Clinical Trial: PET Imaging of Phosphodiesterase-4 (PDE4) in Brain and Peripheral Organs of McCune-Albright Syndrome
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: PET Imaging of Phosphodiesterase-4 (PDE4) in Brain and Peripheral Organs of Mccune-Albright Syndrome
Brief Summary:
Background:
McCune-Albright Syndrome (MAS) is a disorder that affects the bones, skin, and some hormone-producing tissues. It is associated with a mutation in a gene. This gene affects enzymes in the brain and body. Researchers want to learn more about one of these enzymes, Phosphodiesterase 4 (PDE4), in people with MAS.
Objective:
To see if people with MAS have higher levels of PDE4 than people without MAS.
Eligibility:
People ages 18 and older who have MAS and participated in protocol 98-D-0145, Screening and Natural History of Patients with Polyostotic Fibrous Dysplasia and the McCune-Albright Syndrome. Healthy adult volunteers are also needed.
Design:
This study requires 1 to 4 outpatient visits to the NIH Clinical Center. Some visits may take place on the same day.
Participants with MAS will be screened with medical history and physical exam. They will have blood and urine tests.
Participants will have a magnetic resonance imaging scan.
Participants will have a full body positron emission tomography (PET) scan. A small amount of a radioactive chemical, [11C](R)-rolipram, will be given through an intravenous tube.
Participants will have a brain PET scan with [11C](R)-rolipram. For this, a thin plastic tube will also be put into an artery at their wrist or elbow crease area.
For the scans, participants will lie on a bed that slid
Detailed Summary:
Objective: McCune-Albright syndrome (MAS) is a mosaic disease arising from early embryonic somatic activating mutations of GNAS, which encodes the 3 <=, 5 <=-cyclic adenosine monophosphate (cAMP) pathway-associated G-protein, Gs . Constitutive activation of Gs leads to increased cAMP signaling in brain, as well as in peripheral organs, particularly bones. Although subjects with MAS show psychiatric and neurological symptoms, few studies have attempted to assess brain changes in these individuals. This protocol seeks to study changes in the cAMP cascade both in brain and peripheral organs of individuals with MAS using [11C](R)-rolipram PET, which binds to phosphodiesterase 4 (PDE4) and reflects cAMP cascade activity.
Study population: Participants will include 20 subjects with MAS and 15 healthy subjects group-matched to MAS subjects for age and gender. Both MAS subjects and healthy controls will have one or two PET scans: one whole body and one brain scan. We expect 10 brain and 10 whole body scan to be performed in each group.
Design: Subjects with MAS will be recruited from participants in 98-D-0145 Screening and Natural History of Patients with Polyostotic Fibrous Dysplasia and the McCune-Albright Syndrome (PI: Michael T. Collins, MD). Only participants in protocol (98-D-0145) who provided self-consent without a legally authorized representative will be recruited. Brain PET scans will be performed by measuring metabolite-corrected arterial input function. No blood sampling will be performed for whole body scans.
Outcome measures: The primary outcome measure will be obtained in brain scans as the amount of radioligand binding quantified as distribution volume (Vt). Calculated from both brain and plasma data, Vt reflects rolipram binding to PDE4, corrected for any in
Sponsor: National Institute of Mental Health (NIMH)
Current Primary Outcome: Rolipram binding in brain [ Time Frame: Ongoing ]
Original Primary Outcome: Same as current
Current Secondary Outcome: Rolipram uptake in peripheral organs [ Time Frame: Ongoing ]
Original Secondary Outcome: Same as current
Information By: National Institutes of Health Clinical Center (CC)
Dates:
Date Received: April 15, 2016
Date Started: April 4, 2016
Date Completion: March 25, 2020
Last Updated: May 12, 2017
Last Verified: April 18, 2017
