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出境医 / 临床实验 / Lipoprotein Metabolism and Bacterial Lipopolysaccharide in Parkinson's Disease (LiMBaLiP)

Lipoprotein Metabolism and Bacterial Lipopolysaccharide in Parkinson's Disease (LiMBaLiP)

Study Description
Brief Summary:

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.


Condition or disease Intervention/treatment
Parkinson Disease Other: Patients not treated

Detailed Description:

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.

Study Design
Layout table for study information
Study Type : Observational
Actual Enrollment : 45 participants
Observational Model: Case-Only
Time Perspective: Cross-Sectional
Official Title: Lipoprotein Lipidic Composition, Lipopolysaccharide Binding Protein, and Bacterial Endotoxin Exposure in Parkinson's Disease: A Pilot Study
Actual Study Start Date : May 3, 2016
Actual Primary Completion Date : October 20, 2017
Actual Study Completion Date : October 20, 2017
Arms and Interventions
Group/Cohort Intervention/treatment
Parkinson's patients
Patients with Parkinson disease evaluated in agreement with UK Brain Bank criteria
Other: Patients not treated
Control group
Subject matched for sex, age and BMI
Other: Patients not treated
Outcome Measures
Primary Outcome Measures :
  1. LPS [ Time Frame: through study completion an average of 1 year ]
    LPS plasma levels (EU/L)

  2. Lipoprotein chemical composition [ Time Frame: through study completion an average of 1 year ]
    Cholesterol (mg/dL); HDL-cholesterol (mg/dL); triglycerides (mg/dL); phospholipids (mg/dL), apoproteins (mg/dL) of VLDL, LDL and HDL


Secondary Outcome Measures :
  1. Plasma lipid transfer proteins [ Time Frame: through study completion an average of 1 year ]
    Lipopolysaccharide binding protein (ng/mL), cholesterol ester transfer protein (ng/mL), phospholipid transfer protein (ng/mL)


Biospecimen Retention:   Samples Without DNA
Plasma and erythrocytes

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Parkinson affected patients and healthy controls matched for sex, age and BMI in agreement with inclusion criteria.
Criteria

Parkinson's patients

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

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

Inclusion criteria

  • 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.
Contacts and Locations

Locations
Layout table for location information
Italy
ASST Centro Specialistico Ortopedico Traumatologico Gaetano Pini-CTO
Milan, Italy, 20136
Sponsors and Collaborators
University of Milan
Istituti Clinici di Perfezionamento di Milano
Investigators
Layout table for investigator information
Principal Investigator: Roberta Cazzola, PhD University of Milan
Tracking Information
First Submitted Date April 16, 2019
First Posted Date May 3, 2019
Last Update Posted Date May 3, 2019
Actual Study Start Date May 3, 2016
Actual Primary Completion Date October 20, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: May 2, 2019)
  • LPS [ Time Frame: through study completion an average of 1 year ]
    LPS plasma levels (EU/L)
  • Lipoprotein chemical composition [ Time Frame: through study completion an average of 1 year ]
    Cholesterol (mg/dL); HDL-cholesterol (mg/dL); triglycerides (mg/dL); phospholipids (mg/dL), apoproteins (mg/dL) of VLDL, LDL and HDL
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: May 2, 2019)
Plasma lipid transfer proteins [ Time Frame: through study completion an average of 1 year ]
Lipopolysaccharide binding protein (ng/mL), cholesterol ester transfer protein (ng/mL), phospholipid transfer protein (ng/mL)
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Lipoprotein Metabolism and Bacterial Lipopolysaccharide in Parkinson's Disease
Official Title Lipoprotein Lipidic Composition, Lipopolysaccharide Binding Protein, and Bacterial Endotoxin Exposure in Parkinson's Disease: A Pilot Study
Brief Summary

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

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.

Study Type Observational
Study Design Observational Model: Case-Only
Time Perspective: Cross-Sectional
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
Plasma and erythrocytes
Sampling Method Non-Probability Sample
Study Population Parkinson affected patients and healthy controls matched for sex, age and BMI in agreement with inclusion criteria.
Condition Parkinson Disease
Intervention Other: Patients not treated
Study Groups/Cohorts
  • Parkinson's patients
    Patients with Parkinson disease evaluated in agreement with UK Brain Bank criteria
    Intervention: Other: Patients not treated
  • Control group
    Subject matched for sex, age and BMI
    Intervention: Other: Patients not treated
Publications *
  • 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.
  • 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. Review.
  • 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. Review.
  • 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.
  • 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: May 2, 2019)
45
Original Actual Enrollment Same as current
Actual Study Completion Date October 20, 2017
Actual Primary Completion Date October 20, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria

Parkinson's patients

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

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

Inclusion criteria

  • 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.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Italy
Removed Location Countries  
 
Administrative Information
NCT Number NCT03937284
Other Study ID Numbers Unimi
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party roberta cazzola, University of Milan
Study Sponsor University of Milan
Collaborators Istituti Clinici di Perfezionamento di Milano
Investigators
Principal Investigator: Roberta Cazzola, PhD University of Milan
PRS Account University of Milan
Verification Date May 2019