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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
Group Labels: 2

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
Group Labels: 2

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
Group Labels: 2

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:
HP:0001369: Arthritis
Genes 263
MEFV COL2A1 NLRP3 COL1A1 COL5A1 HLA-DRB1 STAT4 MLX GPR101 IL2RA CLCN7 IL10 KLRC4 SCARB2 NOD2 MUC1 PTPN22 FGFR3 ABCG8 IL12A COPA FASLG SLC12A3 LRRC8A MATN3 COMP OCRL LACC1 IRAK1 RNASEH2B SLC37A4 ZMPSTE24 SPTB MMP13 IL12A-AS1 AGA PSTPIP1 ERAP1 SH3KBP1 TRPV4 CD79B LBR SMAD3 SPTA1 DNASE1L3 HLA-C UFSP2 TGFB3 TBX1 COL2A1 ANKH EPCAM COL2A1 NLRP3 ATP7B PTPN22 IFIH1 CLCNKB MTHFD1 HIRA SLC40A1 MVK TRPS1 GCH1 ANK1 HOXD10 UFD1 COL2A1 CD79A COL11A2 RNASEH2A HPRT1 LRBA FRZB SLC22A4 HGD BLNK PSMB9 GDF5 TCF3 KIF7 GHR HGD CCN6 FAS HLA-B LMNA ACAN CIITA JMJD1C ACAN TRAPPC2 PRG4 ADAR FCGR2A UMOD GNAS KIF22 HPRT1 AEBP1 CD244 CFI MEFV C4A COL9A2 CAV1 IL2RA UBAC2 PTPN22 FCGR2B NLRP3 RAG1 CD247 MATN3 IL23R DCLRE1C LRP6 COL9A3 LMX1B COL11A2 HLA-B SEC24C CLCN7 ADA2 BTK C1R GBA TF MMP13 ANKH PHEX COL2A1 SEC61A1 COL9A2 HLA-DRB1 SLC4A1 SLCO2A1 UFSP2 HNF1B F9 PIK3R1 GLA MMP2 COL3A1 COMP CTLA4 TLR4 COL9A3 COL1A1 ASAH1 STAT4 COL9A1 HPRT1 IL10 GJB6 CD247 COL5A2 CANT1 IL2RB BTK LEMD3 RASGRP1 CASP10 AIP ASPN COMT ACP5 FBN1 SLC26A2 MVK COMP STAT4 ARVCF WAS EPB42 NLRP12 UMOD CCN6 ZNF687 PFKM PTPN2 SLC37A4 PTPN22 TNFRSF1A HNF4A RNASEH2C TFR2 COL5A1 TREX1 COMP PSMB4 DNASE1 DNAJB11 EXT1 NOD2 BTK APOE NLRC4 TRPV4 TBX1 PRKCD COL2A1 F8 TREX1 COL2A1 MYH14 PRPS1 SMAD3 IL36RN HPGD ANKRD55 C1QA SAMHD1 COL11A2 MATN3 EXT2 PHEX RREB1 CCR6 RAG2 ANKRD55 CCN2 HJV MEFV IL12B IRF5 FAS CCR1 COL11A1 STAT4 NFKBIL1 PSTPIP1 COL9A1 TRAPPC2 ACAN G6PC HLA-DRB1 COL2A1 SPP1 IL2RB MMP14 HPGD PADI4 GP1BB RNF168 PTPN22 COL2A1 WIPF1 NLRP3 HPRT1 PTPN2 IGHM FAS GJB2 HPGD STAT3 IGLL1 MEFV IL6 ATP7B HNF1B HLA-B MIF
Protein Mutations 4
A147T N363S R620W V600E