Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Novel Positron Emission Tomography (PET) Radiotracer to Image Phosphodiesterase-4B (PDE4B)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03030391
Recruitment Status : Terminated
First Posted : January 25, 2017
Last Update Posted : December 17, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )

Tracking Information
First Submitted Date  ICMJE January 24, 2017
First Posted Date  ICMJE January 25, 2017
Last Update Posted Date December 17, 2019
Study Start Date  ICMJE January 10, 2017
Actual Primary Completion Date March 16, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 24, 2017)
Quantification of 18F-PF-06445974 binding in brain [ Time Frame: 2 hours ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 24, 2017)
Biodistribution of 18F-PF-06445974 in the body. [ Time Frame: 2 hours ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Novel Positron Emission Tomography (PET) Radiotracer to Image Phosphodiesterase-4B (PDE4B)
Official Title  ICMJE Evaluation of a Novel Positron Emission Tomography (PET) Radiotracer to Image Phosphodiesterase-4B (PDE4B)
Brief Summary

Background:

The new drug 18F-PF-06445974 has a little radioactivity. This can be seen by a positron emission tomography (PET) scan. The drug helps researchers see a protein, PDE4B, in the brain. Looking at PDE4B in the living brain might show how it is involved in psychiatric and neurological disorders. One part of the study will look at how the study drug is distributed in the brain. Another part will study how brain measures vary.

Objectives:

To measure the protein PDE4B in the brain. To test how a new radioactive chemical, 18F-PF-06445974, is distributed in the body.

Eligibility:

Healthy adults ages 18 and older

Design:

Participants will have 1-3 visits over a year. Each will be 2-5 hours.

Women will have a pregnancy test each time.

Detailed Description

Objective:

Phosphodiesterase type 4 (PDE4) terminates signal transduction of guanine nucleotidebinding proteins (G-protein)-coupled receptors by metabolizing the second messenger 3 <=,5 <=- cyclic adenosine monophosphate (cAMP). PDE4 is selective to cAMP over cyclic guanosine monophosphate. PDE4 has four isozymes A, B, C, and D and basic studies indicate that type B (PDE4B) plays a key role in cognitive function and neuroinflammation. Thus, PDE4B inhibitors would be expected to improve cognitive function and have anti-inflammatory effects. Pfizer has developed a new PET ligand, 18F-PF-06445974, to selectively image PDE4B; the ligand has shown promising results in non-human primates.

This protocol covers four phases:

  1. Phase 1: whole body imaging of one subject with a low injection activity of 2 mCi to confirm that no organ has prominently high uptake of 18F-PF-06445974;
  2. Phase 2: kinetic brain imaging with up to 5 mCi injection to quantify PDE4B in brain relative to concurrent measurement of the parent radioligand in arterial plasma;
  3. Phase 3: if 18F-PF-06445974 is successful in Phase 2 in the first couple of subjects, we will estimate the radiation-absorbed doses by performing whole body imaging with 5 mCi injection;
  4. Phase 4: test-retest analysis of brain binding relative to concurrent measurement of the parent radioligand in arterial plasma (5 mCi per scan).

Study Population:

Healthy adult female and male volunteers (n=22, ages 18 or older) will undergo brain imaging. An additional eight healthy volunteers will undergo whole body dosimetry analysis, for a total of 30 healthy volunteers.

Design:

For quantification of 18F-PF-06445974, 22 healthy controls will undergo brain PET imaging using 18F-PF-06445974 and an arterial line. Some of them will have a test-retest scan. Eight additional subjects will have a whole body PET scan for dosimetry. For dosimetry, no arterial line will be used.

Outcome Measures:

To assess quantitation of PDE4B with 18F-PF-06445974, we will primarily use two outcome measures, namely the identifiability and time stability of distribution volume (VT) calculated with compartmental modeling. In the test-retest study, we will calculate the retest

variability. We will assess whole-body biodistribution and dosimetry of 18F-PF-06445974 by calculating doses to organs and effective dose to the body.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Healthy
Intervention  ICMJE
  • Other: PET
  • Other: MRI
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 17, 2018)
5
Original Estimated Enrollment  ICMJE
 (submitted: January 24, 2017)
30
Actual Study Completion Date  ICMJE March 16, 2018
Actual Primary Completion Date March 16, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • INCLUSION CRITERIA:
  • Age 18 or older.
  • Able to give written informed consent.
  • Medically and psychiatrically healthy.
  • Enrolled in 01-M-0254 The Evaluation of Participants with Mood and Anxiety Disorders and Healthy Volunteers (PI: Dr. Carlos Zarate).

EXCLUSION CRITERIA:

  • Any current Axis I diagnosis.
  • Clinically significant laboratory abnormalities
  • Positive HIV test.
  • Unable to have an MRI scan.
  • History of neurologic illness or injury with the potential to affect study data interpretation.
  • Recent exposure to radiation related to research (i.e. PET from other research) that, when combined with this study, would be above the allowable limits.
  • Inability to lie flat on camera bed for at least two hours.
  • Pregnancy or breastfeeding.
  • Current substance use disorder based on DSM-5.
  • Current use of psychiatric medications.
  • NIMH employees/staff and their immediate family members will be excluded from the study per NIMH policy.

Exclusion criteria for the dosimetry subjects are the same as reported above, with the exception of MRI contraindications, because an MRI will not be performed in these subjects.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03030391
Other Study ID Numbers  ICMJE 170041
17-M-0041
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
Study Sponsor  ICMJE National Institute of Mental Health (NIMH)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Masahiro Fujita, M.D. National Institute of Mental Health (NIMH)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date March 16, 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP