Parkinson DiseaseLiMBaLiPNCT03937284
Lipoprotein Metabolism and Bacterial Lipopolysaccharide in Parkinson's Disease
An observational study of Parkinson Disease, run by University of Milan at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- Patients not treated
- How many people
- 45 participants
- Where
- 1 siteItaly
- Study dates
- 3 May 2016to 20 Oct 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Parkinson affected patients and healthy controls matched for sex, age and BMI in agreement with inclusion criteria.
Who may be able to join
- 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
Who cannot join
- 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
Show all 23Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Italy1 site
ASST Centro Specialistico Ortopedico Traumatologico Gaetano Pini-CTO
Milan, 20136
About this study
Official title: Lipoprotein Lipidic Composition, Lipopolysaccharide Binding Protein, and Bacterial Endotoxin Exposure in Parkinson's Disease: A Pilot Study
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.
Read the 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.
- Conditions
- Parkinson Disease
- Being tested
- Patients not treated
- Keywords
- Lipoproteins, Lipopolysaccharide, Lipopolysaccharide binding protein, Inflammation
- Medical subject headings
- Parkinson Disease, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Patients not treatedOther
| Study group | Role | What they receive |
|---|---|---|
| Parkinson's patients | Patients with Parkinson disease evaluated in agreement with UK Brain Bank criteria Receives: Other: Patients not treated | |
| Control group | Subject matched for sex, age and BMI Receives: Other: Patients not treated |
What is being measured
The primary outcome is the main question the study is designed to answer.
LPS
LPS plasma levels (EU/L)
Measured: through study completion an average of 1 year
Lipoprotein chemical composition
Cholesterol (mg/dL); HDL-cholesterol (mg/dL); triglycerides (mg/dL); phospholipids (mg/dL), apoproteins (mg/dL) of VLDL, LDL and HDL
Measured: through study completion an average of 1 year
Secondary outcomes (1)
Plasma lipid transfer proteins
Lipopolysaccharide binding protein (ng/mL), cholesterol ester transfer protein (ng/mL), phospholipid transfer protein (ng/mL)
Measured: through study completion an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2019
- Study start3 May 2016
- Primary completion20 Oct 2017
- Study completion20 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Milan
- Sponsor type
- University, hospital or other
- Collaborators
- Istituti Clinici di Perfezionamento di Milano
- Responsible party
- Principal investigator, roberta cazzola, University of Milan
- Investigators
- Roberta Cazzola, PhD, Principal investigator, University of Milan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03937284
- Sponsor's protocol ID
- Unimi
- Acronym
- LiMBaLiP
- Status last verified
- May 2019
- First submitted
- 16 Apr 2019
- Last updated
- 3 May 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
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.
PubMed 22145021Lebouvier 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.
PubMed 19712093Han 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.
PubMed 20377753Levels 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.
PubMed 15784577Hughes 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.
PubMed 11775598
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lipoprotein Lipidic Composition, Lipopolysaccharide Binding Protein, and Bacterial Endotoxin Exposure in Parkinson's Disease: A Pilot Study
- ClinicalTrials.gov ID
- NCT03937284
- Acronym / sponsor ID
- LiMBaLiP / Unimi
- Conditions
- Parkinson Disease
- Keywords
- Lipoproteins, Lipopolysaccharide, Lipopolysaccharide binding protein, Inflammation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- University of MilanUniversity, hospital or other
- Collaborators
- Istituti Clinici di Perfezionamento di Milano
- Study start
- 3 May 2016 (actual)
- Primary completion
- 20 Oct 2017 (actual)
- Study completion
- 20 Oct 2017 (actual)
- First posted
- 3 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Parkinson's patients | – | Other: Patients not treatedPatients with Parkinson disease evaluated in agreement with UK Brain Bank criteria |
| Control group | – | Other: Patients not treatedSubject matched for sex, age and BMI |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Parkinson affected patients and healthy controls matched for sex, age and BMI in agreement with inclusion criteria.
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (23 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Patients not treated | Other | Control group, Parkinson's patients |
Primary outcome
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
1 secondary outcome
Plasma lipid transfer proteins
Time frame: through study completion an average of 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2019.
- Background: PubMed 22145021Forsyth 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.
- Background: PubMed 19712093Lebouvier 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.
- Background: PubMed 20377753Han 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.
- Background: PubMed 15784577Levels 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.
- Background: PubMed 11775598Hughes 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roberta Cazzola, PhD principal investigator
University of Milan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Parkinson Disease, run by University of Milan at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
LPS (time frame: through study completion an average of 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03937284, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2019.