Retinal Neurodegenerative Signs in Alzheimer's Diseases (SIGNAL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University Hospital, Bordeaux
Sponsor:
Information provided by (Responsible Party):
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT01555827
First received: March 14, 2012
Last updated: May 9, 2014
Last verified: May 2014
  Purpose

A few studies suggest that patients suffering from neurodegenerative diseases (such a multiple sclerosis or Alzheimer's disease (AD)) show decreased thickness of the retinal nerve fiber layer (RNFL), indicating axonal degeneration. High-definition spectral domain optical coherence tomography (SD-OCT), performed without radiation in a few seconds per eye, offers a precise and standardized estimation of this parameter, which could constitute a biomarker for cerebral axonal degeneration. These RNFL deficits might even be the earliest sign of AD, prior to damage of the hippocampal region that impacts memory.

Besides, some associations of AD with some degenerative diseases of the eye (glaucoma, microvascular abnormalities, age-related macular degeneration (AMD)) have also been reported.

It therefore seems interesting to determine whether RNFL thickness, and other ocular parameters, may give some indications for a better detection of AD and cognitive decline in the elderly.


Condition Intervention
Alzheimer's Disease
Other: Ophthalmological examination & Questionnaire

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Retinal Neurodegenerative Signs in Alzheimer's Diseases

Resource links provided by NLM:


Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:
  • RNFL thickness measured on a peri-papillary scan of SD-OCT examination. [ Time Frame: inclusion visit (day0) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Glaucomatous optic nerve damage observed on colour photographs (cup/disc ratio) [ Time Frame: inclusion visit (day0) ] [ Designated as safety issue: No ]
  • Retinal microvascular abnormalities (microaneurysms, micro-hemorrhage, cotton wool spots, arteriovenous nicking), observed on retinal colour photography [ Time Frame: inclusion visit (day0) ] [ Designated as safety issue: No ]
  • Macular abnormalities observed on retinal colour photographs (drusen, pigmentary abnormalities, neovascular AMD, atrophic AMD, other retinal diseases) [ Time Frame: inclusion visit (day0) ] [ Designated as safety issue: No ]
  • Macular abnormalities observed on macular scans in SD-OCT (drusen, pigmentary abnormalities, neovascular AMD, atrophic AMD, epiretinal membranes, other retinal diseases). [ Time Frame: inclusion visit (day0) ] [ Designated as safety issue: No ]
  • Macular abnormalities observed in autofluorescence imaging (increased autofluorescence, decreased autofluorescence, reticular drusen, atrophic AMD, other abnormalities) [ Time Frame: inclusion visit (day0) ] [ Designated as safety issue: No ]
  • Macular and peripheral abnormalities diagnosed in wide-field retinal imaging [ Time Frame: inclusion visit (day0) ] [ Designated as safety issue: No ]
  • Retinal blood flow velocity (RFI) [ Time Frame: inclusion visit (day0) ] [ Designated as safety issue: No ]
  • Intraocular pressure [ Time Frame: inclusion visit (day0) ] [ Designated as safety issue: No ]
  • axial length [ Time Frame: inclusion visit (day 0) ] [ Designated as safety issue: No ]

Estimated Enrollment: 450
Study Start Date: April 2012
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alzheimer Disease Other: Ophthalmological examination & Questionnaire

The following examinations will be performed, after pupil dilation:

  • Examination with SD-OCT (macular scans, macular volume, peri-papillary scan, retinal autofluorescence, infer-red and red-free imaging)
  • Colour photographs of the retinal, centered on the macula and on the optic nerve (digital non mydriatic retinal camera)
  • Wide-field colour and autofluorescence imaging (Optomap)
  • Measure of intra-ocular pressure (pneumotonometer)

The following informations will be collected through a standardized questionnaire, administered face-to-face during the inclusion visit, or at the moment of the verification of eligibility criteria:

  • Age, gender
  • educational level
  • smoking
  • cardiovascular diseases, current medications
  • scores at neuropsychological tests
Active Comparator: amnestic MCI Other: Ophthalmological examination & Questionnaire

The following examinations will be performed, after pupil dilation:

