Evaluation of a Novel PET Radioligand as an Inflammatory Biomarker in Musculoskeletal Conditions
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Uptake of [11C]MC1 by Organs
研究概览
简要总结
Background:
Inflammation plays a significant role in various disorders that involve neurodegeneration or autoimmune reaction as one of their mechanisms. PET scans can help detect inflammation. Two new drugs may create better PET images.
Objective:
- To see if the drug [11C]MC1 can help image inflammation.
Eligibility:
- People age 18 and older with rheumatoid arthritis or idiopathic inflammatory myopathy (IIM).
- Healthy volunteers enrolled in protocol 01-M-0254 or 17-M-0181 are also needed.
Design:
- Healthy participants will be screened under protocol 01-M-0254 or 17-M-0181.
- Participants with arthritis or IIM will have a screening visit. This will include:
- Medical history
- Physical exam
- Blood and urine tests
- Possible CT or X-ray: A machine will take pictures of the body.
- Healthy participants will have 1 or 2 visits. They may have urine tests. They may take the drug celecoxib by mouth. They will have a PET scan. A small amount of one or both study drugs will be injected through a catheter: A needle will guide a thin plastic tube into an arm vein. Another catheter will draw blood. They will like on a bed that slides into a machine. Their vital signs and heart activity will be measured.
- Participants with arthritis will have up to 2 visits after screening. They may take celecoxib and have PET scans.
- Participants with IIM will have up to 3 visits after screening. At 1 or 2 visits, they will take celecoxib and have PET scans. They will have 1 visit where they have an MRI: They will lie on a table that slides into a machine. The machine takes pictures of the body.
详细描述
I. Objective
18-kDa translocator protein (TSPO) and cyclooxygenase-2 (COX-2) are both implicated in the pathophysiology of various inflammatory disorders, suggesting that both may serve as potential biomarkers of inflammation in brain as well as periphery. Our laboratory recently developed two new radioligands: [11C]ER176 to image TSPO and [11C]MC1 to image COX-2. Using wholebody imaging, this study seeks to determine whether PET imaging using these new radioligands can differentiate two inflammatory conditions-rheumatoid arthritis (RA) and idiopathic inflammatory myopathies (IIM)-from healthy conditions. To determine if [11C]MC1 uptake is specific to COX-2, we will also conduct a blocking study with a selective COX-2 inhibitor (celecoxib) in both [11C]MC1 and [11C]ER176 scans; celecoxib is expected to block uptake of [11C]MC1 but not [11C]ER176. Using brain-dedicated imaging, this seeks to determine whether RA patients and healthy volunteers have specific binding in brain - i.e., uptake that can be blocked celecoxib.
II. Study population
Healthy volunteers (n = 17), patients with RA (n = 15), and patients with IIM (n = 15) will undergo whole-body PET/CT scans. Patients with AxSpA (n=15) will undergo two whole-body PET/MRI scans. In addition, healthy volunteers (n = 22) and patients with RA (n = 12) will have brain-dedicated imaging using [11C]MC1 concurrent with arterial blood sampling. Finally, 15 patients with RA will be imaged during a period of moderate to severe symptoms and after clinically indicated treatment for two to four months. Thus, the entire population will be healthy volunteers (n = 39), patients with RA (n = 42), patients with AxSpA (n=15) and patients with
IIM (n = 15).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Phase 1: Pilot - Whole body scan in health participants
Healthy participants receive about 10 mCi of [11C]MC1 intravenously followed by a whole body PET/CT scan. If radiation dose to selected body organs is within safety limit, Phase 2 of study was initiated
干预措施: 11C-MC1 (Drug)
Phase 1: Pilot - Whole body scan in health participants
Healthy participants receive about 10 mCi of [11C]MC1 intravenously followed by a whole body PET/CT scan. If radiation dose to selected body organs is within safety limit, Phase 2 of study was initiated
干预措施: Positron Emission Tomography (PET)/computed tomography (CT) Scan (Diagnostic Test)
Phase 2: Whole body PET/CT scans in patients
Participants with rheumatoid arthritis (RA), idiopathic inflammatory myopathies (IIM), or axial spondyloarthritis (AXSPA), had a baseline whole body PET/CT scan after about 15 mCi of [11C]MC1 followed by a second whole body PET/CT scan with about 15 mCi of [11C]MC1 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day.
