Ignite Creation Date:
2024-05-06 @ 8:27 AM
Last Modification Date:
2024-10-26 @ 12:00 PM
Study NCT ID:
NCT02743377
Status:
COMPLETED
Last Update Posted:
2020-10-19
First Post:
2016-04-15
Brief Title:
PET Imaging of Phosphodiesterase-4 PDE4 in Brain and Peripheral Organs of McCune-Albright Syndrome
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
PET Imaging of Phosphodiesterase-4 PDE4 in Brain and Peripheral Organs of Mccune-Albright Syndrome
Status:
COMPLETED
Status Verified Date:
2020-05-19
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 11CR-rolipram will be given through an intravenous tube
Participants will have a brain PET scan with 11CR-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 11CR-rolipram will be given through an intravenous tube
Participants will have a brain PET scan with 11CR-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
Detailed Description:
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 11CR-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 about 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 venous 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
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 about 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 venous 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 16-M-0093 | None | None | None |