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

NCT ID: NCT01707719

Last Updated: 2020-01-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

48 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-06-30

Study Completion Date

2018-11-30

Brief Summary

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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

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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.

Conditions

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Alzheimer Disease Oxidative Stress Adrenocortical Hyperfunction

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Alzheimer's disease

No interventions assigned to this group

Non demented subjects

No interventions assigned to this group

Eligibility Criteria

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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.
Minimum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Raffaele Antonelli Incalzi

OTHER

Sponsor Role lead

Responsible Party

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Raffaele Antonelli Incalzi

Professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Francesco Maria Serino, M.D. PhD

Role: PRINCIPAL_INVESTIGATOR

Doctors in Italy

Chiara Fanali, PhD

Role: PRINCIPAL_INVESTIGATOR

University Campus Bio-Medico

Laura Dugo, PhD

Role: PRINCIPAL_INVESTIGATOR

University Campus Bio-Medico

Simone Grasso, PhD

Role: PRINCIPAL_INVESTIGATOR

University Campus Bio-Medico

Ettore Bergamini, M.D.

Role: STUDY_CHAIR

University of Pisa

Francesca Ursini, M.D.

Role: PRINCIPAL_INVESTIGATOR

University Campus Bio-Medico

Fabrizio Vernieri, M.D.

Role: PRINCIPAL_INVESTIGATOR

University Campus Bio-Medico

Marina Dachà, BS.Pharm

Role: STUDY_DIRECTOR

University Campus Bio-Medico

Silvia Bernardini, M.D.

Role: PRINCIPAL_INVESTIGATOR

University Campus Bio-Medico

Valentina Pasqualetti, PhD

Role: PRINCIPAL_INVESTIGATOR

University Campus Bio-Medico

Locations

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Policlinico Universitario Campus Bio-Medico

Rome, RM, Italy

Site Status

Countries

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Italy

References

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Mangialasche F, Polidori MC, Monastero R, Ercolani S, Camarda C, Cecchetti R, Mecocci P. Biomarkers of oxidative and nitrosative damage in Alzheimer's disease and mild cognitive impairment. Ageing Res Rev. 2009 Oct;8(4):285-305. doi: 10.1016/j.arr.2009.04.002. Epub 2009 Apr 17.

Reference Type BACKGROUND
PMID: 19376275 (View on PubMed)

Markesbery WR. Oxidative stress hypothesis in Alzheimer's disease. Free Radic Biol Med. 1997;23(1):134-47. doi: 10.1016/s0891-5849(96)00629-6.

Reference Type BACKGROUND
PMID: 9165306 (View on PubMed)

Perry G, Nunomura A, Hirai K, Zhu X, Perez M, Avila J, Castellani RJ, Atwood CS, Aliev G, Sayre LM, Takeda A, Smith MA. Is oxidative damage the fundamental pathogenic mechanism of Alzheimer's and other neurodegenerative diseases? Free Radic Biol Med. 2002 Dec 1;33(11):1475-9. doi: 10.1016/s0891-5849(02)01113-9.

Reference Type BACKGROUND
PMID: 12446204 (View on PubMed)

Mecocci P. Oxidative stress in mild cognitive impairment and Alzheimer disease: a continuum. J Alzheimers Dis. 2004 Apr;6(2):159-63. doi: 10.3233/jad-2004-6207.

Reference Type BACKGROUND
PMID: 15096699 (View on PubMed)

Polidori MC, Mecocci P. Plasma susceptibility to free radical-induced antioxidant consumption and lipid peroxidation is increased in very old subjects with Alzheimer disease. J Alzheimers Dis. 2002 Dec;4(6):517-22. doi: 10.3233/jad-2002-4608.

Reference Type BACKGROUND
PMID: 12629261 (View on PubMed)

Galbusera C, Facheris M, Magni F, Galimberti G, Sala G, Tremolada L, Isella V, Guerini FR, Appollonio I, Galli-Kienle M, Ferrarese C. Increased susceptibility to plasma lipid peroxidation in Alzheimer disease patients. Curr Alzheimer Res. 2004 May;1(2):103-9. doi: 10.2174/1567205043332171.

Reference Type BACKGROUND
PMID: 15975074 (View on PubMed)

Casado A, Encarnacion Lopez-Fernandez M, Concepcion Casado M, de La Torre R. Lipid peroxidation and antioxidant enzyme activities in vascular and Alzheimer dementias. Neurochem Res. 2008 Mar;33(3):450-8. doi: 10.1007/s11064-007-9453-3. Epub 2007 Aug 25.

