Clinical trial NCT00970333: Evaluation of [18F] FEPPA and PET Imaging as a Marker of Inflammation in Subjects With Neurological Conditions
Official title: Evaluation of [18F] FEPPA and PET as a Marker of Inflammation in Subjects With Neurological Conditions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer Disease
Parkinson Disease
Multiple Sclerosis
Keywords: Alzheimer disease
Parkinson disease
Multiple Sclerosis
Lead sponsor: Institute for Neurodegenerative Disorders
Sponsor class: OTHER
First posted: 2009-09-02
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Ultimately a marker of microglial activation could be used for large-scale quantitative brain imaging trials in Alzheimer Disease (AD), Parkinson Disease (PD) or Multiple Sclerosis (MS), specifically to investigate the agent as an objective biomarker in treatments aimed at reducing inflammatory changes in these conditions. The significance of this work lies in applying state-of-art quantitative neuroimaging tools to develop a relevant biomarker in individuals with neurodegenerative diseases with the intention of using this efficiently in large clinical imaging trials.

Detailed description: The adaptation of imaging agents like \[18F\]-FEPPA as a biomarker of microglial activation in neurodegenerative and neuroinflammatory diseases requires human validation studies. Expanding upon our previous work with B-amyloid ligands (123I-IMPY, 123I MNI-187) for AD and dopamine transporter ligands (123I B-CIT, Altropane) for PD, we desire to develop and characterize \[18F\]-FEPPA as a potential marker for microglial activation in association with neuronal damage that may be applicable to multiple neurodegenerative and inflammatory diseases.

Eligibility criteria: Inclusion Criteria:

* Alzheimer's disease patients will be recruited for this study. The following criteria will be met for inclusion of AD subjects in this study:

  * The participant is 50 years or older.
  * Written informed consent is obtained.
  * Participants have a clinical diagnosis of probable Alzheimer's disease based on National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria.
  * Clinical Dementia Rating Scale score ≤ 2.
  * Modified Hachinski Ischemia Scale score of ≤ 4.
  * For females, non-child bearing potential or a negative urine or blood pregnancy test on day of \[18F\]-FEPPA injection.

Exclusion Criteria:

* Alzheimer's subjects will be excluded from participation for the following reasons:

  * The subject has a history of significant cerebrovascular disease.
  * The subject has a clinically significant abnormal laboratory value and/or clinically significant unstable medical or psychiatric illness
  * The subject has evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency, pulmonary, or other disorder or disease.
  * Pregnancy

Inclusion Criteria:

* The following criteria will be met for inclusion of PD subjects in this study:

  * The participant is 30 years or older.
  * Written informed consent is obtained.
  * Participants have a clinical diagnosis of Parkinson disease (at least two of the three cardinal symptoms: resting tremor, rigidity, bradykinesia).
  * Hoehn and Yahr ≤4.
  * For females, non-child bearing potential or a negative urine or blood pregnancy test on day of \[18F\]-FEPPA injection.

Exclusion Criteria:

* Parkinson's subjects will be excluded from participation for the following reasons:

  * The subject has a clinically significant abnormal laboratory value and/or clinically significant unstable medical or psychiatric illness
  * The subject has evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency, pulmonary, or other disorder or disease.
  * Pregnancy

Inclusion Criteria:

* Multiple Sclerosis Subject Selection. Subjects who have a clinical diagnosis of Multiple Sclerosis (MS) will be recruited for this study. The following criteria will be met for inclusion of MS subjects in this study:

  * The participant is 18 years or older.
  * Written informed consent is obtained.
  * Participants have a clinical diagnosis of Multiple Sclerosis (per the 2005 Revised McDonald Criteria; Polman, et al., 2005).
  * Kurtzke Expanded Disability Status Scale (EDSS) ≤ 7.5.
  * For females, non-child bearing potential or a negative urine or blood pregnancy test on day of \[18F\]-FEPPA injection.

Exclusion Criteria:

* MS subjects will be excluded from participation for the following reasons:

  * The subject has a clinically significant abnormal laboratory value and/or clinically significant unstable medical or psychiatric illness
  * The subject has evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency, pulmonary, or other disorder or disease.
  * Pregnancy

Primary outcomes:
measure: The primary imaging outcome measure will be the brain regional distribution volumes expressed as a brain tissue to plasma ratio of the radioligand, [18F]-FEPPA.
timeFrame: one year
Secondary outcomes:
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Instiute for Neurodegenerative Disorders
state: Connecticut
Study officials:
affiliation: Institute for Neurodegenerative Disorders
name: Danna Jennings, MD
role: PRINCIPAL_INVESTIGATOR
References: