CClinicalTrials.gg
Sign In
CompletedNCT02243982Updated Sep 18, 2014

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

An Early Phase 1 interventional study of [F18]-FDDNP in Parkinson's Disease and Parkinson-Dementia Syndrome, sponsored by Fundacion Clinic per a la Recerca Biomédica. Completed at 1 site in Spain. Open to participants aged 60 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2014-09-18.

Sponsored by Fundacion Clinic per a la Recerca Biomédica · Early Phase 1, Interventional, and Diagnostic

Phase
Early Phase 1
Study type
Interventional
Enrollment
28
Allocation
Not applicable
Ages
60 Years and older
Sex
All
01

Study 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:

    • 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
    • The predictive value for the development of dementia in PD of specific patterns of PET uptake and CSF proteins profile will be established.
02

Conditions studied

  • Parkinson's Disease
  • Parkinson-Dementia Syndrome

Keywords

  • Parkinson, dementia, FDDNP, tau, beta-amyloid
03

In context

Parkinson Disease

4,487 studies on the registry are indexed under Parkinson Disease; 1,082 are open to participants now.

This study's enrollment of 28 is below the median of 40 across 3,294 interventional studies indexed under Parkinson Disease.

Browse Parkinson Disease studies →

Lead sponsor

Fundacion Clinic per a la Recerca Biomédica is the lead sponsor of 63 studies on the registry; 26 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
60 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes

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
05

Study design

Phase
Early Phase 1
Primary purpose
Diagnostic
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
28 participants (actual)

Study arms

  • Experimental
    [F18]-FDDNP

    2-(1-{6-\[(2-\[fluorine-18\]fluoroethyl)(methyl)amino\]-2-naphthyl}-ethylidene)malononitrile. Radiopharmaceutical tracer

    Other: [F18]-FDDNP

Interventions

  • Other[F18]-FDDNP

    radiopharmaceutical tracer, intravenous, single dose, of 360+/- 20 megabecquerel

    Also known as: 2-(1-{6-[(2-[fluorine-18]fluoroethyl)(methyl)amino]-2-naphthyl}-ethylidene)malononitrile

06

What researchers measure

Primary outcomes

  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.

    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.

    Time frame: Baseline assessment

Secondary outcomes

  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.

    Enzyme linked immunosorbent assay (ELISA) method will be used to assess the concentration of the biomarkers in the CSF.

    Time frame: Baseline assessment

  2. Number of patients without dementia at baseline that switch to dementia at 18 months follow-up

    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.

