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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03030391
• Other study ID #: 170041
• Secondary ID: 17-M-0041
• Status: Terminated
• Phase: Phase 1
• Start date: January 10, 2017
• Est. completion date: March 16, 2018

Study information

• Verified date: March 16, 2018
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: March 16, 2018
• Est. primary completion date: March 16, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

• 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.

Related Conditions & MeSH terms

• Healthy

Intervention

Other:
• PET

• MRI

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quantification of 18F-PF-06445974 binding in brain		2 hours
Secondary	Biodistribution of 18F-PF-06445974 in the body.		2 hours