Trial document




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  DRKS00000472

Trial Description

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Title

Clinical evaluation of the new nicotinic receptor marker (-)- [18F]NCFHEB with Positron Emission Tomography in Alzheimer’s disease patients, and healthy volunteers

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

In the course of the trial it will be determined, whether a new radioactively labelled tracer molecule (NCFHEB) in combination with positro emission spectroscopy (PET) can be used for the early diagnosis of Alzheimer's disease.

Therefore it will be analyzed, whether the PET measuring-data will differ between healthy volunteers and Alzheimer patient's, potentially allowing a specific diagnosis.

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Brief Summary in Scientific Language

For an early and effective treatment of Alzheimer’s disease (AD) early diagnostic markers are urgently needed. First positron emission tomography (PET) studies using radioligands for nicotinic receptors suggest that the quantification of nicotinic receptors is a promising approach to detect AD in a very early clinical stage. The aim of the clinical trial is the preclinical testing (i.e. radiotracer metabolism, dosimetry and toxicology) of the new subtype specific nicotinic receptor ligand
(-)-[18F]NCFHEB and to approve this radiotracer in a clinical study comprising healthy controls and AD patients. The final aim of the study is to obtain an accurate marker of nicotinic acetylcholine receptors in a routine clinical setting.

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Organizational Data

  •   DRKS00000472
  •   2010/08/02
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  •   yes
  •   Approved
  •   270-09-ff-14122009, Ethikkommission an der Medizinischen Fakultät der Universität Leipzig
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Secondary IDs

  •   U1111-1115-6970 
  •   2009-012408-26 
  •   4035891 
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Health Condition or Problem studied

  •   G30 -  Alzheimer's disease
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Interventions/Observational Groups

  •   Administration of an intravenous bolus of (-)-[18F]NCFHEB (500 MBq) with subsequent neuronal body PET-Scan in volunteers presenting with mild Alzheimer's disease
  •   Administration of an intravenous bolus of (-)-[18F]NCFHEB (500 MBq) with subsequent neuronal body PET-Scan in healthy volunteers
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Characteristics

  •   Interventional
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  •   Non-randomized controlled trial
  •   Open (masking not used)
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  •   Other
  •   Diagnostic
  •   Other
  •   I
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Primary Outcome

Validation of (-)-[18F]NCFHEB as an in vivo marker of brain α4β2 nicotinic receptor (nAChR) availability in patients with mild Alzheimer’s disease (AD) compared with controls (healthy volunteers). The hypothesis is that nAChR availability is reduced in AD patients compared to healthy volunteers in brain regions primarely affected in AD such as temporo-parietal and posterior cingulate cortices.

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Secondary Outcome

1. To demonstrate the correlation of reduced α4β2 nAChRs availability and cognitive declines at one-year follow-up in patients with mild AD
2. Determination of safety and tolerability of (-)-[18F]NCFHEB
3. Determination of the pharmacokinetic parameters and exposure to radiation by (-)-[18F]NCFHEB
4. Development of a kinetic model in order to quantitatively describe regional central α4β2 nAChR availability in the brain of patients with AD, as well as healthy volunteers

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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Recruitment

  •   Actual
  •   2010/08/30
  •   43
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   55   Years
  •   no maximum age
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Additional Inclusion Criteria

Healthy volunteers:
1 Males/females aged greater than or equal to 55 years of age, females must be without childbearing potential (confirmed by either: age ≥ 60; or history of hysterectomy; or hormone analysis in serum: Estradiol ≤ 20 pg/mL and follicle stimulating hormone (FSH) ≥ 40 IU/L, or last spontaneous bleeding at least 2 years prior to the study start)
2 Able to understand the information provided on purpose and conduct of the clinical study
3 Have signed the informed consent to participate in the study
4 No history of any psychiatric or neurological diseases. Clinical Dementia Rating (CDR) score of 0 (zero) and psychometric test results lying within an interval of one standard deviation from the mean value (mean value and standard deviations adjusted for age and education), for all subtests of the test battery applied.
5 Brain MRI: medial temporal lobe atrophy (MTA) score ≤ 2 on the Scheltens scale 54 (scale ranging from 0 to 4)
6 Brain MRI: white matter lesion (WML) score ≤ 2 on the Fazekas scale 15 (scale ranging from 0 to 3)
7 Adequate visual and auditory acuity to complete neuropsychological testing, as assessed by the recruiting investigator

