SNPMiner Trials (Home Page)
Report for Mutation A147T
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 3 clinical trials
Clinical Trials
1 PET Evaluation of Brain Peripheral Benzodiazepine Receptors Using [(11)C]PBR28 in Patients With Multiple Sclerosis (MS)
This study will use positron emission tomography (PET) to measure a brain protein called peripheral benzodiazepine receptor (PBR) in patients with multiple sclerosis. PBR is created during the inflammation process, and brain inflammation is a key feature of multiple sclerosis (MS). PBR usually affects one type of brain cell, but it can also cause damage to surrounding areas of the brain in patients with MS. PET studies of PBRs and brain inflammation may help elucidate the role of these brain cells in patients with MS. Healthy normal volunteers and patients with MS between 18 and 70 years of age may be eligible for this study. Patients with MS must have had onset of disease between 18 and 40 years of age. Patients with MS undergo the following procedures: Visit 1: Medical history, physical examination, blood tests and magnetic resonance imaging (MRI). Visit 2: Blood tests and PET scan. Visits 3 and 4: MRI and physical examination. Visit 5: PET scan and blood tests. Visit 6: MRI and physical examination. Healthy volunteers undergo the following: Visit 1: Medical history, physical examination, blood tests. Visits 2 and 3: PET and blood tests. Magnetic Resonance Imaging MRI uses a magnetic field and radio waves to produce images of body tissues and organs. For this procedure, the subject lies on a table that can slide in and out of the scanner (a metal cylinder), wearing earplugs to muffle loud knocking noises that occur during the scanning process. The procedure lasts about 90 minutes; the patient is asked to lie still for up to 25 minutes at a time. The subject can communicate with the MRI staff at all times during the scan. During part of the scan a contrast agent is administered through a catheter (plastic tube) placed in an arm vein to enhance the images. Positron Emission Tomography (PET) The PET scan gives information on brain and body chemistry and function. The subject lies on a bed that slides in and out of the doughnut-shaped scanner. A catheter is placed in a vein in the arm and another is placed in an artery in the wrist or elbow area. The catheter in the arm is used for injecting a radioactive material that the scanner detects, and the other is used to collect blood samples. A custom-molded plastic mask is used to support the head and prevent it from moving during the procedure. The subject may be asked to perform various tasks during the PET scan or to lie quietly. The scan lasts about 2.5 hours.
NCT00432900 Multiple Sclerosis Radiation: [(11)C]PBR28 MeSH:Multiple Sclerosis Sclerosis
- Homozyous for the low- affinity binding form of TSPO by TSPO genotype analysis ( Ala147Thr polymorphism in rs6971 SNP in exon 4 of the TSPO gene). --- Ala147Thr ---
HEALTHY VOLUNTEERS - EXCLUSION CRITERIA: Homozyous for the low- affinity binding form of TSPO by TSPO genotype analysis ( Ala147Thr polymorphism in rs6971 SNP in exon 4 of the TSPO gene). --- Ala147Thr ---
Primary Outcomes
Measure: Correspondence between increased PBR expression measured by [11C]PBR28 PET and gadolinium-enhancing lesions on MRI. Time: At time of dosingMeasure: Correspondence between increased PBR expression and previously and/or persistently gadolinium-enhancing lesions on MRI. Time: At time of dosing
Secondary Outcomes
Measure: Correspondence between PBR expression and other MRI defined pathology including T2-weighted hyperintense and T1-weighted hypointense lesions. Time: Follow-up (~Month 4)Measure: Correspondence between PBR expression and normal appearing white and gray matter on MRI. Time: Follow-up (~Month 4)
2 Positron Emission Tomography Measurement of Neuroinflammation in Focal Epilepsy
Background:
- The brain is protected by a barrier that keeps toxins in the blood from reaching the
brain. However, this barrier can also keep useful medications from reaching the brain.
P-glycoprotein (P-gp) is a brain protein that is part of the blood-brain barrier. The
level of P-gp is higher in people with epilepsy than in people without epilepsy. These
different levels of P-gp may explain why some people have seizures that do not respond
well to medications. Researchers want to see if P-gp can affect the response to epilepsy
medications.
- Epilepsy may also be associated with brain inflammation. Researchers also want to look
at the part of the brain affected by epilepsy to see if inflammation is present.
Objectives:
- To see if P-gp can affect the response to epilepsy medications.
- To see if inflammation is present in the part of the brain affected by epilepsy.
