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Retinal Neurodegeneration in Type 2 Diabetes as Biomarker for Alzheimer´s Disease (DIALRET)

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ClinicalTrials.gov Identifier: NCT02360527
Recruitment Status : Completed
First Posted : February 10, 2015
Last Update Posted : April 12, 2017
Sponsor:
Information provided by (Responsible Party):
Hospital Universitari Vall d'Hebron Research Institute

Brief Summary:
A clear association between type 2 diabetes (T2D) and Alzheimer's disease (AD) has been reported. This association is independent of vascular impairment, and therefore, it could be attributed to neurodegeneration triggered or accelerated by diabetes itself. At present there are no methods to identify T2D patients at risk for developing AD. The retina shares many features with the brain and, therefore, has been suggested as an easily accessible way of examining pathology in the brain. In fact, many patients with AD present retinal abnormalities. However, the diagnosis of diabetes, a condition frequently associated with retinal neurodegeneration, has not been considered. On this basis, the final aim of this proposal is to identify diabetic patients at risk for developing AD based on the assessment of retinal neurodegeneration by means of non-invasive tests. Specific aims: 1) To compare the prevalence of morphological and functional abnormalities related to retinal neurodegeneration among three groups of T2D patients: patients with AD, patients with Mild Cognitive Impairment (MCI) and patients without AD or MCI. 2) To assess whether the retinal neurodegenerative features are related to severity of AD. 3) To explore whether the combined retinal neurodegeneration in diabetic patients with AD has a different functional and/or morphological pattern in comparison with neurodegeneration secondary to diabetes alone. Methods: Case-control study. Retinal neurodegeneration will be assessed by mutifocal electroretinogram (mfERG) and spectral domain optical coherence tomography (SD-OCT). The potential confounders will be considered in data analyses. Feasibility: A unique multidisciplinary consortium has been created in order to warrant the feasibility of the project Expected impact: This innovative approach will fill a gap that currently exist in the health care system and will reduce the economic burden associated with T2D patients with AD. In addition, this project would be the backbone for future prospective studies.

Condition or disease
Retinal Neurodegeneration Alzheimer´s Disease Type 2 Diabetes

Detailed Description:

A case control study in the recruitment will be carried out from the Diabetes outpatient clinic of a tertiary hospital (HUVH) and from the ACE Foundation. The investigators will include the following groups: 1) Type 2 diabetic patients with AD; B) Type 2 diabetic patients with MCI; 3) Type 2 diabetic patients with normal cognitive status; 4) Non-diabetic patients with AD. The groups will be matched by age (± 5 years), gender, risk factors related to AD (APOE genotype and family history of dementia), diabetes duration and Hba1c (±1%)- the last two criteria apply for the three groups of diabetic patients. Inclusion criteria: Written informed consent obtained from the patient; Age >65years; Diabetes duration>5 years; HbA1c < 10%; No apparent or mild non-proliferative DR according to the International Clinical Diabetic Retinopathy Disease Severity Scale. Exclusion criteria: Patients with other neurodegenerative diseases of the brain or retina (i.e. glaucoma) or cerebrovascular diseases. Sample size calculation: Assuming that diabetic patients will present around 30% of abnormal mfERG implicit time, and considering that this figure will be up 60% in those diabetic patients with AD, the number of patients required in each group would be 25. This calculation has been performed taking into account a 2-side risk level of 0.05 and a statistical power of 80%. However, it should be noted that this estimation has been performed taken into account the variables concerning AD. Therefore, it is foreseeable that more patients will be needed to obtain valid results for MCI. Consequently, the investigators feel it reasonable to extend the sample to 35 subjects per group.

The study will be divided into two stages (as will be further detailed): -Stage I: This will be the first step of the project and type 2 diabetic patients with AD and patients with normal cognitive status will be compared. -Stage II: Type 2 diabetic patients with MCI will be compared with patients with normal cognitive status or AD.


Study Type : Observational [Patient Registry]
Actual Enrollment : 126 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Target Follow-Up Duration: 12 Months
Official Title: Retinal Neurodegeneration in Type 2 Diabetes as Biomarker for Alzheimer´s Disease
Actual Study Start Date : September 2014
Actual Primary Completion Date : November 2015
Actual Study Completion Date : December 2015


Group/Cohort
Type 2 diabetic patients with AD
35 patients
Type 2 diabetic patients with MCI
35 patients
Type 2 diabetic patients controls
35 patients
Non-diabetic patients with AD
35 patients



Primary Outcome Measures :
  1. Retinal neurodegeneration among three groups of type 2 diabetic patients patients with AD, patients with MCI and patients without AD or MCI. [ Time Frame: 9 month ]

    -To compare the prevalence of morphological (SD-OCT) and functional abnormalities (mfERG) related to retinal neurodegeneration among three groups of type 2 diabetic patients: patients with AD, patients with MCI and patients without AD or MCI. In addition, a group of non diabetic subjects with AD will also be included.

    These groups will be matched by age, gender, duration of diabetes, HbA1C, and genetic risk factors for AD.

    • To assess whether the retinal neurodegenerative features are related to the severity of AD.
    • To explore whether the combined retinal neurodegeneration in diabetic patients with AD has a different functional and/or morphological pattern in comparison with neurodegeneration secondary to diabetes alone.


Biospecimen Retention:   Samples With DNA
Biochemical evaluation including Hba1c, lipidic profile, renal and hepatic function. We will also determine the APOE genotype and plasmatic beta-amyloidal fractions (Aβ1-40 and Aβ1-42) as previously described (Hixson JE and Vernier DT. Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res 1990;31:545-8.)


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Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
We will include the following groups: 1) Type 2 diabetic patients with AD; B) Type 2 diabetic patients with MCI; 3) Type 2 diabetic patients with normal cognitive status; 4) Non-diabetic patients with AD. The groups will be matched by age (± 5 years), gender, risk factors related to AD (APOE genotype and family history of dementia), diabetes duration and Hba1c (±1%)- the last two criteria apply for the three groups of diabetic patients.
Criteria

Inclusion Criteria:

  • Written informed consent obtained from the patient; Age >65years; Diabetes duration>5 years; HbA1c < 10%; No apparent or mild non-proliferative DR according to the International Clinical Diabetic Retinopathy Disease Severity Scale

Exclusion Criteria:

  • Patients with other neurodegenerative diseases of the brain or retina (i.e. glaucoma) or cerebrovascular diseases.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02360527


Locations
Spain
Vall d´Hebron Research Institute VHIR
Barcelona, Catalunya, Spain, 08035
Sponsors and Collaborators
Hospital Universitari Vall d'Hebron Research Institute
Investigators
Principal Investigator: Cristina Hernandez, MD, PhD Vall d´Hebron Research Institute VHIR

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hospital Universitari Vall d'Hebron Research Institute
ClinicalTrials.gov Identifier: NCT02360527     History of Changes
Other Study ID Numbers: PR(IR)15/2014
First Posted: February 10, 2015    Key Record Dates
Last Update Posted: April 12, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Alzheimer Disease
Nerve Degeneration
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Pathologic Processes