  • Examination with SD-OCT (macular scans, macular volume, peri-papillary scan, retinal autofluorescence, infer-red and red-free imaging)
  • Colour photographs of the retinal, centered on the macula and on the optic nerve (digital non mydriatic retinal camera)
  • Wide-field colour and autofluorescence imaging (Optomap)
  • Measure of intra-ocular pressure (pneumotonometer)

The following informations will be collected through a standardized questionnaire, administered face-to-face during the inclusion visit, or at the moment of the verification of eligibility criteria:

  • Age, gender
  • educational level
  • smoking
  • cardiovascular diseases, current medications
  • scores at neuropsychological tests
Active Comparator: Control Other: Ophthalmological examination & Questionnaire

The following examinations will be performed, after pupil dilation:

  • Examination with SD-OCT (macular scans, macular volume, peri-papillary scan, retinal autofluorescence, infer-red and red-free imaging)
  • Colour photographs of the retinal, centered on the macula and on the optic nerve (digital non mydriatic retinal camera)
  • Wide-field colour and autofluorescence imaging (Optomap)
  • Measure of intra-ocular pressure (pneumotonometer)

The following informations will be collected through a standardized questionnaire, administered face-to-face during the inclusion visit, or at the moment of the verification of eligibility criteria:

  • Age, gender
  • educational level
  • smoking
  • cardiovascular diseases, current medications
  • scores at neuropsychological tests

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Inclusion criteria for AD cases:
  • Diagnosis of probable AD, defined according to the NINCDS-ARDRA criteria51
  • Light to moderate severity of the disease, defined by a MMSE score >10 (global evaluation of cognition)
  • Patient aged 50 years or more
  • Patient benefiting from social insurance

Inclusion criteria for cases of amnestic "MCI":

  • Patient with cognitive complaint
  • Not demented with Clinical Dementia Rating ≤ 0.5
  • Free recall <17 or total recall <40 for the Free and Cued Selective Reminding - Test (Grober and Buschke test 52)
  • Normal or slightly affected Instrumental Activities of Daily Living (at most first grade alterations)
  • Patient aged 50 years or more
  • Patient benefiting from social insurance

Inclusion criteria for controls:

  • Absence of suspicion of dementia, based on normal performance according to age and educational level at neuropsychological testing defined as:
  • Free recall ≥17 and total recall ≥40 for the Free and Cued Selective Reminding Test (Grober and Buschke test 52) MMSE ≥ norm for age and educational level (defined by mean - 1 SD)
  • Isaac's set test ≥ norm for age and educational level (defined by mean - 1 SD)
  • Matched to age and gender of the cases
  • Patient benefiting from social insurance

Exclusion Criteria:

Exclusion criteria for all patients :

  • History of Parkinson's disease or other neurodegenerative disorder
  • History of Horton's disease
  • History of inflammatory neuropathies (in particular Devic's disease, multiple sclerosis)
  • History of vascular ischemic neuropathies and chronic intracranial hypertension
  • History of pituitary tumors
  • Presence of diseases (systemic and/or ocular diseases) or behavioural or cognitive symptoms incompatible with eye examination
  • Known diabetes
  • Person under tutorship or curatorship, person unable to express consent

Additional exclusion criteria for AD and amnestic MCI cases:

  • Dementia of other cause than AD
  • Severe AD, defined by MMSE score ≤ 10

Additional exclusion criteria for controls:

  • Presence of dementia, of whatever cause
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01555827

Contacts
Contact: Jean-François KOROBELNIK, Pr jean-françois.korobelnik@chu-bordeaux.fr

Locations
France
CHU Bordeaux - hôpital Pellegrin Recruiting
Bordeaux, France, 33000
Principal Investigator: Jean-François KOROBELNIK, Pr         
Sponsors and Collaborators
University Hospital, Bordeaux
Investigators
Principal Investigator: Jean-François KOROBELNIK, Pr University Hospital, Bordeaux, France
Study Chair: Delcourt Cécile, Dr ISPED, bordeaux, France
  More Information

No publications provided

Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT01555827     History of Changes
Other Study ID Numbers: CHUBX2011/19
Study First Received: March 14, 2012
Last Updated: May 9, 2014
Health Authority: France: Ministry of Health

Keywords provided by University Hospital, Bordeaux:
Retina
ALzheimer's disease
neurodegenerative signs

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies

ClinicalTrials.gov processed this record on October 30, 2014