Eligibility:
-
NCT01663545 Epilepsies, Partial MeSH:Epilepsy Epilepsies, Partial
HPO:Focal aware seizure Focal emotional seizure with laughing Focal sensory seizure Seizure
This polymorphism is due to the non-conservative amino-acid substitution at position 147 from alanine to threonine (Ala147Thr) in the fifth transmembrane domain of the TSPO protein. --- Ala147Thr ---
Primary Outcomes
Measure: Amount of differential [11C]dLop and [11C]PBR28 uptake between the epileptic focus and the homologous contralateral region Time: study completionSecondary Outcomes
Measure: Secondary Outcome Measure: A secondary goal is to determine if inhibiting P-gp with tariquidar results in increased concentrations of anti-epileptic medications into the CSF, as a surrogate marker for increased penetration of these medication... Time: study completion3 An Adaptive Design Open Label Pilot Study in Rheumatoid Arthritis Patients to Assess Inflammation Using Molecular Imaging Techniques
This is an adaptive Positron Emission Tomography/ Computed Tomography (PET/CT) and Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) open-label study design for the investigation of inflammation in adult rheumatoid arthritis (RA) patients, not involving therapeutic intervention. Each study participant will undergo two half body PET/CT scans from the pelvis to the bottom of the feet (including hands and wrists) with an additional bed position centred on the shoulders. One scan will be conducted with 18F-FDG and the other with 18F-GE-180. The first PET/CT scan (PET1) will be performed 4 weeks (28 +/- 2 days) after the first screening visit, whereas the second PET/CT scan (PET2) will be carried out within 2 weeks (7 +/- 7 days) after PET1. The order of PET/CT scans for each subject will be based on a computer generated randomisation schedule after the screening visit. A sub-group of study participants will be invited to undergo an additional dynamic 18F-GE-180 PET scan of a selected joint (knee or wrist) prior to their 18F-GE-180 PET/CT half body scan. The primary objective of the study is to quantify inflammation in joints of RA patients by determining 18F-FDG and 18F-GE-180 uptake using PET, and DCE-MRI parameters.
NCT02350426 Arthritis, Rheumatoid Other: Gadobutrol Other: 18F-FDG Other: 18F-GE-180 MeSH:Arthritis Arthritis, Rheumatoid Inflammation
HPO:Arthritis Polyarticular arthritis Rheumatoid arthritis
- Contraindication to MRI scanning (as assessed by local MRI safety questionnaire) which includes, but is not limited to, intracranial aneurysm clips or other metallic objects, history of intra-orbital metal fragments that have not been removed by a medical doctor MD), presence of a cardiac pacemaker, non-magnetic resonance (MR) compatible heart valves or other electronic device or ferromagnetic metal foreign bodies, inner ear implants or history of cancer in first degree relatives diagnosed before age of 55. - Presence of Ala147Thr polymorphism in translocator protein (TSPO) (which confers low affinity binding of 18F-GE-180) following confirmation by genotyping assay. --- Ala147Thr ---
Primary Outcomes
Description: Half body and shoulder images from 18F-FDG and 18F-GE-180 will be visually inspected by two nuclear medicine physicians with respect to the clarity and ease of identifying abnormal high uptake in joints suspected to have inflammation. A subjective scale of abnormality will be applied to each image as follows: 3 = excellent quality; 2 = intermediate quality; 1 = poor quality but still interpretable; 0 = poor quality, not interpretable.
Measure: Evaluator's assessment of image quality and potential to define abnormality Time: Week 8Description: SUV will be derived from PET static imaging for 18F-FDG and 18F-GE-180 in selected joints. Using normalisation by weight and body surface area, SUVmax, SUVpeak and SUVmean (average of voxel values above a 75% iso-contour of SUVmax) will be calculated within the joint volume.
Measure: Standardised Uptake Value (SUV) of 18F-FDG and 18F-GE-180 Time: Week 8Description: TR will be derived from PET static imaging for 18F-FDG and 18F-GE-180 in selected joints. TR will be determined using the mean image value within each joint volume, and either the blood concentration decay-corrected to the start of the PET acquisition or the mean image value within non-inflamed muscle as reference.
Measure: Tissue-to-reference Ratio (TR) of 18F-FDG and 18F-GE-180 Time: Week 8Description: TIV will be derived from PET static imaging for 18F-FDG and 18F-GE-180 in selected joints.
Measure: Total Inflammatory Volume (TIV) of 18F-FDG and 18F-GE-180 Time: Week 8Description: Ktrans will be derived from DCE-MRI in selected joints
Measure: Exchange Rate (Ktrans) Time: Week 8Description: Ve will be derived from DCE-MRI in selected joints
Measure: Interstitial Volume (Ve) Time: Week 8Description: IRE will be derived from DCE-MRI in selected joints
Measure: Initial Rate of Enhancement (IRE) Time: Week 8Description: ME will be derived from DCE-MRI in selected joints
Measure: Maximal Signal Intensity Enhancement (ME) Time: Week 8Secondary Outcomes
Description: 18F-FDG and 18F-GE-180 static images will be evaluated by experienced observers with respect to the ease of identifying high uptake in joints suspected to have inflammation. Images will be assessed on the basis of a 4-point visual scale of abnormality/discernibility (0=poor quality - 4=excellent quality) and the number of abnormal joints will be counted.
Measure: Visual assessment of static 18F-FDG and 18F-GE-180 images using a 4-point visual analysis scale and abnormal joint counts Time: Week 8Description: The correlation between PET static imaging parameters (SUV, TR and TIV) of 18F-FDG and 18F-GE-180 will be determined
Measure: PET static imaging parameters (SUV, TR and TIV) of 18F-FDG and 18F-GE-180 in selected joints Time: Week 8Description: In order to verify static imaging parameters for scans, the pharmacokinetic profile of 18F-GE-180 will be determined, using dynamic PET scanning, blood sampling and HPLC analysis in a sub-cohort of RA study patients. 18F-GE-180 radio-PK parameters will be correlated with 18F-GE-180 static imaging metrics (SUV, TR and TIV)
Measure: 18F-GE-180 radio-PK modelling indices (total distribution volume; VT) and 18F-GE-180 static imaging metrics (SUV, TR and TIV) Time: Week 8Description: Number of AEs and SAEs as a measure of safety and tolerability of 18F-GE-180 and 18F-FDG
Measure: Adverse events (AEs) and serious adverse events (SAEs) assessment Time: Week 8