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Predictive and Diagnostic Value of Tau and Beta-amyloid Markers in the Dementia of Parkinson's Disease

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ClinicalTrials.gov Identifier: NCT02243982
Recruitment Status : Completed
First Posted : September 18, 2014
Last Update Posted : September 18, 2014
Sponsor:
Information provided by (Responsible Party):
Maria Jose Martí, Fundacion Clinic per a la Recerca Biomédica

Study Description
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Brief Summary:

The PET tracer Fluoro-ethyl-methyl-amino-naphthyl-ethylidene-malononitrile ([F18]-FDDNP) has a specific affinity for lesions containing tau protein and beta-amyloid The study consists of two phases

  • In a first transversal phase, 8 neurologically unimpaired controls, 15 patients with PD and no dementia (PDND) and 8 with PD and dementia (PDD) will undergo lumbar puncture for study of tau, phospho-tau and beta-amyloid levels in cerebrospinal fluid (CSF), as well as positron emission tomography (PET) with ([F18]-FDDNP. Concentration of CSF markers and both the degree and topography of FDDNP-PET uptake will be compared among groups, along with correlation analysis between CSF and PET findings.
  • During the second phase (18 months follow-up), the PDND patients will undergo the same procedures, and cognitive changes including incident dementia will be assessed. The correlation between cognitive impairment and neurochemical and neuroimaging changes will be established to determine the predictive value of these markers.

Since the pathological lesions observed in Alzheimer disease (AD) are common in the PD and the concentrations of tau and beta-amyloid are altered in AD and PET with [F18]-FDDNP is able to separate patients with AD and cognitive impairment from controls, we hypothesized that:

  1. - Patients with PD will show a biomarkers profile similar to the AD (decreased levels of beta-amyloid and increased phospho-tau and tau) in CSF, and an abnormal uptake of [F18]-FDDNP PET compared to PDND patients and controls.
  2. -The distribution of cortical [F18]-FDDNP in the PD will be different from the AD and similar to dementia with Lewy bodies, predominantly in posterior cortical areas.
  3. PDND patients will show a [F18]-FDDNP PET uptake and levels of protein markers in CSF intermediate between controls and patients with PD.
  4. -In the subsequent follow-up, PDND patients will show cognitive impairment correlate to changes in the levels of protein markers in CSF and uptake of PET with [F18]-FDDNP
  5. - The predictive value for the development of dementia in PD of specific patterns of PET uptake and CSF proteins profile will be established.

Condition or disease Intervention/treatment Phase
Parkinson's Disease Parkinson-Dementia Syndrome Other: [F18]-FDDNP Early Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Predictive and Diagnostic Value of Tau and Beta-amyloid Markers in Cerebrospinal Fluid and Positron Emission Tomography in the Dementia of Parkinson's Disease
Study Start Date : March 2010
Actual Primary Completion Date : June 2011
Actual Study Completion Date : December 2012

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Arms and Interventions
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Arm Intervention/treatment
Experimental: [F18]-FDDNP
2-(1-{6-[(2-[fluorine-18]fluoroethyl)(methyl)amino]-2-naphthyl}-ethylidene)malononitrile. Radiopharmaceutical tracer
 Other: [F18]-FDDNP
radiopharmaceutical tracer, intravenous, single dose, of 360+/- 20 megabecquerel
Other Name: 2-(1-{6-[(2-[fluorine-18]fluoroethyl)(methyl)amino]-2-naphthyl}-ethylidene)malononitrile


Outcome Measures
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Primary Outcome Measures :
  1. Relative Volume of Distribution of [F18]-FDDNP in non-demented patients with Parkinson's disease (PDND), demented patients with Parkinson's disease (PDD) and controls. [ Time Frame: Baseline assessment ]
    To asses the [F18]-FDDNP PET uptake in non-demented patients with Parkinson's disease (PDND), demented patients with Parkinson's disease (PDD) and controls.


Secondary Outcome Measures :
  1. Concentration ( pg/mL) of beta-amyloid, tau and phospho-tau in cerebrospinal fluid (CSF) of non-demented patients with Parkinson's disease (PDND), demented patients with Parkinson's disease (PDD) and controls. [ Time Frame: Baseline assessment ]
    Enzyme linked immunosorbent assay (ELISA) method will be used to assess the concentration of the biomarkers in the CSF.