干预措施: 11C-MC1 (Drug)
Phase 2: Whole body PET/CT scans in patients
Participants with rheumatoid arthritis (RA), idiopathic inflammatory myopathies (IIM), or axial spondyloarthritis (AXSPA), had a baseline whole body PET/CT scan after about 15 mCi of [11C]MC1 followed by a second whole body PET/CT scan with about 15 mCi of [11C]MC1 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day.
干预措施: Celecoxib (Drug)
Phase 2: Whole body PET/CT scans in patients
Participants with rheumatoid arthritis (RA), idiopathic inflammatory myopathies (IIM), or axial spondyloarthritis (AXSPA), had a baseline whole body PET/CT scan after about 15 mCi of [11C]MC1 followed by a second whole body PET/CT scan with about 15 mCi of [11C]MC1 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day.
干预措施: Positron Emission Tomography (PET)/computed tomography (CT) Scan (Diagnostic Test)
Phase 2: Whole body PET/CT scans in healthy participants
Healthy participants had a baseline whole body PET/CT scan after receiving about 15 mCi of [11C]MC1 followed by a second whole body PET/CT scan with about 15 mCi of [11C]MC1 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day. In a second visit, participants had a baseline whole body PET/CT scan after receiving about 15 mCi of [11C]ER176 followed by a second whole body PET/CT scan with about 15 mCi of [11C]ER176 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day.
干预措施: 11C-MC1 (Drug)
Phase 2: Whole body PET/CT scans in healthy participants
Healthy participants had a baseline whole body PET/CT scan after receiving about 15 mCi of [11C]MC1 followed by a second whole body PET/CT scan with about 15 mCi of [11C]MC1 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day. In a second visit, participants had a baseline whole body PET/CT scan after receiving about 15 mCi of [11C]ER176 followed by a second whole body PET/CT scan with about 15 mCi of [11C]ER176 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day.
干预措施: Celecoxib (Drug)
Phase 2: Whole body PET/CT scans in healthy participants
Healthy participants had a baseline whole body PET/CT scan after receiving about 15 mCi of [11C]MC1 followed by a second whole body PET/CT scan with about 15 mCi of [11C]MC1 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day. In a second visit, participants had a baseline whole body PET/CT scan after receiving about 15 mCi of [11C]ER176 followed by a second whole body PET/CT scan with about 15 mCi of [11C]ER176 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day.
干预措施: [11C]ER176 (Drug)
Phase 2: Whole body PET/CT scans in healthy participants
Healthy participants had a baseline whole body PET/CT scan after receiving about 15 mCi of [11C]MC1 followed by a second whole body PET/CT scan with about 15 mCi of [11C]MC1 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day. In a second visit, participants had a baseline whole body PET/CT scan after receiving about 15 mCi of [11C]ER176 followed by a second whole body PET/CT scan with about 15 mCi of [11C]ER176 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day.
干预措施: Positron Emission Tomography (PET)/computed tomography (CT) Scan (Diagnostic Test)
Phase 3: Brain PET/CT scans in healthy participants
Healthy participants had a baseline brain PET/CT scan after receiving about 20 mCi [11C]MC1 followed by a second brain PET/CT scan with 20 mCi [11C]MC1 intravenously after blockade with single dose of celecoxib 600 mg orally on same day. Participants had arterial blood sampling with each brain scan.
干预措施: 11C-MC1 (Drug)
Phase 3: Brain PET/CT scans in healthy participants
Healthy participants had a baseline brain PET/CT scan after receiving about 20 mCi [11C]MC1 followed by a second brain PET/CT scan with 20 mCi [11C]MC1 intravenously after blockade with single dose of celecoxib 600 mg orally on same day. Participants had arterial blood sampling with each brain scan.
