<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02214862</url>
  </required_header>
  <id_info>
    <org_study_id>PI11/02031</org_study_id>
    <nct_id>NCT02214862</nct_id>
  </id_info>
  <brief_title>2-(1-{6-[(2-[F-18]Fluoroethyl) (Methyl)Amino]-2-naphthyl} Ethylidene) Malononitrile-PET for in Vivo Diagnose of Tauopathy in Unclassified Parkinsonism</brief_title>
  <acronym>[F18]-FDDNP</acronym>
  <official_title>Pilot, Exploratory Study With [F18]-FDDNP-PET for in Vivo Diagnose of Tauopathy in Unclassified Parkinsonism</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundacion Clinic per a la Recerca Biomédica</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fundacion Clinic per a la Recerca Biomédica</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The PET tracer [F18]-FDDNP has a specific affinity for lesions containing tau protein.&#xD;
&#xD;
      The study consists of two phases:&#xD;
&#xD;
        -  In the first (cross-sectional) phase it will be assessed the uptake of [18F]-FDDNP in 10&#xD;
           cases with progressive supranuclear palsy (PSP, a tauopathy) en 10 with multi-system&#xD;
           atrophy (MSA, a non-tauopathy), along with 20 individuals with Unclassifiable&#xD;
           Parkinsonism, as previously defined in a European cohort study.&#xD;
&#xD;
        -  In the second (longitudinal) phase it will be prospectively followed the 20&#xD;
           unclassifiable patients (at 6, 12 and 18 months) by means of validated scales and&#xD;
           accepted diagnostic criteria in order to try to correlate their eventual clinical&#xD;
           diagnosis with baseline PET findings. On this basis, we endeavour to estimate the&#xD;
           ability of this technique to detect in vivo underlying tau pathology in subjects&#xD;
           initially unclassifiable on clinical grounds.&#xD;
&#xD;
      We hypothesized that:&#xD;
&#xD;
        1. Patients with clinically definite PSP will present an increased uptake in basal ganglia,&#xD;
           brainstem and cerebellum.&#xD;
&#xD;
        2. Patients with clinically defined MSA will not present specific uptake.&#xD;
&#xD;
        3. Part of unclassifiable patients with parkinsonism will present a pattern of uptake&#xD;
           similar to patients with clinically defined PSP and this part along the clinical&#xD;
           follow-up will be meet clinical criteria for diagnose of PSP&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 2013</start_date>
  <completion_date type="Actual">February 2016</completion_date>
  <primary_completion_date type="Actual">December 2015</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>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.</measure>
    <time_frame>18 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>to assess the uptake of [18F]-FDDNP in cases clinically defined of progressive supranuclear palsy and multi-system atrophy</measure>
    <time_frame>Baseline assessment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess the ability to detect in vivo underlying tau pathology in unclassifiable parkinsonism by means of PET -[18F]-FDDNP.</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Progressive Supranuclear Palsy</condition>
  <condition>Multi-System Atrophy</condition>
  <condition>Parkinsonism</condition>
  <arm_group>
    <arm_group_label>[F18]-FDDNP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2-(1-{6-[(2-[F-18]fluoroethyl) (methyl)amino]-2-naphthyl} ethylidene) malononitrile Radiopharmaceutical tracer, intravenous, single dose of 360+/-20 megabecquerel</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[F18]-FDDNP</intervention_name>
    <description>radiopharmaceutical tracer</description>
    <arm_group_label>[F18]-FDDNP</arm_group_label>
    <other_name>22-(1-{6-[(2-[F-18]fluoroethyl) (methyl)amino]-2-naphthyl} ethylidene) malononitrile</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The subject is male or female ≥ 40 years old;&#xD;
&#xD;
          -  The individual has one of these three conditions:&#xD;
&#xD;
          -  probable PSP according to criteria of the National Institute of Neurological Disorders&#xD;
             and Stroke (NINDS)&#xD;
&#xD;
          -  probable MSA according to criteria of the Second consensus statement on the diagnosis&#xD;
             of multiple system atrophy&#xD;
&#xD;
          -  unclassifiable parkinsonism according to criteria defined by Katzenschlager et al,&#xD;
             2003:&#xD;
&#xD;
          -  Patients with atypical parkinsonism without response to treatment with levodopa and&#xD;
             does not meet any of the diagnostic criteria for other known atypical parkinsonism&#xD;
&#xD;
          -  Patient given written consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The subject is diagnosed with Parkinson's Disease and meets the diagnostic criteria&#xD;
             United Kingdom Parkinson's Disease Society Brain Bank -The subject is pregnant or&#xD;
             breastfeeding;&#xD;
&#xD;
          -  The subject has a history of drug abuse or alcohol;&#xD;
&#xD;
          -  The subject has a moderate or severe renal function impairment (creatinine serum&gt; 1.5&#xD;
             mg / dL);&#xD;
&#xD;
          -  The subject has a moderate or severe hepatic impairment (bilirubin&gt; 2 times the upper&#xD;
             limit of normal, transaminases&gt; 3 times the limit top of normal);&#xD;
&#xD;
          -  The subject presents structural abnormalities in the basal ganglia or cortical level&#xD;
             on MRI or CT;&#xD;
&#xD;
          -  The subject has participated in a clinical study with a pharmaceutical product&#xD;
             investigation within 30 days prior to screening and / or a radiopharmaceutical minimum&#xD;