Reference Type BACKGROUND
PMID: 17721818 (View on PubMed)

Serra JA, Dominguez RO, de Lustig ES, Guareschi EM, Famulari AL, Bartolome EL, Marschoff ER. Parkinson's disease is associated with oxidative stress: comparison of peripheral antioxidant profiles in living Parkinson's, Alzheimer's and vascular dementia patients. J Neural Transm (Vienna). 2001;108(10):1135-48. doi: 10.1007/s007020170003.

Reference Type BACKGROUND
PMID: 11725816 (View on PubMed)

Kawamoto EM, Munhoz CD, Glezer I, Bahia VS, Caramelli P, Nitrini R, Gorjao R, Curi R, Scavone C, Marcourakis T. Oxidative state in platelets and erythrocytes in aging and Alzheimer's disease. Neurobiol Aging. 2005 Jun;26(6):857-64. doi: 10.1016/j.neurobiolaging.2004.08.011.

Reference Type BACKGROUND
PMID: 15718044 (View on PubMed)

Bermejo P, Gomez-Serranillos P, Santos J, Pastor E, Gil P, Martin-Aragon S. Determination of malonaldehyde in Alzheimer's disease: a comparative study of high-performance liquid chromatography and thiobarbituric acid test. Gerontology. 1997;43(4):218-22. doi: 10.1159/000213853.

Reference Type BACKGROUND
PMID: 9222750 (View on PubMed)

Baldeiras I, Santana I, Proenca MT, Garrucho MH, Pascoal R, Rodrigues A, Duro D, Oliveira CR. Peripheral oxidative damage in mild cognitive impairment and mild Alzheimer's disease. J Alzheimers Dis. 2008 Sep;15(1):117-28. doi: 10.3233/jad-2008-15110.

Reference Type BACKGROUND
PMID: 18780972 (View on PubMed)

Torres LL, Quaglio NB, de Souza GT, Garcia RT, Dati LM, Moreira WL, Loureiro AP, de Souza-Talarico JN, Smid J, Porto CS, Bottino CM, Nitrini R, Barros SB, Camarini R, Marcourakis T. Peripheral oxidative stress biomarkers in mild cognitive impairment and Alzheimer's disease. J Alzheimers Dis. 2011;26(1):59-68. doi: 10.3233/JAD-2011-110284.

Reference Type BACKGROUND
PMID: 21593563 (View on PubMed)

Onaran I, Yalcin AS, Sultuybek G. Effect of donor age on the susceptibility of erythrocytes and erythrocyte membranes to cumene hydroperoxide-induced oxidative stress. Mech Ageing Dev. 1997 Nov;98(2):127-38. doi: 10.1016/s0047-6374(97)00078-x.

Reference Type BACKGROUND
PMID: 9379709 (View on PubMed)

Garcia-Arumi E, Andreu AL, Lopez-Hellin J, Schwartz S. Effect of oxidative stress on lymphocytes from elderly subjects. Clin Sci (Lond). 1998 Apr;94(4):447-52. doi: 10.1042/cs0940447.

Reference Type BACKGROUND
PMID: 9640351 (View on PubMed)

Davis KL, Davis BM, Greenwald BS, Mohs RC, Mathe AA, Johns CA, Horvath TB. Cortisol and Alzheimer's disease, I: Basal studies. Am J Psychiatry. 1986 Mar;143(3):300-5. doi: 10.1176/ajp.143.3.300.

Reference Type BACKGROUND
PMID: 3953862 (View on PubMed)

Costantini D, Marasco V, Moller AP. A meta-analysis of glucocorticoids as modulators of oxidative stress in vertebrates. J Comp Physiol B. 2011 May;181(4):447-56. doi: 10.1007/s00360-011-0566-2. Epub 2011 Mar 18.

Reference Type BACKGROUND
PMID: 21416253 (View on PubMed)

Joergensen A, Broedbaek K, Weimann A, Semba RD, Ferrucci L, Joergensen MB, Poulsen HE. Association between urinary excretion of cortisol and markers of oxidatively damaged DNA and RNA in humans. PLoS One. 2011;6(6):e20795. doi: 10.1371/journal.pone.0020795. Epub 2011 Jun 7.

Reference Type BACKGROUND
PMID: 21687734 (View on PubMed)

Other Identifiers

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ERASE

Identifier Type: -

Identifier Source: org_study_id

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