Lipoprotein Metabolism and Bacterial Lipopolysaccharide in Parkinson's Disease

NCT ID: NCT03937284

Last Updated: 2019-05-03

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

45 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-05-03

Study Completion Date

2017-10-20

Brief Summary

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Patients with Parkinson's disease (PD) present an impaired intestinal permeability with consequent lipopolysaccharide (LPS) translocation in the systemic circulation. Plasmatic lipoproteins play a key role in the detoxification of LPS.

The investigators aim to study the relationships between lipoprotein chemical composition and plasma LPS circulation in PD.

Detailed Description

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Bacterial lipopolysaccharides are able to produce neuroinflammation and dopaminergic receptors degeneration. In addition, they may produce an accumulation of α-synuclein in the area of the substantia Nigra. Recent studies have shown that α-synuclein aggregates may be present also in gastrointestinal neurons of patients with PD. This last finding led to the hypothesis that the intestine might be an early site of PD disease in response to an environmental toxin or pathogen. Forsyth et al. have discovered an impaired intestinal permeability in subjects with recently diagnosed PD, and they found positive correlations between this factor, exposure to LPS and alpha-synuclein accumulation in gastrointestinal neurons. Plasma lipoproteins play a key role in the detoxification of bacterial endotoxins. Lipoprotein chemical composition is related to their detoxing properties. To the best of investigator knowledge, the relationships between lipoprotein chemical composition and LPS in PD have not yet been investigated. Therefore, the aims of this study are: I) to evaluate the chemical composition of VLDL, LDL and HDL in subjects with PD compared to a control group; 2) to analyze the activity of plasma lipid transfer proteins and LPS plasma levels in the same groups of subjects; III) finally, to investigate the correlations between the analyzed parameters.

Subjects and method Twenty patients with PD and twenty healthy controls were recruited for the study. Fasting blood samples were taken for routine laboratory analysis and for the separation of EDTA plasma. Plasma samples stored at -80°C until were used for lipoprotein isolation and analysis and for the measurement of lipid transfer protein and LPS levels.

Conditions

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Parkinson Disease

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Parkinson's patients

Patients with Parkinson disease evaluated in agreement with UK Brain Bank criteria

Patients not treated

Intervention Type OTHER

Control group

Subject matched for sex, age and BMI

Patients not treated

Intervention Type OTHER

Interventions

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Patients not treated

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of Parkinson disease in agreement with UK Brain Bank
* Farmacological treatment with L-Dopa and/or dopaminergic agonist or diagnosis de novo
* BMI 18.5 - 29.9 kg/m\^2
* Informed consent signature


* Absence of major disease
* BMI 18.5 - 29.9 kg/m\^2
* Informed consent signature

Exclusion Criteria

* Presence of type 1 and type 2 diabetes mellitus
* Presence of major chronic diseases of the digestive tract.
* Pregnancy in progress
* Subjects subjected to antihypertensive therapies or statins or with drugs that can change metabolic status and insulin sensitivity (e.g. chronic oral steroid therapy)
* Subjects affected by endocrine pathologies (e.g. Cushing disease, uncontrolled thyroid disease)
* Presence of known renal insufficiency or creatinine levels greater than 1.8 mg/dl
* Presence of chronic liver disease or ALT and AST levels exceeding two standard deviations from normal levels
* Presence of malignant disease
* Alcohol or drug abuse
* Major psychiatric disorders
* Subjects dedicated to intense and agonistic physical activity.

Control group


* Presence of type 1 and type 2 diabetes mellitus
* Presence of major chronic diseases of the digestive tract.
* Pregnancy in progress
* Subjects subjected to antihypertensive therapies or statins or with drugs that can change metabolic status and insulin sensitivity (e.g. chronic oral steroid therapy)
* Subjects affected by endocrine pathologies (e.g. Cushing disease, uncontrolled thyroid disease)
* Presence of known renal insufficiency or creatinine levels greater than 1.8 mg/dl
* Presence of chronic liver disease or ALT and AST levels exceeding two standard deviations from normal levels
* Presence of malignant disease
* Alcohol or drug abuse
* Major psychiatric disorders
* Subjects dedicated to intense and agonistic physical activity.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Istituti Clinici di Perfezionamento di Milano

OTHER

Sponsor Role collaborator

University of Milan

OTHER

Sponsor Role lead

Responsible Party

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roberta cazzola

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Roberta Cazzola, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Milan

Locations

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ASST Centro Specialistico Ortopedico Traumatologico Gaetano Pini-CTO

Milan, , Italy

Site Status

Countries

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Italy

References

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Forsyth CB, Shannon KM, Kordower JH, Voigt RM, Shaikh M, Jaglin JA, Estes JD, Dodiya HB, Keshavarzian A. Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson's disease. PLoS One. 2011;6(12):e28032. doi: 10.1371/journal.pone.0028032. Epub 2011 Dec 1.

Reference Type BACKGROUND
PMID: 22145021 (View on PubMed)

Lebouvier T, Chaumette T, Paillusson S, Duyckaerts C, Bruley des Varannes S, Neunlist M, Derkinderen P. The second brain and Parkinson's disease. Eur J Neurosci. 2009 Sep;30(5):735-41. doi: 10.1111/j.1460-9568.2009.06873.x. Epub 2009 Aug 27.

Reference Type BACKGROUND
PMID: 19712093 (View on PubMed)

Han R. Plasma lipoproteins are important components of the immune system. Microbiol Immunol. 2010 Apr;54(4):246-53. doi: 10.1111/j.1348-0421.2010.00203.x.

Reference Type BACKGROUND
PMID: 20377753 (View on PubMed)

Levels JH, Marquart JA, Abraham PR, van den Ende AE, Molhuizen HO, van Deventer SJ, Meijers JC. Lipopolysaccharide is transferred from high-density to low-density lipoproteins by lipopolysaccharide-binding protein and phospholipid transfer protein. Infect Immun. 2005 Apr;73(4):2321-6. doi: 10.1128/IAI.73.4.2321-2326.2005.

Reference Type BACKGROUND
PMID: 15784577 (View on PubMed)

Hughes AJ, Ben-Shlomo Y, Daniel SE, Lees AJ. What features improve the accuracy of clinical diagnosis in Parkinson's disease: a clinicopathologic study. 1992. Neurology. 2001 Nov;57(10 Suppl 3):S34-8. No abstract available.

Reference Type BACKGROUND
PMID: 11775598 (View on PubMed)

Other Identifiers

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Unimi

Identifier Type: -

Identifier Source: org_study_id

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