             period of 5 radioactive half-lives prior to screening;&#xD;
&#xD;
          -  Occupational exposure to radiation&gt; 15 milliSievert (mSv) / year&#xD;
&#xD;
          -  Use of nonsteroidal antiinflammatory drug (NSAIDs), for some reason, can not be&#xD;
             replaced by any other drug 4 weeks before the PET scan;&#xD;
&#xD;
          -  The subject has allergy investigational product or any of its components;&#xD;
&#xD;
          -  The subject has a clinically severe active disease, with a hope reduced life;&#xD;
&#xD;
          -  The subject is claustrophobic / a.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Maria Jose Martí, Md, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fundació per a la Recerca Biomedica</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Clinic</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <reference>
    <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. doi: 10.1002/mds.10523.</citation>
    <PMID>14534915</PMID>
  </reference>
  <reference>
    <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. doi: 10.1002/mds.10459.</citation>
    <PMID>12722160</PMID>
  </reference>
  <reference>
    <citation>Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, Wood NW, Colosimo C, Durr 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.</citation>
    <PMID>18725592</PMID>
  </reference>
  <reference>
    <citation>Golbe LI, Ohman-Strickland PA. A clinical rating scale for progressive supranuclear palsy. Brain. 2007 Jun;130(Pt 6):1552-65. doi: 10.1093/brain/awm032. Epub 2007 Apr 2.</citation>
    <PMID>17405767</PMID>
  </reference>
  <reference>
    <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. doi: 10.1002/mds.20255.</citation>
    <PMID>15452868</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>19882153</PMID>
  </reference>
  <reference>
    <citation>Buongiorno M, Compta Y, Marti MJ. Amyloid-beta and tau 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.</citation>
    <PMID>21764078</PMID>
  </reference>
  <reference>
    <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. doi: 10.1111/j.1750-3639.2006.00006.x.</citation>
    <PMID>16768752</PMID>
  </reference>
  <verification_date>February 2016</verification_date>
  <study_first_submitted>August 11, 2014</study_first_submitted>
  <study_first_submitted_qc>August 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 12, 2014</study_first_posted>
  <last_update_submitted>February 3, 2016</last_update_submitted>
  <last_update_submitted_qc>February 3, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 4, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fundacion Clinic per a la Recerca Biomédica</investigator_affiliation>
    <investigator_full_name>Maria Jose Martí</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Unclassifiable Parkinsonism, [F18]-FDDNP-PET, Tauopathy, PSP,MSA</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinsonian Disorders</mesh_term>
    <mesh_term>Supranuclear Palsy, Progressive</mesh_term>
    <mesh_term>Tauopathies</mesh_term>
    <mesh_term>Multiple System Atrophy</mesh_term>
    <mesh_term>Shy-Drager Syndrome</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02214862
org study id: PI11/02031
nct id: NCT02214862
lead sponsor: 
has dmc: Yes
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
allocation: N/A
intervention model: Single Group Assignment
masking: None (Open Label)
measure: 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.
time frame: 18 months
measure: to assess the uptake of [18F]-FDDNP in cases clinically defined of progressive supranuclear palsy and multi-system atrophy
time frame: Baseline assessment
measure: To assess the ability to detect in vivo underlying tau pathology in unclassifiable parkinsonism by means of PET -[18F]-FDDNP.
time frame: 18 months
arm group label: [F18]-FDDNP
arm group type: Experimental
description: 2-(1-{6-[(2-[F-18]fluoroethyl) (methyl)amino]-2-naphthyl} ethylidene) malononitrile Radiopharmaceutical tracer, intravenous, single dose of 360+/-20 megabecquerel
intervention type: Drug
intervention name: [F18]-FDDNP
description: radiopharmaceutical tracer
arm group label: [F18]-FDDNP
other name: 22-(1-{6-[(2-[F-18]fluoroethyl) (methyl)amino]-2-naphthyl} ethylidene) malononitrile
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Maria Jose Martí, Md, PhD
role: Principal Investigator
affiliation: Fundació per a la Recerca Biomedica
facility: 
country: Spain
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. doi: 10.1002/mds.10523.
PMID: 14534915
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. doi: 10.1002/mds.10459.
PMID: 12722160
citation: Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, Wood NW, Colosimo C, Durr 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.
PMID: 18725592
citation: Golbe LI, Ohman-Strickland PA. A clinical rating scale for progressive supranuclear palsy. Brain. 2007 Jun;130(Pt 6):1552-65. doi: 10.1093/brain/awm032. Epub 2007 Apr 2.
PMID: 17405767
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. doi: 10.1002/mds.20255.
PMID: 15452868
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.
PMID: 19882153
citation: Buongiorno M, Compta Y, Marti MJ. Amyloid-beta and tau 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.
PMID: 21764078
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. doi: 10.1111/j.1750-3639.2006.00006.x.
PMID: 16768752
responsible party type: Principal Investigator
investigator affiliation: Fundacion Clinic per a la Recerca Biomédica
investigator full name: Maria Jose Martí
investigator title: MD, PhD
mesh term: Parkinsonian Disorders
mesh term: Supranuclear Palsy, Progressive
mesh term: Tauopathies
mesh term: Multiple System Atrophy
mesh term: Shy-Drager Syndrome