Evaluation of a Novel PET Radioligand for Phosphodiesterase-4D (PDE4D)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Whole Brain Total Distribution Volume (VT)-1st Blocked
研究概览
简要总结
Background:
The brain enzyme phosphodiesterase-4D (PDE4D) may affect thinking and depression. Drugs with some radioactivity can attach to enzymes and be seen on a scan. Researchers want to test a new radioactive drug, 11C-T-1650, to measure PDE4D in the brain and body. They also want to see if the new drug BPN14770 blocks 11C-T-1650 from the brain. They want to learn more about psychiatric disorders and possible treatments.
Objectives:
To study how well 11C-T-1650 helps show PDE4D on a scan and to see if BPN14770 blocks it.
Eligibility:
Healthy adults at least 18 years old
Design:
Participants will be screened in other protocols.
Some participants will have 1 body PET scan.
Some participants will have 2 brain PET scans and 1 brain MRI within 1 year.
Some participants (ages 18 55) will:
Have 3 brain PET scans and 1 MRI
Take BPN14770 by mouth twice daily for 3 7 days
Have blood and urine tests
Have a follow-up physical exam and heart test
PET (positron emission tomography) scans will take 2 3 hours. Participants will:
Have a thin plastic tube (catheter) placed in an arm vein by needle.
Get a small amount of 11C-T-1650 injected via catheter. Another catheter may be placed to draw blood.
Lie quietly on a bed that slides into a donut-shaped scanner without sleeping. They may get a short break.
Have heart and vital signs monitored.
Have blood and urine tests.
Learn about drinking fluids and urinating after the scan
MRI (magnetic resonance imagining) scans will take 30 60 minutes:
Participants will lie on a table that slides into a metal cylinder in a magnetic field.
Sponsoring Institute: National Institute of Mental Health
...
详细描述
Objective
Phosphodiesterase type 4 (PDE4) metabolizes 3 <=,5 <=-cyclic adenosine monophosphate (cAMP), thereby terminating this second messenger. PDE4 is selective to cAMP over cyclic guanosine monophosphate. PDE4 has four isozymes A, B, C, and D and basic studies suggest that type D (PDE4D) may play a key role in cognitive function and depression. That is, PDE4D inhibitors are expected to improve cognitive function and depressive symptoms.
In collaboration with Tetra Discovery Partners, we have developed a PET ligand, 11C-T-1650, to selectively image PDE4D. This type D selective ligand was developed based on 3D structural differences between PDE4D and PDE4 type B (PDE4B) Our PET studies using 11C-T-1650 in nonhuman primate have shown promising results, and we now seek to evaluate it in in healthy subjects.
This study has three primary objectives. First, we will determine whether the uptake of 11C-T-1650 in the brain reflects the distribution of PDE4D, as demonstrated by blocking with a PDE4D selective compound BPN14770, being developed by Tetra Discovery Partners for treating cognitive disorders including depression. Second, we will measure binding site occupancy of BPN14770 administered at doses that may be used in clinical trials. Third, we will measure the test/retest reproducibility of brain uptake quantified by kinetic modeling and using arterial blood samples.
Study Population
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Whole body PET Scan with intravenous 11C-T-1650
10 mCi of 11C-T-1650 given intravenously once followed by a Whole Body PET scan. This was done for whole body dosimetry calculations.
干预措施: [C-11]T-1650 (Drug)
Brain PET scan with 11C-T-1650 and blocking with BPN14770
Baseline brain PET scan (scan 1) with 20 mCi of 11C-T-1650 given intravenously, followed by a second Brain PET scan (scan 2) 90-180 minutes after first dose administration of BPN14770 50mg given orally. A third brain PET scan (scan 3) is performed after the last dose of BPN14770. 20 mCi of 11C-T-1650 is given intravenously with each PET scan. BPN14770 50mg given orally twice a day for a total of seven doses. BPN14770 is a PDE4D-inhibitor.
干预措施: [C-11]T-1650 (Drug)
Brain PET scan with 11C-T-1650 and blocking with BPN14770
Baseline brain PET scan (scan 1) with 20 mCi of 11C-T-1650 given intravenously, followed by a second Brain PET scan (scan 2) 90-180 minutes after first dose administration of BPN14770 50mg given orally. A third brain PET scan (scan 3) is performed after the last dose of BPN14770. 20 mCi of 11C-T-1650 is given intravenously with each PET scan. BPN14770 50mg given orally twice a day for a total of seven doses. BPN14770 is a PDE4D-inhibitor.
干预措施: BPN14770 (Drug)
结局指标
主要结局
Whole Brain Total Distribution Volume (VT)-1st Blocked
时间窗: 120 minutes after the start of the second scan
To determine whether the uptake of 11C-T-1650 in brain reflects the distribution of PDE4D
Whole Brain Total Distribution Volume (VT) - Baseline
时间窗: 120 minutes after the start of the first scan
To determine whether the uptake of 11C-T-1650 in brain reflects the distribution of PDE4D
Standard UptakeValue (SUV) Area Under the Curve (AUC) (60-120min)-Baseline Whole Brain
时间窗: 120 minutes after the start of the scan
Measure binding site occupancy of BPN14770 administered at doses that may be used in clinical trials.
Standard UptakeValue (SUV) Area Under the Curve (AUC) (60-120min)-1st Blocked Whole Brain
时间窗: 120 minutes after the start of the first scan
Measure binding site occupancy of BPN14770 administered at doses that may be used in clinical trials.
Standard UptakeValue (SUV) Area Under the Curve (AUC) (60-120min)-2nd Blocked Whole Brain
时间窗: 120 minutes after the start of the first scan
Measure binding site occupancy of BPN14770 administered at doses that may be used in clinical trials.
次要结局
未报告次要终点