SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02350426

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

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
MeSH: Arthritis Arthritis, Rheumatoid Inflammation
HPO: Arthritis Polyarticular arthritis Rheumatoid arthritis

3 Interventions

Name: Gadobutrol

Description: Gadobutrol is a solution for intravenous (IV) injection in prefilled syringe/cartridge with a unit dose strength of 1.0 millimole (mmol)/mL solution, and will be administered at up to 0.1mmol/kg.

Type: Other

Arm 2 Arm 1

Name: 18F-FDG

Description: 18F-FDG is a solution for IV injection in multidose vial, maximum 10 mL with unit dose strength of 160 megabecquerel (MBq) at maximum.

Type: Other

Arm 2 Arm 1

Name: 18F-GE-180

Description: 18F-GE-180 solution for IV injection in 10mL glass vial. Patients will receive a maximum activity of 195 MBq in a maximum volume of 10 mL (bolus) of 18F-GE-180, containing not more than 2 microgram (mcg)/mL 18F-GE-180 (20 mcg for a 10 mL dose).

Type: Other

Arm 2 Arm 1


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 8

Description: 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 8

Description: 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 8

Description: 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 8

Description: Ktrans will be derived from DCE-MRI in selected joints

Measure: Exchange Rate (Ktrans)

Time: Week 8

Description: Ve will be derived from DCE-MRI in selected joints

Measure: Interstitial Volume (Ve)

Time: Week 8

Description: IRE will be derived from DCE-MRI in selected joints

Measure: Initial Rate of Enhancement (IRE)

Time: Week 8

Description: ME will be derived from DCE-MRI in selected joints

Measure: Maximal Signal Intensity Enhancement (ME)

Time: Week 8

Secondary 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 8

Description: 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 8

Description: 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 8

Description: 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

Purpose: Basic Science

Allocation: Randomized

Crossover Assignment


There is one SNP

SNPs


1 A147T

- 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 ---



HPO Nodes


HPO:
Arthritis
Genes 172
COL2A1 HJV COL3A1 IL10 RNASEH2B GDF5 IL12A RAG1 COL5A1 HGD IL12B RAG2 COL5A2 TREX1 DNAJB11 NLRP12 HNF1B COL9A1 TCF3 COL9A2 COL9A3 COL11A1 COL11A2 ATP7B RNF168 ZMPSTE24 UFSP2 ANK1 WAS COMP COMT WIPF1 MLX HLA-B RNASEH2A ERAP1 LEMD3 SLC26A2 HLA-DRB1 GJB6 MATN3 SPTA1 ACP5 SPTB SH3KBP1 TRPS1 PSMB4 BLNK PSMB9 GBA CASP10 PTPN22 IRF5 SAMHD1 EXT1 GCH1 EXT2 OCRL AIP CAV1 LBR PSTPIP1 APOE PFKM GPR101 RREB1 CFI FAS FASLG HNF4A ADAR ADA2 TF ANKRD55 ANKH F8 SLC40A1 KLRC4 F9 JMJD1C MEFV NLRC4 NLRP3 STAT3 STAT4 SLC4A1 HIRA KIF7 TFR2 NOD2 GHR PHEX TGFB3 CCN6 IFIH1 PTPN2 RASGRP1 GJB2 CD247 FBN1 IL36RN GLA SLC12A3 SEC24C LMNA CLCN7 CLCNKB HOXD10 AEBP1 ARVCF DCLRE1C CANT1 LACC1 MYH14 LMX1B MTHFD1 ASAH1 IL12A-AS1 AGA PIK3R1 ACAN HPGD SLCO2A1 HPRT1 IGHM SCARB2 BTK RNASEH2C UFD1 MIF TLR4 LRRC8A UMOD PRKCD CD79A TRPV4 CD79B CCR1 UBAC2 C4A CCN2 CCR6 FGFR3 IGLL1 GNAS LRBA TNFRSF1A MMP13 MUC1 IL2RA SEC61A1 PRG4 IL2RB EPCAM G6PC TNXB SLC37A4 DNASE1L3 ABCG5 IL6 ABCG8 IL23R TBX1 EPB42 MVK ZNF687 SMAD3 KIF22 GP1BB COL1A1 PRPS1 TRAPPC2
Polyarticular arthritis
Genes 13
IL2RA IL2RB PTPN2 ANKRD55 NLRP1 PTPN22 ENPP1 MEFV CD247 STAT4 TNFAIP3 DMP1 NOD2
Rheumatoid arthritis
Genes 14
DCLRE1C IL2RA IL2RB LACC1 PTPN2 ANKRD55 PTPN22 IL6 GCH1 HLA-DRB1 ACP5 CD247 STAT4 MIF