2-(1-{6-[(2-[F-18]Fluoroethyl) (Methyl)Amino]-2-naphthyl} Ethylidene) Malononitrile-PET for in Vivo Diagnose of Tauopathy in Unclassified Parkinsonism

Progressive Supranuclear Palsy Clinical Trial

— [F18]-FDDNP  

Official title:

Pilot, Exploratory Study With [F18]-FDDNP-PET for in Vivo Diagnose of Tauopathy in Unclassified Parkinsonism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02214862
• Other study ID #: PI11/02031
• Status: Completed
• Phase: Phase 0
• First received: August 11, 2014
• Last updated: February 3, 2016
• Start date: March 2013
• Est. completion date: February 2016

Study information

• Verified date: February 2016
• Source: Fundacion Clinic per a la Recerca Biomédica
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical Trial Summary

The PET tracer [F18]-FDDNP has a specific affinity for lesions containing tau protein.

The study consists of two phases:

• In the first (cross-sectional) phase it will be assessed the uptake of [18F]-FDDNP in 10 cases with progressive supranuclear palsy (PSP, a tauopathy) en 10 with multi-system atrophy (MSA, a non-tauopathy), along with 20 individuals with Unclassifiable Parkinsonism, as previously defined in a European cohort study.

• In the second (longitudinal) phase it will be prospectively followed the 20 unclassifiable patients (at 6, 12 and 18 months) by means of validated scales and accepted diagnostic criteria in order to try to correlate their eventual clinical diagnosis with baseline PET findings. On this basis, we endeavour to estimate the ability of this technique to detect in vivo underlying tau pathology in subjects initially unclassifiable on clinical grounds.

We hypothesized that:

1. Patients with clinically definite PSP will present an increased uptake in basal ganglia, brainstem and cerebellum.

2. Patients with clinically defined MSA will not present specific uptake.

3. Part of unclassifiable patients with parkinsonism will present a pattern of uptake similar to patients with clinically defined PSP and this part along the clinical follow-up will be meet clinical criteria for diagnose of PSP

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: February 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• The subject is male or female = 40 years old;

• The individual has one of these three conditions:

• probable PSP according to criteria of the National Institute of Neurological Disorders and Stroke (NINDS)

• probable MSA according to criteria of the Second consensus statement on the diagnosis of multiple system atrophy

• unclassifiable parkinsonism according to criteria defined by Katzenschlager et al, 2003:

• Patients with atypical parkinsonism without response to treatment with levodopa and does not meet any of the diagnostic criteria for other known atypical parkinsonism

• Patient given written consent

Exclusion Criteria:

• The subject is diagnosed with Parkinson's Disease and meets the diagnostic criteria United Kingdom Parkinson's Disease Society Brain Bank -The subject is pregnant or breastfeeding;

• The subject has a history of drug abuse or alcohol;

• The subject has a moderate or severe renal function impairment (creatinine serum> 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 limit top of normal);

• The subject presents structural abnormalities in the basal ganglia or cortical level on MRI or CT;

• The subject has participated in a clinical study with a pharmaceutical product investigation within 30 days prior to screening and / or a radiopharmaceutical minimum period of 5 radioactive half-lives prior to screening;

• Occupational exposure to radiation> 15 milliSievert (mSv) / year

• Use of nonsteroidal antiinflammatory drug (NSAIDs), for some reason, can not be replaced by any other drug 4 weeks before the PET scan;

• The subject has allergy investigational product or any of its components;

• The subject has a clinically severe active disease, with a hope reduced life;

• The subject is claustrophobic / a.

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Multi-System Atrophy
• Multiple System Atrophy
• Parkinsonian Disorders
• Parkinsonism
• Progressive Supranuclear Palsy
• Supranuclear Palsy, Progressive
• Tauopathies

Intervention

Drug:
• [F18]-FDDNP
radiopharmaceutical tracer

Locations

Country	Name	City	State
Spain	Hospital Clinic	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Fundacion Clinic per a la Recerca Biomédica

Country where clinical trial is conducted

Spain, 

References & Publications (8)

Buongiorno M, Compta Y, Martí MJ. Amyloid-ß and t biomarkers in Parkinson's disease-dementia. J Neurol Sci. 2011 Nov 15;310(1-2):25-30. doi: 10.1016/j.jns.2011.06.046. Epub 2011 Jul 20. Review. — View Citation

Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, Wood NW, Colosimo C, Dürr A, Fowler CJ, Kaufmann H, Klockgether T, Lees A, Poewe W, Quinn N, Revesz T, Robertson D, Sandroni P, Seppi K, Vidailhet M. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008 Aug 26;71(9):670-6. doi: 10.1212/01.wnl.0000324625.00404.15. — View Citation

Golbe LI, Ohman-Strickland PA. A clinical rating scale for progressive supranuclear palsy. Brain. 2007 Jun;130(Pt 6):1552-65. Epub 2007 Apr 2. — View Citation

Katzenschlager R, Cardozo A, Avila Cobo MR, Tolosa E, Lees AJ. Unclassifiable parkinsonism in two European tertiary referral centres for movement disorders. Mov Disord. 2003 Oct;18(10):1123-31. — View Citation

Litvan I, Bhatia KP, Burn DJ, Goetz CG, Lang AE, McKeith I, Quinn N, Sethi KD, Shults C, Wenning GK; Movement Disorders Society Scientific Issues Committee. Movement Disorders Society Scientific Issues Committee report: SIC Task Force appraisal of clinical diagnostic criteria for Parkinsonian disorders. Mov Disord. 2003 May;18(5):467-86. — View Citation

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. — View Citation

Wenning GK, Tison F, Seppi K, Sampaio C, Diem A, Yekhlef F, Ghorayeb I, Ory F, Galitzky M, Scaravilli T, Bozi M, Colosimo C, Gilman S, Shults CW, Quinn NP, Rascol O, Poewe W; Multiple System Atrophy Study Group. Development and validation of the Unified Multiple System Atrophy Rating Scale (UMSARS). Mov Disord. 2004 Dec;19(12):1391-402. — View Citation

Wong KP, Wardak M, Shao W, Dahlbom M, Kepe V, Liu J, Satyamurthy N, Small GW, Barrio JR, Huang SC. Quantitative analysis of [18F]FDDNP PET using subcortical white matter as reference region. Eur J Nucl Med Mol Imaging. 2010 Mar;37(3):575-88. doi: 10.1007/s00259-009-1293-8. Epub 2009 Oct 31. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the Relative Volume of Distribution of [18F]-FDDNP in individuals with unclassifiable parkinsonism, and to try to correlate their eventual clinical diagnosis with baseline PET findings.		18 months	No
Secondary	to assess the uptake of [18F]-FDDNP in cases clinically defined of progressive supranuclear palsy and multi-system atrophy		Baseline assessment	No
Secondary	To assess the ability to detect in vivo underlying tau pathology in unclassifiable parkinsonism by means of PET -[18F]-FDDNP.		18 months	No