathy by identifying progression of DR using the ETDRS severity scale, BCVA, microvascular disease activity (MA turnover and retinal thickness) and neurodegenerative changes.
▪To assess the correlation between the presence and progression of neuronal and glial alterations (mfERG abnormalities and ganglion cell layer thickness) and the appearance and progression of the microvascular lesions (MA turnover and overall retinal thickness).
▪To assess whether there is an effect on the visual-related quality of life in the early stages of nonproliferative DR as measured by the VFQ-25.
▪To evaluate the local and systemic adverse events of the selected drugs. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Changes in the Implicit Time assessed by mfERG (IT-mfERG) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
month 0, month 6, month 12, month 18, month 24 |
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E.5.2 | Secondary end point(s) |
Neurodegenerative variables:
Retinal Nerve Fiber Layer (RNFL) assessed by SD-OCT
Ganglion Cell Layer (GCL) assessed by SD-OCT
Microvascular variables:
Microaneurysm turnover assessed by Colour Fundus Photography
Retinal thickness assessed by SD-OCT
Central retinal thickness assessed by SD-OCT
DR severity assessed by ETDRS scale
Other variables:
BCVA assessed by ETDRS scale
Visual Fields defects assessed by Visual Fields Test
Visual health assessed by Visual Function Questionnaire (VFQ-25)
Adverse Events assessed by inquiry and ophthalmological examination
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-Ophthalmological Examination: Screening, month 0, month 3, month 6, month 12, month 18, month 24
-VFQ-25 and VF:month 0, month 24
-CFP – 30º/35º-7 fields (for ETDRS grading): Screening, month 24
-CFP – 45º/50º Field 2 (for automated MA assessment): Screening, month 6, month 12, month 18, month 24
-SD-OCT, BCVA:month 0, month 6, month 12, month 18, month 24 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
The trial is double blind for somatostatin but open for brimonidine |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 32 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 32 |
E.8.9.2 | In all countries concerned by the trial days | 0 |