SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02086240

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Reproducibility of the 11C-PBR28 PET Signal

The Translocator Protein (TSPO) is a protein which reaches very high levels when there is inflammation in the brain. Recently, radioligands have been developed which attach to the TSPO (a radioligand is a drug which has been tagged with radioactivity). Using positron emission tomography (PET) imaging, the radioligand can be detected following injection into a patient. However, it is difficult to accurately measure the amount of TSPO using PET at the moment. This is because the brain does not have a "reference region" for TSPO (ie an area in the brain with no TSPO at all). "Reference regions" are very useful to help work out how much of a PET signal represents "specific binding" (of the radioligand to the target of interest), and how much represents "non specific binding" (of the radioligand to many other structures which are not of interest). In the absence of a reference region, non specific binding can be estimated by giving a drug which binds to the TSPO. The drug prevents the radioligand binding the TSPO and (in a manner of speaking) "creates" a temporary reference region so non specific binding can be measured. To do this, we will use XBD173 (Emapunil is an anxiolytic drug which acts as a selective agonist at the peripheral benzodiazepine receptor) to bind TSPO and block binding of the PET ligand ([11C]PBR28), a TSPO ligand from the phenoxyarlyacetamide class. Most TSPO PET studies (and in one of our previous studies approved by West London REC) quantify the signal using a ratio of specific binding in the brain to radioactivity in the blood. This requires arterial line insertion which is burdensome for subjects, and increases variability. In this study we aim to determine the ratio of specific binding in the brain to nonspecific binding in the brain by using the temporary reference region. For more accuracy the participants will repeat the scanning procedure so determine test-retest variability of the amount of TSPO.

NCT02086240 Neurodegenerative Disorders
MeSH: Neurodegenerative Diseases
HPO: Neurodegeneration

1 Interventions

Name: XBD173

Description: XBD173 (Emapunil is an anxiolytic drug which acts as a selective agonist at the peripheral benzodiazepine receptor), a drug which binds the TSPO with high affinity.

Type: Drug

XBD173


Primary Outcomes

Description: Participants will be screened to determine TSPO genotype at the rs6971 polymorphism from a venous blood sample.

Measure: TSPO Binding Status

Time: Baseline/Screening visit

Other Outcomes

Description: Determination of test re-test variability of both BPND and VT for 11CPBR28 in healthy volunteers and MS patients. Subjects will receive a baseline 11C-PBR28 scan, and then a repeat scan following an oral dose of 90mg XBD173 (Emapunil). Both VT and BPND will be determined. Subjects will then return approximately 10 days later for a repeat of these procedures.

Measure: To determine test re-test variability of both BPND and VT for [11C]PBR28 in healthy volunteers and MS patients.

Time: 1st and 2nd Study Visit (approximately 10 days after the 1st study visit)

Purpose: Basic Science

Single Group Assignment


There is one SNP

SNPs


1 rs6971

Participants will be screened to determine TSPO genotype at the rs6971 polymorphism from a venous blood sample.. To determine test re-test variability of both BPND and VT for [11C]PBR28 in healthy volunteers and MS patients.. Determination of test re-test variability of both BPND and VT for 11CPBR28 in healthy volunteers and MS patients.



HPO Nodes


HPO:
Neurodegeneration
Genes 72
VAPB CCNF RNASEH2B IFIH1 NEFH PPARGC1A TARDBP TREX1 NEK1 WDR45 ERBB4 CHCHD10 OPTN GALC PANK2 ZBTB20 UBQLN2 ANG AARS2 RNASEH2A ATXN2 FIG4 FOLR1 GLE1 PDE8B SQSTM1 GUSB UBTF FA2H UCHL1 C19ORF12 MATR3 TBK1 ANXA11 RNASEH2C NAXD ATXN3 TREM2 PON1 PON2 PON3 GM2A DAO NBN PLA2G6 FTL SAMHD1 MFSD8 TAF15 ABCD1 FUS COASY TANGO2 IDS C9ORF72 PFN1 IDUA TXN2 ADAR DCTN1 LYST HNRNPA1 UNC13A NARS2 CFAP410 TTC19 PCNA SOD1 VCP CHMP2B EPHA4 PRPH