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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2016 by Campus Bio-Medico University
Sponsor:
Information provided by (Responsible Party):
Raffaele Antonelli Incalzi, Campus Bio-Medico University
ClinicalTrials.gov Identifier:
NCT01707719
First received: October 1, 2012
Last updated: March 31, 2016
Last verified: March 2016

October 1, 2012
March 31, 2016
June 2015
September 2016   (final data collection date for primary outcome measure)
Malondialdehyde assay [ Time Frame: At the time of recruitment ] [ Designated as safety issue: No ]
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.
Same as current
Complete list of historical versions of study NCT01707719 on ClinicalTrials.gov Archive Site
Relationship between urinary excretion of cortisol and levels of malondialdehyde [ Time Frame: At the time of recruitment ] [ Designated as safety issue: No ]
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.
Same as current
Not Provided
Not Provided
 
Isolated Erythrocyte Membrane Susceptibility to Photo-oxidative Stress in Alzheimer's Disease
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.

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.

Observational
Observational Model: Case Control
Time Perspective: Cross-Sectional
Not Provided
Retention:   Samples With DNA
Description:
Whole blood
Probability Sample
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
  • Alzheimer Disease
  • Oxidative Stress
  • Adrenocortical Hyperfunction
Not Provided
  • Alzheimer's disease
  • Non demented subjects

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
50
January 2017
September 2016   (final data collection date for primary outcome measure)

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.
Both
50 Years and older   (Adult, Senior)
Yes
Contact: Raffaele Antonelli Incalzi, M.D. +39-06-225411 r.antonelli@unicampus.it
Contact: Francesco Maria Serino, M.D. +39-06-6790695 info@doctorsinitaly.com
Italy
 
NCT01707719
ERASE
Yes
No
Not Provided
Raffaele Antonelli Incalzi, Campus Bio-Medico University
Raffaele Antonelli Incalzi
Not Provided
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
Campus Bio-Medico University
March 2016

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