PET Imaging of Phosphodiesterase-4 (PDE4) in Brain and Peripheral Organs of McCune-Albright Syndrome

NCT02743377 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 16009316-M-0093
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Nervous System Disease

Keywords

GsI+/-; Camp; GNAS

Outcome Measures

Primary Outcomes (11)

• Standard UptakeValue (SUV) Area Under the Curve (AUC) (30-120min) - Bladder

  Determine if there is a difference in PDE4 levels (measured using \[11C\]rolipram) in the periphery of patients with McCune-Albright Syndrome (MAS) compared to healthy controls.

  120 minutes

• Standard UptakeValue (SUV) Area Under the Curve (AUC) (30-120min) -Gallbladder

  Determine if there is a difference in PDE4 levels (measured using \[11C\]rolipram) in the periphery of patients with McCune-Albright Syndrome (MAS) compared to healthy controls.

  120 minutes

• Standard UptakeValue (SUV) Area Under the Curve (AUC) (30-120min) - Heart

  Determine if there is a difference in PDE4 levels (measured using \[11C\]rolipram) in the periphery of patients with McCune-Albright Syndrome (MAS) compared to healthy controls.

  120 minutes

• Standard UptakeValue (SUV) Area Under the Curve (AUC) (30-120min) - Kidneys

  Determine if there is a difference in PDE4 levels (measured using \[11C\]rolipram) in the periphery of patients with McCune-Albright Syndrome (MAS) compared to healthy controls.

  120 minutes

• Standard UptakeValue (SUV) Area Under the Curve (AUC) (30-120min) - Liver

  Determine if there is a difference in PDE4 levels (measured using \[11C\]rolipram) in the periphery of patients with McCune-Albright Syndrome (MAS) compared to healthy controls

  120 minutes

• Standard UptakeValue (SUV) Area Under the Curve (AUC) (30-120min) - Lungs

  Determine if there is a difference in PDE4 levels (measured using \[11C\]rolipram) in the periphery of patients with McCune-Albright Syndrome (MAS) compared to healthy controls

  120 minutes

• Standard UptakeValue (SUV) Area Under the Curve (AUC) (30-120min) -Spleen

  Determine if there is a difference in PDE4 levels (measured using \[11C\]rolipram) in the periphery of patients with McCune-Albright Syndrome (MAS) compared to healthy controls

  120 minutes

• Standard UptakeValue (SUV) Area Under the Curve (AUC) (30-120min) - Stomach

  Determine if there is a difference in PDE4 levels (measured using \[11C\]rolipram) in the periphery of patients with McCune-Albright Syndrome (MAS) compared to healthy controls

  120 minutes

• Whole Brain Total Distribution Volume (VT)

  Determine if there is a difference in PDE4 levels (measured using \[11C\]rolipram) in the brain of patients with McCune-Albright Syndrome (MAS) compared to healthy controls

  90 minutes

• MAS Affected Bone SUV AUC(60-120min) at Baseline

  To assess whether uptake in dysplastic bone reflects parent radioligand binding to the enzyme or merely accumulation of radiometabolites

  120 minutes

• MAS Affected Bone SUV AUC(60-120min) - Blocked

  To assess whether uptake in dysplastic bone reflects parent radioligand binding to the enzyme or merely accumulation of radiometabolites

  120 minutes

Secondary Outcomes (2)

• MAS Affected Bone SUV AUC(60-120min) - for Baseline and Blocked Subjects With MAS

  120 minutes

• Normal Bone SUV AUC (60-120min) - for Healthy Controls

  120 minutes after the start of the scan

Study Arms (2)

Subjects with McCune-Albright syndrome (MAS)

EXPERIMENTAL

Subjects with McCune-Albright syndrome (MAS) who received 11C-(R)-rolipram whole-body and/or brain PET scans

Other: Brain PET Imaging with 11C Rolipram; Drug: Whole Body PET Baseline with 11C Rolipram; Drug: Whole Body PET Blocked with Roflumilast

Healthy control

EXPERIMENTAL

Healthy control received 11C-(R)-rolipram whole-body and/or brain PET scans

Other: Brain PET Imaging with 11C Rolipram; Drug: Whole Body PET Baseline with 11C Rolipram

Interventions

Brain PET Imaging with 11C Rolipram OTHER

Brain PET Imaging, single scan, with 11C Rolipram 20 mCi given intravenously at the start of the scan

Healthy control; Subjects with McCune-Albright syndrome (MAS)

Whole Body PET Baseline with 11C Rolipram DRUG

Whole Body Baseline PET Imaging, single scan, with 11C Rolipram 20 mCi given intravenously at the start of the scan

Healthy control; Subjects with McCune-Albright syndrome (MAS)

Whole Body PET Blocked with Roflumilast DRUG

Whole Body PET Imaging scan after blockade with Roflumilast 500 mcg PO, given 1-2 hours prior to start of scan

Subjects with McCune-Albright syndrome (MAS)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Healthy Subjects:
• At least 18 years of age.
• Healthy based on medical history and physical examination.

You may not qualify if:

• 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.
• 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 Axis I disorder.
• Positive HIV test.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Nervous System Diseases; Muscle Cramp

Interventions

Roflumilast

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr Robert Innis
• Organization: National Institute of Mental Health

innisr@mail.nih.gov

+1 301 693 2979

Study Officials

• Robert B Innis, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2016
• First Posted: April 19, 2016
• Study Start: April 4, 2018
• Primary Completion: October 23, 2019
• Study Completion: May 19, 2020
• Last Updated: October 19, 2020
• Results First Posted: October 19, 2020

Record last verified: 2020-05-19

Locations

US (1)