Trial Outcomes & Findings for PET Imaging of Phosphodiesterase-4 (PDE4) in Brain and Peripheral Organs of McCune-Albright Syndrome (NCT NCT02743377)

NCT ID: NCT02743377

Last Updated: 2020-10-19

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 16 participants
• Primary outcome timeframe: 120 minutes
• Results posted on: 2020-10-19

Participant Flow

16 subjects were enrolled but one subject did not start the study.

Participant milestones

Measure	Healthy Control Healthy controls received 11C-(R)-rolipram whole-body and/or brain PET scans	Subjects With McCune-Albright Syndrome (MAS) Subjects with McCune-Albright syndrome (MAS) who received 11C-(R)-rolipram whole-body and/or brain PET scans
Overall Study STARTED	9	6
Overall Study Brain PET With 11C Rolipram	8	3
Overall Study Whole Body PET Baseline With 11C Rolipra	5	4
Overall Study Whole Body PET Baseline & Blocked	0	2
Overall Study COMPLETED	7	6
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Healthy Control n=9 Participants Healthy controls received 11C-(R)-rolipram whole-body and/or brain PET scans	Subjects With McCune-Albright Syndrome (MAS) n=6 Participants Subjects with McCune-Albright syndrome (MAS) who received 11C-(R)-rolipram whole-body and/or brain PET scans	Total n=15 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=93 Participants	6 Participants n=4 Participants	15 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Sex: Female, Male Female	7 Participants n=93 Participants	5 Participants n=4 Participants	12 Participants n=27 Participants
Sex: Female, Male Male	2 Participants n=93 Participants	1 Participants n=4 Participants	3 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=93 Participants	6 Participants n=4 Participants	15 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	4 Participants n=93 Participants	0 Participants n=4 Participants	4 Participants n=27 Participants
Race (NIH/OMB) White	3 Participants n=93 Participants	6 Participants n=4 Participants	9 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants

PRIMARY outcome

Timeframe: 120 minutes

Population: Subjects who completed whole body scan with 11-C Rolipram

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.

Outcome measures

Measure	Healthy Control n=5 Participants Healthy control received 11C-(R)-rolipram whole-body and/or brain PET scans	Subjects With McCune-Albright Syndrome (MAS) n=4 Participants Subjects with McCune-Albright syndrome (MAS) who received 11C-(R)-rolipram whole-body and/or brain PET scans
Standard UptakeValue (SUV) Area Under the Curve (AUC) (30-120min) - Bladder	575.1 SUV x min Standard Deviation 402.2	650.8 SUV x min Standard Deviation 344.7

PRIMARY outcome

Timeframe: 120 minutes

Population: Subjects who completed whole body scan with 11-C Rolipram

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.

Outcome measures

Measure	Healthy Control n=5 Participants Healthy control received 11C-(R)-rolipram whole-body and/or brain PET scans	Subjects With McCune-Albright Syndrome (MAS) n=4 Participants Subjects with McCune-Albright syndrome (MAS) who received 11C-(R)-rolipram whole-body and/or brain PET scans
Standard UptakeValue (SUV) Area Under the Curve (AUC) (30-120min) -Gallbladder	581.2 SUV x min Standard Deviation 235.8	417.9 SUV x min Standard Deviation 317.8

PRIMARY outcome

Timeframe: 120 minutes

Population: Subjects who completed whole body scan with 11-C Rolipram

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.

Outcome measures

Measure	Healthy Control n=5 Participants Healthy control received 11C-(R)-rolipram whole-body and/or brain PET scans	Subjects With McCune-Albright Syndrome (MAS) n=4 Participants Subjects with McCune-Albright syndrome (MAS) who received 11C-(R)-rolipram whole-body and/or brain PET scans
Standard UptakeValue (SUV) Area Under the Curve (AUC) (30-120min) - Heart	27.4 SUV x min Standard Deviation 6.1	25.4 SUV x min Standard Deviation 5.8

PRIMARY outcome

Timeframe: 120 minutes

Population: Subjects who completed whole body scan with 11-C Rolipram

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.

Outcome measures

Measure	Healthy Control n=5 Participants Healthy control received 11C-(R)-rolipram whole-body and/or brain PET scans	Subjects With McCune-Albright Syndrome (MAS) n=4 Participants Subjects with McCune-Albright syndrome (MAS) who received 11C-(R)-rolipram whole-body and/or brain PET scans
Standard UptakeValue (SUV) Area Under the Curve (AUC) (30-120min) - Kidneys	63.3 SUV x min Standard Deviation 14.8	80.4 SUV x min Standard Deviation 12.4

PRIMARY outcome

Timeframe: 120 minutes

Population: Subjects who completed whole body scan with 11-C Rolipram

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

Outcome measures

Measure	Healthy Control n=5 Participants Healthy control received 11C-(R)-rolipram whole-body and/or brain PET scans	Subjects With McCune-Albright Syndrome (MAS) n=4 Participants Subjects with McCune-Albright syndrome (MAS) who received 11C-(R)-rolipram whole-body and/or brain PET scans
Standard UptakeValue (SUV) Area Under the Curve (AUC) (30-120min) - Liver	47.6 SUV x min Standard Deviation 21.7	52.4 SUV x min Standard Deviation 4.4

PRIMARY outcome

Timeframe: 120 minutes

Population: Subjects who completed whole body scan with 11-C Rolipram

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

Outcome measures

Measure	Healthy Control n=5 Participants Healthy control received 11C-(R)-rolipram whole-body and/or brain PET scans	Subjects With McCune-Albright Syndrome (MAS) n=4 Participants Subjects with McCune-Albright syndrome (MAS) who received 11C-(R)-rolipram whole-body and/or brain PET scans
Standard UptakeValue (SUV) Area Under the Curve (AUC) (30-120min) - Lungs	10.2 SUV x min Standard Deviation 4.3	9.6 SUV x min Standard Deviation 4.4

PRIMARY outcome

Timeframe: 120 minutes

Population: Subjects who completed whole body scan with 11-C Rolipram

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

Outcome measures

Measure	Healthy Control n=5 Participants Healthy control received 11C-(R)-rolipram whole-body and/or brain PET scans	Subjects With McCune-Albright Syndrome (MAS) n=4 Participants Subjects with McCune-Albright syndrome (MAS) who received 11C-(R)-rolipram whole-body and/or brain PET scans
Standard UptakeValue (SUV) Area Under the Curve (AUC) (30-120min) -Spleen	20.1 SUV x min Standard Deviation 2.8	18.7 SUV x min Standard Deviation 2.7

PRIMARY outcome

Timeframe: 120 minutes

Population: Subjects who completed whole body scan with 11-C Rolipram

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

Outcome measures

Measure	Healthy Control n=5 Participants Healthy control received 11C-(R)-rolipram whole-body and/or brain PET scans	Subjects With McCune-Albright Syndrome (MAS) n=4 Participants Subjects with McCune-Albright syndrome (MAS) who received 11C-(R)-rolipram whole-body and/or brain PET scans
Standard UptakeValue (SUV) Area Under the Curve (AUC) (30-120min) - Stomach	39.4 SUV x min Standard Deviation 20.8	34.1 SUV x min Standard Deviation 22.8

PRIMARY outcome

Timeframe: 90 minutes

Population: Subjects who completed brain scan with 11-C Rolipram

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

Outcome measures

Measure	Healthy Control n=7 Participants Healthy control received 11C-(R)-rolipram whole-body and/or brain PET scans	Subjects With McCune-Albright Syndrome (MAS) n=3 Participants Subjects with McCune-Albright syndrome (MAS) who received 11C-(R)-rolipram whole-body and/or brain PET scans
Whole Brain Total Distribution Volume (VT)	0.67 mL x cm-3 Standard Deviation 0.08	0.52 mL x cm-3 Standard Deviation 0.06

PRIMARY outcome

Timeframe: 120 minutes

Population: Subjects who completed two whole body scans the first with 11-C Rolipram, and the second blocked with Roflumilast

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

Outcome measures

Measure	Healthy Control n=2 Participants Healthy control received 11C-(R)-rolipram whole-body and/or brain PET scans	Subjects With McCune-Albright Syndrome (MAS) Subjects with McCune-Albright syndrome (MAS) who received 11C-(R)-rolipram whole-body and/or brain PET scans
MAS Affected Bone SUV AUC(60-120min) at Baseline	11.2 SUV x min Standard Deviation 0.66	—

PRIMARY outcome

Timeframe: 120 minutes

Population: Subjects who completed two whole body scans, the first with 11-C Rolipram and the second blocked with Roflumilast

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

Outcome measures

Measure	Healthy Control n=2 Participants Healthy control received 11C-(R)-rolipram whole-body and/or brain PET scans	Subjects With McCune-Albright Syndrome (MAS) Subjects with McCune-Albright syndrome (MAS) who received 11C-(R)-rolipram whole-body and/or brain PET scans
MAS Affected Bone SUV AUC(60-120min) - Blocked	11.1 SUV x min Standard Deviation 0.53	—

SECONDARY outcome

Timeframe: 120 minutes

Population: The analyses included two group of subjects with MAS: subjects who completed a whole body PET scan with 11-C Rolipram and subjects who completed whole body PET scan after blockade with Roflumilast 500 mcg PO

Determine if PDE4 levels are different in areas of fibrous dysplasia as compared to unaffected bones in patients with MAS

Outcome measures

Measure	Healthy Control n=6 Participants Healthy control received 11C-(R)-rolipram whole-body and/or brain PET scans	Subjects With McCune-Albright Syndrome (MAS) Subjects with McCune-Albright syndrome (MAS) who received 11C-(R)-rolipram whole-body and/or brain PET scans
MAS Affected Bone SUV AUC(60-120min) - for Baseline and Blocked Subjects With MAS	13.5 SUV x min Standard Deviation 2	—

SECONDARY outcome

Timeframe: 120 minutes after the start of the scan

Population: Healthy control subjects who completed whole body scan with 11-C Rolipram

Determine if PDE4 levels are different in areas of fibrous dysplasia as compared to unaffected bones in patients with MAS

Outcome measures

Measure	Healthy Control n=5 Participants Healthy control received 11C-(R)-rolipram whole-body and/or brain PET scans	Subjects With McCune-Albright Syndrome (MAS) Subjects with McCune-Albright syndrome (MAS) who received 11C-(R)-rolipram whole-body and/or brain PET scans
Normal Bone SUV AUC (60-120min) - for Healthy Controls	4.2 SUV x min Standard Deviation 3.4	—

Adverse Events

Healthy Control

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Subjects With McCune-Albright Syndrome (MAS)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Healthy Control n=9 participants at risk Healthy control received 11C-(R)-rolipram whole-body and/or brain PET scans	Subjects With McCune-Albright Syndrome (MAS) n=6 participants at risk Subjects with McCune-Albright syndrome (MAS) received 11C-(R)-rolipram whole-body and/or brain PET scans
Musculoskeletal and connective tissue disorders Pain in extremity	11.1% 1/9 • 1 day	0.00% 0/6 • 1 day
Nervous system disorders Headache	11.1% 1/9 • 1 day	0.00% 0/6 • 1 day
Psychiatric disorders Panic attack	11.1% 1/9 • 1 day	0.00% 0/6 • 1 day

Additional Information

Dr Robert Innis

National Institute of Mental Health

Phone: +1 301 693 2979

Email: innisr@mail.nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place