Ignite Creation Date:
2024-10-25 @ 8:02 PM
Last Modification Date:
2024-10-26 @ 3:42 PM
Study NCT ID:
NCT06633484
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
None
First Post:
2024-07-30
Brief Title:
BIOMIGA Results from Magnetic Resonance Imaging
Sponsor:
None
Organization:
None
Study Overview
Official Title:
BIOmarkers of MIGraine a Proof of Concept Study on the Stratification of Responders to CGRP Monoclonal Antibodies - Results from Magnetic Resonance Imaging
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The projects comprising in the multicenter BIOMIGA project have been preregistered earlier with ID NTC04503083 at clinicaltrialsgov Here the imaging subproject within the overall BIOMIGA aims is specified The hypotheses for this subproject of the magnetic resonance imaging part is based on hypotheses generating analyses of the data from one site Hamburg Germany of this three-center study At all three sites healthy controls and migraine patients underwent identical protocols with 3 types of magnetic resonance imaging including structural scans MPRAGE resting-state functional magnetic resonance imaging rs-fMRI as well as arterial spin labeling ASL with matched protocols across sites Data was acquired before CGRP-antibody administration day 1 and 12 weeks afterwards day 2 We analyzed the data from one site Hamburg Germany as hypotheses generating published these data as a poster and aim to validate our results with the not-yet analyzed data from the two other sites Pavia Italy and Barcelona Spain
Detailed Description:
The Hamburg data was processed as stated below and will be used as independent data set for hypotheses generation The data of the two other sites Italy and Spain will be processed identically to the Hamburg data set
rs-FMRI
Preprocessing of the resting-state functional MR data followed the SPM12 pipeline httpswwwfilionuclacukspmsoftwarespm12 using slice time correction realignment coregistration to the structural image normalization into MNI space and smoothing with an 8mm3 Gausian kernel Data was further analyzed using the CONN-toolbox httpswebconn-toolboxorg where a 0003-008 Hz temporal filter and denoising with linear regression of confounding effects white matter CSF movement and linear detrending We choose
Local Homogeneity LCOR
Global Correlations GCOR
Seed-Based Correlations SBC Seed to voxel and ROI to ROI with an additional mask of the hypothalamus
Independent Component Analyses group-ICA
Amplitude of Low-Frequency Fluctuations ALFF
Statistical comparisons calculated are defined as primary and secondary outcomes below and include i prediction of treatment outcome reduction in headache days from T0 further PR ii alterations between T0 and T1 iii differences between healthy controls and migraine patients at T0 further HvsPAT and iv differences between responders and non-responder at T0 and T1
In the hypothesis generating Hamburg data significant results at a threshold of cluster-wise FDR-corrected p005 with an entry threshold of voxel-wise uncorrected p0001 when corrected for age and sex in were found
LCOR PR Two clusters in left lateral occipital cortex and right temporal fusiform cortex HvsPAT bilateral thalamus left frontal operculum
SBC Seed to Voxel PR Hypothalamus 2 clusters Sensori Motor Lateral R 1 cluster Visula Lateral L 1 cluster Visual Lateral R 3 cluster HvsPAT Sensori Motor Lateral L 5 cluster Sensori Motor Lateral R 1 cluster Sensori Motor Superior 3 cluster Visual Medial 3 cluster Visual Occipital 1 cluster Visual Lateral L 4 cluster Visual Lateral R 1 cluster
ICA ICA 5 2 cluster ICA 16 2 cluster ICA 28 1 cluster ICA 34 2 cluster HvsPAT ICA 4 3cluster ICA 6 4 cluster ICA 14 4 cluster ICA 18 2 cluster ICA 27 3 cluster ICA 29 14 cluster ICA 33 3 cluster ICA 36 7 cluster ICA 38 6 cluster
There were no significant results for SBC ROI to ROI GCOR and ALFF
There were no significant results for the chosen threshold for the comparisons between responders and non-responder at T0 and T1 Preliminary results for local and global connectivity were recently presented at a scientific conference
To reproduce the significant results from the Hamburg data there is choosen a small volume-corrected threshold of p005 For non-significant result the statistical threshold for the data of the two other sites will be set to voxel-wise FWE-corrected p005
MPRAGE Raw T1-images aka MPRAGE were processed using the CAT12-toolbox httpsneuro-jenagithubiocat12-help which extents SPM12 httpswwwfilionuclacukspmsoftwarespm12 For controls and migraine patients with data from only the first day images segmented into compartments of gray and white matter and normalized For patients with data from 2 days data was longitudinally segmented Images of gray and white matter were smoothed with an isotropic Gaussian kernel of 6 mm3 T-test and F-tests implemented in the SPM12 toolbox were used to estimate significant differences at a threshold of cluster-wise-correct p005 The individual total intracranial volume TIV which is also estimated by the CAT12-toolbox was used as covariate to control for different brain sizes Age and gender were used as further covariates when indicated All results were masked by gray or white matter masks stemming from a segmentation of the average normalized T1s of the participants The statistical threshold for the hypotheses generating data set from Hamburg was set to cluster-wise FDR-corrected p005 with an entry threshold of voxel-wise uncorrected p0001 As no significant results were achieved the statistical threshold for the data of the two other sites will be set to voxel-wise FWE-corrected p005
ASL ASL was not yet analyzed for any of the sites For the statistics we will use Cerebral Perfusion Images stemming from the toolbox ASLtbx httpswwwcfnupenneduzewangASLtbx_manualpdf Nevertheless as different imaging protocols were available in Spain and Italy a comparison of the equality has to be proofen first Therefore we acquired both protocols in the Hamburg data As we do not expect any differences here the statistical threshold will be set to voxel-wise FWE-corrected p005
