Clinical trial NCT01707719: Isolated Erythrocyte Membrane Susceptibility to Photo-oxidative Stress in Alzheimer's Disease
Official title: Isolated Erythrocyte Membrane Susceptibility to Photo-oxidative Stress in Patients Affected by Alzheimer's Disease and Healthy Controls
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Alzheimer Disease
Oxidative Stress
Adrenocortical Hyperfunction
Keywords: Alzheimer's disease
Oxidative stress
HPA axis
Lead sponsor: Campus Bio-Medico University
Sponsor class: OTHER
First posted: 2012-10-16
Enrollment: 48
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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

Brief summary: 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.

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 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.

Primary outcomes:
measure: Malondialdehyde assay
timeFrame: At the time of recruitment
Secondary outcomes:
measure: Relationship between urinary excretion of cortisol and levels of malondialdehyde
timeFrame: At the time of recruitment
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Policlinico Universitario Campus Bio-Medico
state: RM
Study officials:
affiliation: Doctors in Italy
name: Francesco Maria Serino, M.D. PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Campus Bio-Medico
name: Chiara Fanali, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Campus Bio-Medico
name: Laura Dugo, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Campus Bio-Medico
name: Simone Grasso, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pisa
name: Ettore Bergamini, M.D.
role: STUDY_CHAIR
affiliation: University Campus Bio-Medico
name: Francesca Ursini, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University Campus Bio-Medico
name: Fabrizio Vernieri, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University Campus Bio-Medico
name: Marina Dachà, BS.Pharm
role: STUDY_DIRECTOR
affiliation: University Campus Bio-Medico
name: Silvia Bernardini, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University Campus Bio-Medico
name: Valentina Pasqualetti, PhD
role: PRINCIPAL_INVESTIGATOR
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