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Report for Clinical Trial NCT02350426

Developed by Shray Alag, 2020.
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 1 Arm 2

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 1 Arm 2

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 1 Arm 2


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 263
COL5A2 HPGD COL1A1 CANT1 HJV TRPV4 CCR1 HNF1B PTPN2 LACC1 BTK TFR2 HOXD10 CLCN7 COL9A2 PTPN22 MMP2 NLRP3 STAT4 GHR RNF168 TREX1 COL9A3 PADI4 SLC40A1 WIPF1 COL2A1 MMP14 RASGRP1 PRKCD SEC61A1 SLC37A4 COL2A1 HNF1B TBX1 PTPN22 STAT4 MEFV AEBP1 COL2A1 IL2RB HLA-DRB1 HGD PSTPIP1 ANKRD55 FBN1 GBA HPGD CCN6 ANKRD55 FGFR3 NOD2 ACAN COMP HPRT1 AGA IRF5 NLRC4 MUC1 IL12B GNAS HPGD MATN3 CASP10 ASAH1 COMP MYH14 HIRA SLCO2A1 SLC22A4 HLA-B FRZB CD244 PRG4 COL11A2 LMX1B TNFRSF1A ACAN TGFB3 STAT4 COL11A1 IL10 MEFV LRP6 RAG2 IFIH1 TRAPPC2 LBR IL10 COL5A1 IGHM LEMD3 HLA-DRB1 DNASE1 COMP SH3KBP1 NFKBIL1 IL12A-AS1 IL12A ARVCF COL2A1 CLCN7 IL23R KIF7 DNASE1L3 SEC24C IL6 FCGR2A COL9A3 SLC37A4 AIP SPTB HPRT1 GDF5 COL2A1 JMJD1C TCF3 IL2RB COMP HLA-B TRAPPC2 COL5A1 HNF4A F9 COMT UFD1 SMAD3 STAT3 HPRT1 HGD SPTA1 GJB6 ATP7B COL9A1 F8 BLNK PTPN22 APOE UMOD TREX1 MMP13 ZNF687 NLRP3 GJB2 PSMB9 PTPN22 TF CD79B COL2A1 MMP13 LMNA UFSP2 ERAP1 LRBA COPA CCR6 COL9A2 ABCG8 TRPS1 CD247 MIF C1R GP1BB PFKM LRRC8A FAS PHEX UMOD ANKH G6PC FCGR2B COL2A1 CCN6 IGLL1 CAV1 PSTPIP1 NLRP12 KIF22 ANKH SPP1 ATP7B CTLA4 CD79A SLC4A1 RNASEH2B EPCAM FAS NLRP3 CCN2 WAS COL1A1 PSMB4 UFSP2 TLR4 STAT4 MVK ACP5 MATN3 HPRT1 SLC12A3 BTK MTHFD1 ADA2 RAG1 PIK3R1 SCARB2 OCRL ADAR HLA-DRB1 RREB1 COL11A2 RNASEH2C PTPN22 GPR101 IL36RN CIITA C1QA SLC26A2 NLRP3 PHEX RNASEH2A KLRC4 COL2A1 ZMPSTE24 CD247 CFI UBAC2 BTK HLA-B DNAJB11 GCH1 FAS C4A COL11A2 EPB42 PRPS1 IRAK1 EXT2 MEFV MEFV GLA ACAN FASLG MVK MATN3 CLCNKB IL2RA EXT1 ASPN COL3A1 IL2RA TBX1 COL9A1 NOD2 HLA-C COL2A1 ANK1 TRPV4 SAMHD1 PTPN2 SMAD3 MLX DCLRE1C
Polyarticular arthritis
Genes 13
ANKRD55 IL2RB ENPP1 NOD2 STAT4 TNFAIP3 IL2RA NLRP1 DMP1 PTPN22 CD247 PTPN2 MEFV
Rheumatoid arthritis
Genes 28
NFKBIL1 ACP5 PTPN2 LACC1 IL2RB SLC22A4 IL6 HLA-DRB1 PTPN22 CD244 PTPN22 ANKRD55 STAT4 ANKRD55 IL2RB PADI4 PTPN22 IL2RA CIITA STAT4 IL2RA IL10 CD247 PTPN2 CD247 GCH1 MIF DCLRE1C