干预措施: Celecoxib (Drug)
Phase 3: Brain PET/CT scans in healthy participants
Healthy participants had a baseline brain PET/CT scan after receiving about 20 mCi [11C]MC1 followed by a second brain PET/CT scan with 20 mCi [11C]MC1 intravenously after blockade with single dose of celecoxib 600 mg orally on same day. Participants had arterial blood sampling with each brain scan.
干预措施: Positron Emission Tomography (PET)/computed tomography (CT) Scan (Diagnostic Test)
结局指标
主要结局
Uptake of [11C]MC1 by Organs
时间窗: Up to 120 minutes during each scan
Participant received whole body PET/CT scan and radioligand uptake of \[11C\]MC1 in selected body regions of interest was quantified as a Standardized Uptake Value (SUV) using the Siemens Biograph Micro-Computed Tomography (mCT) with an injected dose of 9 mCi. Organ dosimetry was measured as dose per organ in Roentgen Equivalent Man (rem), which is absorbed dose times an organ-specific quality factor.
Uptake of [11C]MC1 by Organs - Gender Specific Organs
时间窗: Up to 120 minutes during each scan
Participant received whole body PET/CT scan and radioligand uptake of \[11C\]MC1 in selected body regions of interest was quantified as a Standardized Uptake Value (SUV) using the Siemens Biograph Micro-Computed Tomography (mCT) with an injected dose of 9 mCi. Organ dosimetry was measured as dose per organ in Roentgen Equivalent Man (rem), which is absorbed dose times an organ-specific quality factor.
Phase 2: [11C]MC1 Binding in Inflamed Body Parts - HANDS
时间窗: Up to 120 minutes during each scan
The uptake of \[11C\]MC1 before (baseline) and after blockade by single dose of celecoxib 400mg orally in inflamed regions of the body in patients. The radioligand uptake of \[11C\]MC1 during whole body PET/CT scans in selected regions of interest was quantified as a Standardized Uptake Value (SUV), which normalizes for injected activity and body weight, using Bruker's PMOD quantification software.
Phase 2: [11C]MC1 Binding in Non-inflamed Body Parts - HANDS
时间窗: Up to 120 minutes during each scan
The uptake of \[11C\]MC1 before (baseline) and after blockade by a single dose of celecoxib 400mg orally in non-inflamed regions of the body in healthy participants. The radioligand uptake of \[11C\]MC1 during whole body PET/CT scans in selected regions of interest was quantified as a Standardized Uptake Value (SUV), which normalizes for injected activity and body weight, using Bruker's PMOD quantification software.
Phase 2: [11C]MC1 Binding in Inflamed Body Parts - KNEES
时间窗: Up to 120 minutes during each scan
The uptake of \[11C\]MC1 before (baseline) and after blockade by a single dose of celecoxib 400mg orally in inflamed regions of the body in patients. The radioligand uptake of \[11C\]MC1 during whole body PET/CT scans in selected regions of interest was quantified as a Standardized Uptake Value (SUV), which normalizes for injected activity and body weight, using Bruker's PMOD quantification software.
Phase 2: [11C]MC1 Binding Between Non-inflamed Body - KNEES
时间窗: Up to 120 minutes during each scan
The uptake of \[11C\]MC1 before (baseline) and after blockade by a single dose of celecoxib 400mg orally in non-inflamed regions of the body in healthy participants. The radioligand uptake of \[11C\]MC1 during whole body PET/CT scans in selected regions of interest was quantified as a Standardized Uptake Value (SUV), which normalizes for injected activity and body weight, using Bruker's PMOD quantification software.
Whole Brain Volume of Distribution (VT)/ Free-fraction (fP) of [11C]MC1
时间窗: Up to 120 minutes during each scan
The volume of distribution (VT) of \[11C\]MC1 measured as the brain-to-plasma ratio using the 2-tissue compartmental modeling divided by free-fraction in the plasma of parent radioligand (fP) at baseline and two hours after blockade with single dose of 600 mg celecoxib orally.
次要结局
未报告次要终点