  2. Number of patients without dementia at baseline that switch to dementia at 18 months follow-up [ Time Frame: 18 months ]
    PDND group will be followed-up at 18 months to assess the number of patient that develops dementia, using the criteria of Diagnostic and Statistical Manual of Mental Disorders version IV.


Eligibility Criteria
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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Inclusion Criteria PDD

  • Male or female ≥ 60 years old;
  • Diagnose of PD probable or definite according to criteria of the United Kingdom Parkinson's Disease Society Brain Bank;
  • The Hoehn & Yahr stage of the disease between 3 and 5 in off state;
  • Diagnose of dementia established according to the fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the diagnostic guidelines for dementia of the Movement Disorders Society (MDS);
  • The score of the Mini-Mental State Examination of Folstein (MMSE) <24;
  • The score on the Mattis Dementia Rating Scale (MDRS) <136.

Inclusion criteria PDND:

  • Male or female ≥ 60 years old;
  • Diagnose of PD probable or definite according to criteria of the United Kingdom Parkinson's Disease Society Brain Bank;
  • The Hoehn & Yahr stage of the disease between 3 and 5 in OFF state;
  • The score of the Mini-Mental State Examination of Folstein (MMSE) ≥24;
  • The score on the Mattis Dementia Rating Scale (MDRS) ≥136.

Inclusion criteria Controls:

  • Male or female ≥ 60 years old;
  • No known diagnosis of neuropsychiatric diseases
  • The score of the Mini-Mental State Examination of Folstein (MMSE) ≥24;
  • The score on the Mattis Dementia Rating Scale (MDRS) ≥136.

Exclusion Criteria:

  • The subject is pregnant or breastfeeding;
  • The subject has a history of drug abuse or alcohol;
  • The subject has developed dementia in the first year of parkinsonism or before than parkinsonism;
  • The subject meets criteria for vascular dementia;
  • The subject has symptoms suggestive of other types of parkinsonism (multi-system atrophy cortico-basal, supra-nuclear palsy progressive degeneration) or degenerative dementia (fronto-temporal dementia);
  • The subject has a moderate or severe renal functional impairment (serum creatinine> 1.5 mg / dL);
  • The subject has a moderate or severe hepatic impairment (bilirubin> 2 times the upper limit of normal, transaminases> 3 times the upper limit of normal);
  • The subject presents structural abnormalities in basal ganglia or cortical level on magnetic resonance imaging or computerized tomography;
  • The subject has participated in a clinical study with an investigational drug product within 30 days prior to screening and / or radiopharmaceutical in a minimum period of 5 radioactive half-lives prior to screening;
  • Occupational exposure to radiation> 15 milliSievert (mSv) / year
  • The subject has received treatment with non-steroidal anti-inflammatory drugs during the 30-day period before the PET scan
  • The subject has allergy to the investigational product or any of its components;
  • The subject has a clinically active, serious disease with a reduced life expectancy;
  • The subject is claustrophobic / a.
  • The subject has received in the last 364 days a dose of ionizing radiation that coupled with the study dose exceeds 10 mSv
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02243982


Locations
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Spain
Hospital Clinic
Barcelona, Spain, 08036
Sponsors and Collaborators
Fundacion Clinic per a la Recerca Biomédica
Investigators
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Principal Investigator: Maria Jose Martí, Md, PhD Fundació per a la Recerca Biomedica
More Information
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Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Maria Jose Martí, MD, PhD, Fundacion Clinic per a la Recerca Biomédica
ClinicalTrials.gov Identifier: NCT02243982    
Other Study ID Numbers: PI1080236
First Posted: September 18, 2014    Key Record Dates
Last Update Posted: September 18, 2014
Last Verified: December 2009
Keywords provided by Maria Jose Martí, Fundacion Clinic per a la Recerca Biomédica:
Parkinson, dementia, FDDNP, tau, beta-amyloid
Additional relevant MeSH terms:
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Parkinson Disease
Dementia
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
 Nervous System Diseases
Movement Disorders
Synucleinopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders