Clinical trial NCT02243982: Predictive and Diagnostic Value of Tau and Beta-amyloid Markers in the Dementia of Parkinson's Disease
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Parkinson's Disease
Parkinson-Dementia Syndrome
Keywords: Parkinson, dementia, FDDNP, tau, beta-amyloid
Lead sponsor: Fundacion Clinic per a la Recerca Biomédica
Sponsor class: OTHER
First posted: 2014-09-18
Enrollment: 28
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.


Eligibility 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

Primary outcomes:
measure: 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.
timeFrame: Baseline assessment
Secondary outcomes:
measure: 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.
timeFrame: Baseline assessment
measure: Number of patients without dementia at baseline that switch to dementia at 18 months follow-up
timeFrame: 18 months
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Clinic
Study officials:
affiliation: Fundació per a la Recerca Biomedica
name: Maria Jose Martí, Md, PhD
role: PRINCIPAL_INVESTIGATOR
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