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Parkinson's DiseaseEarly Phase 1NCT02243982

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

A Early Phase 1 study testing [F18]-FDDNP in people with Parkinson's Disease and Parkinson-Dementia Syndrome, run by Fundacion Clinic per a la Recerca Biomédica at 1 site in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 60 years and olderHealthy volunteers can take part
What is being tested?
[F18]-FDDNP
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
1 siteSpain
Study dates
Mar 2010to Dec 2012
Phase
Early Phase 1
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 60 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • 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.

Who cannot join

  • 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);
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  • 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

Trial locations and contacts

1 site in 1 country.

Spain1 site

  • Hospital Clinic

    Barcelona, Barcelona, 08036

Other trials in Spain

About this study

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

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.
Read more

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.
Being tested
[F18]-FDDNP
Keywords
Parkinson, dementia, FDDNP, tau, beta-amyloid
Medical subject headings
Parkinson Disease, Progressive supranuclear palsy atypical, Dementia, Pick Disease of the Brain, Plaque, Amyloid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • [F18]-FDDNPOther

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

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

Study groups in NCT02243982
Study groupRoleWhat they receive
[F18]-FDDNPExperimental2-(1-{6-[(2-[fluorine-18]fluoroethyl)(methyl)amino]-2-naphthyl}-ethylidene)malononitrile. Radiopharmaceutical tracer
Receives: Other: [F18]-FDDNP

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline assessment

Secondary outcomes (2)

  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.

    Measured: 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.

    Measured: 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Sep 2014 (estimated)
  2. Study startMar 2010
  3. Primary completionJun 2011
  4. Study completionDec 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Diagnosis
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02243982
Sponsor's protocol ID
PI1080236
Status last verified
Dec 2009
First submitted
13 Aug 2014
Last updated
18 Sep 2014
Results posted
No
Data monitoring committee
No

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

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing [F18]-FDDNP in people with Parkinson's Disease and Parkinson-Dementia Syndrome, run by Fundacion Clinic per a la Recerca Biomédica at 1 site in Spain.

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 15 inclusion and 15 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 18 Sep 2014. 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 Spain. 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.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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?

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). 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 NCT02243982, which also lists 16 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 18 Sep 2014.

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