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
  Purpose

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.


Condition
Alzheimer Disease
Oxidative Stress
Adrenocortical Hyperfunction

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Isolated Erythrocyte Membrane Susceptibility to Photo-oxidative Stress in Patients Affected by Alzheimer's Disease and Healthy Controls

Resource links provided by NLM:


Further study details as provided by Campus Bio-Medico University:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Biospecimen Retention:   Samples With DNA
Whole blood

Estimated Enrollment: 50
Study Start Date: June 2015
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
Alzheimer's disease
Non demented subjects

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.

  Eligibility

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

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.
  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: NCT01707719

Contacts
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

Locations
Italy
Policlinico Universitario Campus Bio-Medico Recruiting
Rome, RM, Italy, 00128
Contact: Raffaele Antonelli Incalzi, M.D.    +39-06-225411    r.antonelli@unicampus.it   
Contact: Francesco Maria Serino, M.D.    +39-06-225411 ext 9123    info@doctorsinitaly.com   
Sponsors and Collaborators
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
  More Information

Publications:

Responsible Party: Raffaele Antonelli Incalzi, Professor, Campus Bio-Medico University
ClinicalTrials.gov Identifier: NCT01707719     History of Changes
Other Study ID Numbers: ERASE 
Study First Received: October 1, 2012
Last Updated: March 31, 2016
Health Authority: Italy: National Institute of Health

Keywords provided by Campus Bio-Medico University:
Alzheimer's disease
Oxidative stress
HPA axis

Additional relevant MeSH terms:
Alzheimer Disease
Adrenocortical Hyperfunction
Disease Susceptibility
Adrenal Gland Diseases
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Disease Attributes
Endocrine System Diseases
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Pathologic Processes
Tauopathies

ClinicalTrials.gov processed this record on April 27, 2016