PET Imaging of Phosphodiesterase-4 (PDE4) in Brain and Peripheral Organs of McCune-Albright Syndrome
| Status: | Recruiting |
|---|---|
| Conditions: | Other Indications, Neurology |
| Therapuetic Areas: | Neurology, Other |
| Healthy: | No |
| Age Range: | 18 - 100 |
| Updated: | 7/1/2018 |
| Start Date: | April 15, 2016 |
| End Date: | March 25, 2020 |
| Contact: | Holly Giesen |
| Email: | giesenh@mail.nih.gov |
| Phone: | (301) 435-8982 |
PET Imaging of Phosphodiesterase-4 (PDE4) in Brain and Peripheral Organs of Mccune-Albright Syndrome
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 slides in and out of a scanner. They may
wear a plastic mask to hold their head in place. They will have blood drawn.
Participants with MAS will be interviewed about their thinking and mood. They may complete
questionnaires about how they feel or think.
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 slides in and out of a scanner. They may
wear a plastic mask to hold their head in place. They will have blood drawn.
Participants with MAS will be interviewed about their thinking and mood. They may complete
questionnaires about how they feel or think.
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: Alison M. Boyce, 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 individual differences
in metabolism of the radioligand or regional blood flow in brain. The secondary outcome
measure will be obtained in whole body scans as area under the curve (AUC) of radioactivity
expressed as standard uptake value (SUV). SUV is calculated by normalizing radioactivity in
PET images to injection activity and body weight. Vt in brain will be compared between
subjects with MAS and healthy controls. AUC will be compared within-subjects with MAS between
areas of craniofacial fibrous dysplasia and adjacent unaffected bone. AUC of whole body scans
will also be compared between subjects with MAS and healthy controls. We hypothesize that
subjects with MAS will show greater rolipram binding than healthy controls in brain regions,
as well as greater rolipram uptake in bones affected by fibrous dysplasia than in unaffected
bones.
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: Alison M. Boyce, 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 individual differences
in metabolism of the radioligand or regional blood flow in brain. The secondary outcome
measure will be obtained in whole body scans as area under the curve (AUC) of radioactivity
expressed as standard uptake value (SUV). SUV is calculated by normalizing radioactivity in
PET images to injection activity and body weight. Vt in brain will be compared between
subjects with MAS and healthy controls. AUC will be compared within-subjects with MAS between
areas of craniofacial fibrous dysplasia and adjacent unaffected bone. AUC of whole body scans
will also be compared between subjects with MAS and healthy controls. We hypothesize that
subjects with MAS will show greater rolipram binding than healthy controls in brain regions,
as well as greater rolipram uptake in bones affected by fibrous dysplasia than in unaffected
bones.
- INCLUSION CRITERIA:
Subjects with MAS:
- At least 18 years of age
- Able to provide self-consent
- Diagnosed with MAS under 98-D-0145.
- Have craniofacial fibrous dysplasia and neuropsychological symptoms
Healthy Subjects:
- At least 18 years of age.
- Healthy based on medical history and physical examination.
EXCLUSION CRITERIA:
Subjects with MAS:
- Serious medical conditions, which may interfere with study procedures. Such conditions
include but not limited to significant bone abnormalities in wrist areas of both arms,
which makes it difficult to place a radial arterial line, clinically marked
dysfunction of liver or kidney, which may delay clearance of [(11)C](R)-rolipram.
- Clinically significant laboratory abnormalities not linked to endocrine abnormalities
but that may interfere with the PET measurement or affect safety of the participant
during this study.
- Positive HIV test.
- Head trauma resulting in a period of unconsciousness lasting longer than one hour.
- Metallic foreign bodies that would be affected by the magnetic resonance imaging (MRI)
magnet, or fear of enclosed spaces likely to make the subject unable to undergo an MRI
scan.
- Recent research-related exposure to radiation (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 about two and a half hours.
- Pregnancy or breastfeeding.
- Current substance use disorder based on DSM-5.
- NIMH employees/staff and their immediate family members will be excluded from the
study per NIMH policy.
Healthy Subjects:
- Serious medical conditions, which may interfere with study procedures. Such conditions
include but not limited to clinically marked dysfunction of liver or kidney, which may
delay clearance of [(11)C](R)-rolipram.
- Clinically significant laboratory abnormalities that may interfere with the PET
measurement or affect safety of the participant during this study.
- Personal history of any DSM-5 diagnoses Axis I disorder.
- Positive HIV test.
- Head trauma resulting in a period of unconsciousness lasting longer than one hour.
- Metallic foreign bodies that would be affected by the MRI magnet, or fear of enclosed
spaces likely to make the subject unable to undergo an MRI scan.
- Recent research-related exposure to radiation (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 about two and a half hours.
- Pregnancy or breastfeeding.
- Current substance use disorder based on DSM-5.
- NIMH employees/staff and their immediate family members will be excluded from the
study per NIMH policy.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
301-496-2563
Phone: 800-411-1222
National Institutes of Health Clinical Center The National Institutes of Health (NIH) Clinical Center in...
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