Power calculation based on Hamburg MR data Power analysis of the primary outcome prediction of headache reduction with resting-state functional connectivity measures from fMRI of day 1 for which rs-fMRI data of 54 migraine patients from the hypothesis generating site Hamburg were analyzed using the CONN-toolbox revealed that 37 migraine patients are necessary to reproduce the result of significant comodulation in local correlation when corrected for age and gender 80 Power FWE-corrected p005 calculated with PowerMap Initial quality checks of the data from the other two sites reveal enough available data for reproduction
rs-FMRI
Preprocessing of the resting-state functional MR data followed the SPM12 pipeline httpswwwfilionuclacukspmsoftwarespm12 using slice time correction realignment coregistration to the structural image normalization into MNI space and smoothing with an 8mm3 Gausian kernel Data was further analyzed using the CONN-toolbox httpswebconn-toolboxorg where a 0003-008 Hz temporal filter and denoising with linear regression of confounding effects white matter CSF movement and linear detrending We choose
Local Homogeneity LCOR
Global Correlations GCOR
Seed-Based Correlations SBC Seed to voxel and ROI to ROI with an additional mask of the hypothalamus
Independent Component Analyses group-ICA
Amplitude of Low-Frequency Fluctuations ALFF
Statistical comparisons calculated are defined as primary and secondary outcomes below and include i prediction of treatment outcome reduction in headache days from T0 further PR ii alterations between T0 and T1 iii differences between healthy controls and migraine patients at T0 further HvsPAT and iv differences between responders and non-responder at T0 and T1
In the hypothesis generating Hamburg data significant results at a threshold of cluster-wise FDR-corrected p005 with an entry threshold of voxel-wise uncorrected p0001 when corrected for age and sex in were found
LCOR PR Two clusters in left lateral occipital cortex and right temporal fusiform cortex HvsPAT bilateral thalamus left frontal operculum
SBC Seed to Voxel PR Hypothalamus 2 clusters Sensori Motor Lateral R 1 cluster Visula Lateral L 1 cluster Visual Lateral R 3 cluster HvsPAT Sensori Motor Lateral L 5 cluster Sensori Motor Lateral R 1 cluster Sensori Motor Superior 3 cluster Visual Medial 3 cluster Visual Occipital 1 cluster Visual Lateral L 4 cluster Visual Lateral R 1 cluster
ICA ICA 5 2 cluster ICA 16 2 cluster ICA 28 1 cluster ICA 34 2 cluster HvsPAT ICA 4 3cluster ICA 6 4 cluster ICA 14 4 cluster ICA 18 2 cluster ICA 27 3 cluster ICA 29 14 cluster ICA 33 3 cluster ICA 36 7 cluster ICA 38 6 cluster
There were no significant results for SBC ROI to ROI GCOR and ALFF
There were no significant results for the chosen threshold for the comparisons between responders and non-responder at T0 and T1 Preliminary results for local and global connectivity were recently presented at a scientific conference
To reproduce the significant results from the Hamburg data there is choosen a small volume-corrected threshold of p005 For non-significant result the statistical threshold for the data of the two other sites will be set to voxel-wise FWE-corrected p005
MPRAGE Raw T1-images aka MPRAGE were processed using the CAT12-toolbox httpsneuro-jenagithubiocat12-help which extents SPM12 httpswwwfilionuclacukspmsoftwarespm12 For controls and migraine patients with data from only the first day images segmented into compartments of gray and white matter and normalized For patients with data from 2 days data was longitudinally segmented Images of gray and white matter were smoothed with an isotropic Gaussian kernel of 6 mm3 T-test and F-tests implemented in the SPM12 toolbox were used to estimate significant differences at a threshold of cluster-wise-correct p005 The individual total intracranial volume TIV which is also estimated by the CAT12-toolbox was used as covariate to control for different brain sizes Age and gender were used as further covariates when indicated All results were masked by gray or white matter masks stemming from a segmentation of the average normalized T1s of the participants The statistical threshold for the hypotheses generating data set from Hamburg was set to cluster-wise FDR-corrected p005 with an entry threshold of voxel-wise uncorrected p0001 As no significant results were achieved the statistical threshold for the data of the two other sites will be set to voxel-wise FWE-corrected p005
ASL ASL was not yet analyzed for any of the sites For the statistics we will use Cerebral Perfusion Images stemming from the toolbox ASLtbx httpswwwcfnupenneduzewangASLtbx_manualpdf Nevertheless as different imaging protocols were available in Spain and Italy a comparison of the equality has to be proofen first Therefore we acquired both protocols in the Hamburg data As we do not expect any differences here the statistical threshold will be set to voxel-wise FWE-corrected p005
Power calculation based on Hamburg MR data Power analysis of the primary outcome prediction of headache reduction with resting-state functional connectivity measures from fMRI of day 1 for which rs-fMRI data of 54 migraine patients from the hypothesis generating site Hamburg were analyzed using the CONN-toolbox revealed that 37 migraine patients are necessary to reproduce the result of significant comodulation in local correlation when corrected for age and gender 80 Power FWE-corrected p005 calculated with PowerMap Initial quality checks of the data from the other two sites reveal enough available data for reproduction
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None