Isolated Erythrocyte Membrane Susceptibility to Photo-oxidative Stress in Alzheimer's Disease

January 22, 2020 updated by: Raffaele Antonelli Incalzi

Isolated Erythrocyte Membrane Susceptibility to Photo-oxidative Stress in Patients Affected by Alzheimer's Disease and Healthy Controls

High lipid peroxidation and altered antioxidant defenses have been frequently reported in Alzheimer's disease patients.

The purpose of this study is to investigate susceptibility to photo-oxidation of isolated erythrocyte membranes, in patients affected by Alzheimer's disease and age- and sex-matched, non demented subjects.

Study Overview

Status

Completed

Conditions

Detailed Description

The study hypothesis is that high lipid peroxidation and decreased antioxidant defenses characterize the natural history of Alzheimer's disease.

It will be evaluated the release of malondialdehyde (MDA) from ex-vivo photo-oxidized erythrocyte ghosts, through a very easy and convenient lab procedure for the preparation of erythrocyte membrane samples.

Isolated and purified red blood cell membranes will be in vitro exposed to oxidative stress by UV-B radiation. The extent of cell membrane damage will be quantified by the fluorometric determination of MDA.

Induction of oxidative stress through ultraviolet rays, unlike that obtained by chemical oxidizing agents, is fully controllable, since it produces effects only during irradiation. Moreover, using isolated erythrocyte membranes allows for a greater specificity in the evaluation of MDA produced, and reduces the amount of blood required for the assay.

A portion of the blood sample (500 µL) will be sent to the laboratory of Lipinutragen (spin-off of CNR- National Research Center Bologna, Italy) where an erythrocyte membrane lipidomic analysis will be performed for the characterization of membrane phospholipids, in order to determinate the different lipid components (saturated fatty acids, monounsaturated and polyunsaturated, trans fatty acids), each one characterized by a different oxidative reactivity.

Recently published papers showed a striking association between urinary excretion of cortisol and the increase of some markers of oxidative damage of DNA and RNA (in humans). This finding provides further support to the idea that chronic psychological stress, who is associated to hypercortisolemia, can lead to an acceleration of the aging process.

The brain is a major target of the effects of glucocorticoids (CCS). The harmful consequences of cortisol on the hippocampus (one of the first brain areas affected by Alzheimer's disease) are well known. Some studies showed inverse correlations between cortisol levels and neuropsychological performance in patients with depression, dementia as well as in people treated chronically with CCS.

Alzheimer's disease is associated with states of hypercortisolism. Nonetheless, so far, its correlation with the level of oxidative stress has not been studied. We will investigate the relationship between 24h excretion of urinary cortisol and the level of malondialdehyde, produced by isolated and purified red blood cell membranes, in vitro exposed to oxidative stress by UV-B radiation.

Study Type

Observational

Enrollment (Actual)

48

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • RM
      • Rome, RM, Italy, 00128
        • Policlinico Universitario Campus Bio-Medico

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patients meeting NINCDS-ADRDA criteria for Alzheimer's disease and age- / sex-matched elderly subjects without dementia, will be recruited from those referring neurologists or geriatricians on an outpatient basis

Description

Inclusion Criteria:

  • Outpatients of both sexes diagnosed with Alzheimer's disease according to NINCDS-ADRDA criteria.
  • Age and sex-matched elderly subjects without dementia.

Exclusion Criteria:

  • Recent neoplasia (< 1 year)
  • Vitamin B12 deficiency, positive serology for syphilis, thyroid function abnormalities considered to be significant by the care provider.
  • Use of vitamin or mineral supplements.
  • Diagnosis of malnutrition (based on body mass index and total protein levels)
  • Metabolic syndrome or diabetes.
  • Hormonal replacement therapy.
  • Smoking
  • Chronic inflammatory disease (e.g. rheumatoid arthritis) and any other acute illness.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Alzheimer's disease
Non demented subjects

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Malondialdehyde assay
Time Frame: At the time of recruitment
Isolated and purified red blood cell membranes will be in vitro exposed to oxidative stress by UV-B radiation. The extent of cell membrane damage will be quantified by the fluorometric determination of malondialdehyde.
At the time of recruitment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relationship between urinary excretion of cortisol and levels of malondialdehyde
Time Frame: At the time of recruitment
Hyperactivity of the hypothalamic pituitary adrenal axis has been frequently described in Alzheimer's disease. Recently published work reported an association between high secretion of cortisol and oxidative stress. We will investigate the relationship between 24 h excretion of urinary cortisol and the level of malondialdehyde, produced by isolated and purified red blood cell membranes, in vitro exposed to oxidative stress by UV-B radiation.
At the time of recruitment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Raffaele Antonelli Incalzi

Investigators

  • Principal Investigator: Francesco Maria Serino, M.D. PhD, Doctors in Italy
  • Principal Investigator: Chiara Fanali, PhD, University Campus Bio-Medico
  • Principal Investigator: Laura Dugo, PhD, University Campus Bio-Medico
  • Principal Investigator: Simone Grasso, PhD, University Campus Bio-Medico
  • Study Chair: Ettore Bergamini, M.D., University of Pisa
  • Principal Investigator: Francesca Ursini, M.D., University Campus Bio-Medico
  • Principal Investigator: Fabrizio Vernieri, M.D., University Campus Bio-Medico
  • Study Director: Marina Dachà, BS.Pharm, University Campus Bio-Medico
  • Principal Investigator: Silvia Bernardini, M.D., University Campus Bio-Medico
  • Principal Investigator: Valentina Pasqualetti, PhD, University Campus Bio-Medico

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2015

Primary Completion (Actual)

November 1, 2018

Study Completion (Actual)

November 1, 2018

Study Registration Dates

First Submitted

October 1, 2012

First Submitted That Met QC Criteria

October 15, 2012

First Posted (Estimate)

October 16, 2012

Study Record Updates

Last Update Posted (Actual)

January 23, 2020

Last Update Submitted That Met QC Criteria

January 22, 2020

Last Verified

March 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ERASE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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