    Time frame: 18 months

07

Study locations

1 site
  • Hospital Clinic
    Barcelona, 08036, Spain
08

References and documents

Publications

  • Caballol N, Marti MJ, Tolosa E. Cognitive dysfunction and dementia in Parkinson disease. Mov Disord. 2007 Sep;22 Suppl 17:S358-66. doi: 10.1002/mds.21677. PubMed 18175397 ↗
  • Aarsland D, Perry R, Brown A, Larsen JP, Ballard C. Neuropathology of dementia in Parkinson's disease: a prospective, community-based study. Ann Neurol. 2005 Nov;58(5):773-6. doi: 10.1002/ana.20635. PubMed 16240351 ↗
  • Lashley T, Holton JL, Gray E, Kirkham K, O'Sullivan SS, Hilbig A, Wood NW, Lees AJ, Revesz T. Cortical alpha-synuclein load is associated with amyloid-beta plaque burden in a subset of Parkinson's disease patients. Acta Neuropathol. 2008 Apr;115(4):417-25. doi: 10.1007/s00401-007-0336-0. Epub 2008 Jan 8. PubMed 18185940 ↗
  • Jellinger KA, Wenning GK, Seppi K. Predictors of survival in dementia with lewy bodies and Parkinson dementia. Neurodegener Dis. 2007;4(6):428-30. doi: 10.1159/000107703. Epub 2007 Oct 9. PubMed 17934326 ↗
  • Blennow K, Hampel H. CSF markers for incipient Alzheimer's disease. Lancet Neurol. 2003 Oct;2(10):605-13. doi: 10.1016/s1474-4422(03)00530-1. PubMed 14505582 ↗
  • Jansen Steur E, Vermes I, de Vos RA. Cerebrospinal-fluid tau protein and aspartate aminotransferase in Parkinson's disease. Lancet. 1998 Apr 11;351(9109):1105-6. doi: 10.1016/s0140-6736(05)79387-9. No abstract available. PubMed 9660591 ↗
  • Mollenhauer B, Trenkwalder C, von Ahsen N, Bibl M, Steinacker P, Brechlin P, Schindehuette J, Poser S, Wiltfang J, Otto M. Beta-amlyoid 1-42 and tau-protein in cerebrospinal fluid of patients with Parkinson's disease dementia. Dement Geriatr Cogn Disord. 2006;22(3):200-8. doi: 10.1159/000094871. Epub 2006 Aug 7. PubMed 16899997 ↗
  • Fagan AM, Mintun MA, Mach RH, Lee SY, Dence CS, Shah AR, LaRossa GN, Spinner ML, Klunk WE, Mathis CA, DeKosky ST, Morris JC, Holtzman DM. Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans. Ann Neurol. 2006 Mar;59(3):512-9. doi: 10.1002/ana.20730. PubMed 16372280 ↗
  • Maetzler W, Reimold M, Liepelt I, Solbach C, Leyhe T, Schweitzer K, Eschweiler GW, Mittelbronn M, Gaenslen A, Uebele M, Reischl G, Gasser T, Machulla HJ, Bares R, Berg D. [11C]PIB binding in Parkinson's disease dementia. Neuroimage. 2008 Feb 1;39(3):1027-33. doi: 10.1016/j.neuroimage.2007.09.072. Epub 2007 Oct 22. PubMed 18035558 ↗
  • Agdeppa ED, Kepe V, Liu J, Flores-Torres S, Satyamurthy N, Petric A, Cole GM, Small GW, Huang SC, Barrio JR. Binding characteristics of radiofluorinated 6-dialkylamino-2-naphthylethylidene derivatives as positron emission tomography imaging probes for beta-amyloid plaques in Alzheimer's disease. J Neurosci. 2001 Dec 15;21(24):RC189. doi: 10.1523/JNEUROSCI.21-24-j0004.2001. PubMed 11734604 ↗
  • Shoghi-Jadid K, Small GW, Agdeppa ED, Kepe V, Ercoli LM, Siddarth P, Read S, Satyamurthy N, Petric A, Huang SC, Barrio JR. Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriatr Psychiatry. 2002 Jan-Feb;10(1):24-35. PubMed 11790632 ↗
  • Smid LM, Vovko TD, Popovic M, Petric A, Kepe V, Barrio JR, Vidmar G, Bresjanac M. The 2,6-disubstituted naphthalene derivative FDDNP labeling reliably predicts Congo red birefringence of protein deposits in brain sections of selected human neurodegenerative diseases. Brain Pathol. 2006 Apr;16(2):124-30. doi: 10.1111/j.1750-3639.2006.00006.x. PubMed 16768752 ↗
  • Small GW, Kepe V, Ercoli LM, Siddarth P, Bookheimer SY, Miller KJ, Lavretsky H, Burggren AC, Cole GM, Vinters HV, Thompson PM, Huang SC, Satyamurthy N, Phelps ME, Barrio JR. PET of brain amyloid and tau in mild cognitive impairment. N Engl J Med. 2006 Dec 21;355(25):2652-63. doi: 10.1056/NEJMoa054625. PubMed 17182990 ↗
  • Kepe V, Huang SC, Small GW, Satyamurthy N, Barrio JR. Visualizing pathology deposits in the living brain of patients with Alzheimer's disease. Methods Enzymol. 2006;412:144-60. doi: 10.1016/S0076-6879(06)12010-8. PubMed 17046657 ↗
  • Logan J, Fowler JS, Volkow ND, Wang GJ, Ding YS, Alexoff DL. Distribution volume ratios without blood sampling from graphical analysis of PET data. J Cereb Blood Flow Metab. 1996 Sep;16(5):834-40. doi: 10.1097/00004647-199609000-00008. PubMed 8784228 ↗
  • Buongiorno M, Antonelli F, Compta Y, Fernandez Y, Pavia J, Lomena F, Rios J, Ramirez I, Garcia JR, Soler M, Camara A, Fernandez M, Basora M, Salazar F, Sanchez-Etayo G, Valldeoriola F, Barrio JR, Marti MJ. Cross-Sectional and Longitudinal Cognitive Correlates of FDDNP PET and CSF Amyloid-beta and Tau in Parkinson's Disease1. J Alzheimers Dis. 2017;55(3):1261-1272. doi: 10.3233/JAD-160698. PubMed 27814297 ↗
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 18, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02243982
Lead sponsor
Fundacion Clinic per a la Recerca Biomédica
Responsible party
Maria Jose Martí (MD, PhD, Fundacion Clinic per a la Recerca Biomédica) — Principal investigator
First posted
Sep 18, 2014
Start date
Mar 2010
Primary completion
Jun 2011
Completion
Dec 2012
Last update
Sep 18, 2014

Study contacts

Maria Jose Martí, Md, PhD
principal investigator · Fundació per a la Recerca Biomedica

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Dec 2009. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Parkinson Disease→

Other studies from this sponsor

Fundacion Clinic per a la Recerca Biomédica

Start the discussion