Clinical trial NCT02068625: Rasagiline (Azilect) - Neuroprotection for Macula-off Retinal Detachment
Official title: Rasagiline (Azilect) - Neuroprotection for Macula-off Retinal Detachment
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Retinal Detachment
Keywords: retinal detachment
rasagiline
optical coherence tomography
visual acuity
neuroprotection
azilect
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2014-02-21
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: This randomised, double-blind, placebo-controlled clinical trial investigates the neuroprotective effect of rasagiline in patients suffering from a retinal detachment affecting central vision. Based on results from a study in mice suffering from retinal degeneration, the investigators hypothesize that rasagiline delays neurodegeneration in the retina and improves visual acuity outcomes after retinal detachment surgery. Rasagiline is a second-generation propargylamine with neuroprotective properties modulating the caspase-dependent pathway of programmed cell death.

Detailed description: Background

In previous experimental studies neuroprotection by rasagiline has been shown in rds-mice, a model for slow retinal degeneration. It is known from these experiments that rasagiline specifically delays apoptosis, but also modifies inflammation and autophagy. The bioavailability of the drug in the central nervous system is high, and based on the literature is sufficient in the retina.

In retinal detachments the outer layers of the neurosensory retina are deprived of nutrients and degeneration of the photoreceptors occurs fast. This is particularly relevant in the macular area of the retina where the density of photoreceptors is high, such that visual acuity recovery can be significantly limited by photoreceptor loss.

Objective

To assess the neuroprotective effect of oral rasagiline (1mg daily for 7 days) administered perioperatively in patients undergoing surgical retinal detachment repair for central vision involving retinal detachments.

Methods

In this clinical trial, patients suffering from retinal detachments affecting the fovea get randomly assigned to perioperative oral treatment with either rasagiline (1mg) or placebo once daily for 7 days. Pharmacologic treatment is initiated at the time of hospital admission, usually the day before surgery. The main outcome of the study is visual acuity six months after surgical retinal detachment repair. Structural differences of the neurosensory retina between groups will be analysed by optical coherence tomography, a non-invasive imaging method for retinal pathology.

Eligibility criteria: Inclusion Criteria:

* Rhegmatogenous retinal detachment
* Central vision affected for less than 72 hours
* Pseudophakic
* Age 18 or over
* Not participating in other clinical trials
* Willing to attend follow-up visits
* Written informed consent

Exclusion Criteria

* Phakic
* Narrow angle glaucoma
* Previous intraocular surgery other than cataract operation
* Retinal disease
* Concurrent treatment with MAO inhibitors
* Pregnancy
* Malignant arterial hypertension
* Liver or kidney failure
* Life-threatening or malignant disease

Primary outcomes:
measure: ETDRS Visual Acuity
timeFrame: 6 months
Secondary outcomes:
measure: Central retinal thickness
timeFrame: 6 months
measure: Number of patients with side effects
timeFrame: 6 months
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: Department of Ophthalmology, Bern University Hospital
Study officials:
affiliation: Department of Ophthalmology, Bern University Hospital
name: Sebastian Wolf
role: STUDY_CHAIR
affiliation: Department of Ophthalmology, Bern University Hospital
name: Andreas Ebneter
role: PRINCIPAL_INVESTIGATOR
References:
citation: Eigeldinger-Berthou S, Meier C, Zulliger R, Lecaude S, Enzmann V, Sarra GM. Rasagiline interferes with neurodegeneration in the Prph2/rds mouse. Retina. 2012 Mar;32(3):617-28. doi: 10.1097/IAE.0b013e31821e2070.
citation: Youdim MB, Bar Am O, Yogev-Falach M, Weinreb O, Maruyama W, Naoi M, Amit T. Rasagiline: neurodegeneration, neuroprotection, and mitochondrial permeability transition. J Neurosci Res. 2005 Jan 1-15;79(1-2):172-9. doi: 10.1002/jnr.20350.
citation: Travis GH. Mechanisms of cell death in the inherited retinal degenerations. Am J Hum Genet. 1998 Mar;62(3):503-8. doi: 10.1086/301772. No abstract available.
citation: Cook B, Lewis GP, Fisher SK, Adler R. Apoptotic photoreceptor degeneration in experimental retinal detachment. Invest Ophthalmol Vis Sci. 1995 May;36(6):990-6.
citation: Eliash S, Shteter N, Eilam R. Neuroprotective effect of rasagiline, a monoamine oxidase-B inhibitor, on spontaneous cell degeneration in a rat model. J Neural Transm (Vienna). 2005 Aug;112(8):991-1003. doi: 10.1007/s00702-004-0254-4. Epub 2005 Mar 15.