AD patients
1 Males/females aged greater than or equal to 55 years of age; females must be without childbearing potential (confirmed by either: age ≥ 60; or history of hysterectomy; or hormone analysis in serum: Estradiol ≤ 20 pg/mL and follicle stimulating hormone FSH ≥ 40 IU/L, or last spontaneous bleeding at least 2 years prior to the study start)
2 Capable of understanding the information provided on purpose and conduct of the clinical study and able to give meaningful informed consent by himself / herself
3 Have signed the informed consent to participate in the study
4 Adequate visual and auditory acuity to complete neuropsychological testing, as assessed by the recruiting investigator
5 AD patients, characterized by:
a) Progressive cognitive decline with DSM-IV criteria for Dementia
b) Probable Alzheimer Disease according to the NINCDS-ARDA criteria
c) Severity of dementia: mild, with a score of 1 on the Clinical Dementia Rating (CDR) and 18-26 on the Mini Mental State Examination (MMSE)

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Exclusion Criteria

Healthy volunteers
1 Clinical significant abnormal physical examination
2 Evidence of any significant psychiatric or neurological illness from history, clinical or para – clinical findings
3 History, physical or imaging findings of any significant neurological illness such as cerebrovascular disease, inflammatory or infectious disease and other neurodegenerative diseases
4 Grossly pathological findings in brain MRI

AD patients
1 History, physical or imaging findings of other neurological illness apart from AD such as cerebrovascular disease, inflammatory or infectious disease and other degenerative diseases or other dementia types such as fronto-temporal lobe dementia or Lewy body disease.
2 Use of cholinesterase inhibitors.

All subjects
1 Previous significant occupational exposure to ionizing radiation or in whom, within the last 10 years, radioactive substances were applied for the purposes of research.
2 Hematological or biochemical parameters that are outside the normal range and are considered clinically significant by the investigator.
3 History of alcohol or drug abuse/dependence
4 History of major allergic reactions
5 History of epilepsy
6 History of electroconvulsive therapy
7 Any significant disease or unstable medical condition (e.g. unstable angina, myocardial infarction or coronary revascularization in the preceding 12 months, cardiac failure, chronic renal failure, chronic hepatic disease, severe pulmonary disease, blood disorders, poorly controlled diabetes, chronic infection)
8 Criteria which in the opinion of the investigator preclude participation for scientific reasons, for reasons of compliance, or for reasons of the volunteer’s safety
9 Participants in whom magnetic resonance imaging (MRI) is contraindicated.
10 Patient / Volunteer is in custody by order of an authority or a court of law
11 Exclusion periods from other studies or simultaneous participation in other clinical studies
12 Patient / Volunteer has received another investigational drug in the preceding 2 months
13 Previous enrollment in this study
14 Active Smokers

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Addresses

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    • Universität Leipzig
    • Ritterstr. 26
    • 04109  Leipzig
    • Germany
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    • Universität Leipzig Zentrum für klinische Studien Leipzig - KKS
    • Ms.  Dr. rer. nat.  Petra  Neuhaus 
    • Härtelstr. 16-18
    • 04107  Leipzig
    • Germany
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    • Universitätsklinikum Leipzig AöR Dep. of Nuclear Medicine
    • Mr.  Prof. Dr.  Osama  Sabri 
    • Liebigstraße 18
    • D-04103  Leipzig
    • Germany
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Sources of Monetary or Material Support

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    • Bundesministerium für Bildung und Forschung - BMBF Dienstsitz Berlin
    • Hannoversche Straße 28-30
    • 10115  Berlin
    • Germany
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    •   +49 (0)30/ 1857-0
    •   +49 (0)30/ 1857-83601
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Status

  •   Recruiting complete, follow-up complete
  •   2013/01/24
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Trial Publications, Results and other Documents

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