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

Purpose

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

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.

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

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

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:

Genetics Home Reference related topics: Alzheimer disease Cushing disease

MedlinePlus related topics: Alzheimer's Disease

Genetic and Rare Diseases Information Center resources: Alzheimer Disease Familial Hyperadrenalism

U.S. FDA Resources

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:	October 2012
Estimated Study Completion Date:	October 2013
Estimated Primary Completion Date:	April 2013 (Final data collection date for primary outcome measure)

Groups/Cohorts
Alzheimer's disease
Non demented subjects

Eligibility


Ages Eligible for Study:	50 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
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

Locations


Italy
Policlinico Universitario Campus Bio-Medico	Not yet 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 f.serino@unicampus.it

Sponsors and Collaborators

Raffaele Antonelli Incalzi

Investigators


Principal Investigator:	Francesco Maria Serino, M.D.	University Campus Bio-Medico
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

More Information

Publications:

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. Review.

Markesbery WR. Oxidative stress hypothesis in Alzheimer's disease. Free Radic Biol Med. 1997;23(1):134-47. Review.

Perry G, Nunomura A, Hirai K, Zhu X, Pérez 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. Review.

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

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.

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.

Casado A, Encarnación López-Fernández M, Concepción 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. Epub 2007 Aug 25.

Serra JA, Domínguez RO, de Lustig ES, Guareschi EM, Famulari AL, Bartolomé 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. 2001;108(10):1135-48.

Kawamoto EM, Munhoz CD, Glezer I, Bahia VS, Caramelli P, Nitrini R, Gorjão 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.

Bermejo P, Gómez-Serranillos P, Santos J, Pastor E, Gil P, Martín-Aragón 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.

Baldeiras I, Santana I, Proença 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.

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.

Onaran I, Yalçin 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.

García-Arumí E, Andreu AL, López-Hellín J, Schwartz S. Effect of oxidative stress on lymphocytes from elderly subjects. Clin Sci (Lond). 1998 Apr;94(4):447-52.

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

Costantini D, Marasco V, Møller 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. Review.

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.


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:	October 15, 2012
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:


Adrenal Gland Diseases Adrenocortical Hyperfunction Alzheimer Disease Brain Diseases Central Nervous System Diseases Delirium, Dementia, Amnestic, Cognitive Disorders	Dementia Endocrine System Diseases Mental Disorders Nervous System Diseases Neurodegenerative Diseases Tauopathies

ClinicalTrials.gov processed this record on February 27, 2015