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

September 16, 2014 updated by: Maria Jose Martí, Fundacion Clinic per a la Recerca Biomédica

Predictive and Diagnostic Value of Tau and Beta-amyloid Markers in Cerebrospinal Fluid and Positron Emission Tomography in the Dementia of Parkinson's Disease

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelona, Spain, 08036
        • Hospital Clínic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

56 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 2-(1-{6-[(2-[fluorine-18]fluoroethyl)(methyl)amino]-2-naphthyl}-ethylidene)malononitrile

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline assessment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline assessment
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.
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fundacion Clinic per a la Recerca Biomédica

Investigators

  • Principal Investigator: Maria Jose Martí, Md, PhD, Fundació per a la Recerca Biomedica

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2010

Primary Completion (Actual)

June 1, 2011

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

August 13, 2014

First Submitted That Met QC Criteria

September 16, 2014

First Posted (Estimate)

September 18, 2014

Study Record Updates

Last Update Posted (Estimate)

September 18, 2014

Last Update Submitted That Met QC Criteria

September 16, 2014

Last Verified

December 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PI1080236

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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