Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04536103 |
| Other study ID # |
20-599 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 1, 2022 |
| Est. completion date |
December 28, 2026 |
Study information
| Verified date |
March 2024 |
| Source |
The Cleveland Clinic |
| Contact |
Xiaojuan Li, PhD |
| Phone |
510-685-3495 |
| Email |
lix6[@]ccf.org |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Currently the diagnosis of OA is based on radiographs and clinical findings, which is limited
to detecting late-stage disease. There is a pressing, unmet clinical need for robust
assessment of early changes in cartilage health. Towards this goal, extensive efforts are
ongoing to develop quantitative MRI for cartilage matrix analysis. MR T1ρ and T2 relaxation
times have shown to be promising imaging biomarkers for early cartilage degeneration and
prediction of disease progression. However, many challenges remain to clinically applying
these techniques, including lack of standardized acquisition and quantification methods, and
long acquisition times. The study aims to develop novel, fast and reproducible MR T1ρ and T2
relaxation time imaging methods on MR systems from multiple vendors and establish a platform
for standardization and cross validation of these measures as a tool for clinical trials
using such techniques. Following method validation, patients at risk for osteoarthritis will
be tested.
Description:
The significance of this study is twofold. First, one typical hurdle in applying advanced
quantitative MRI to clinical protocols is the long acquisition time. The proposed novel
acceleration techniques will facilitate clinical translations of T1ρ and T2 imaging by
reducing the time and cost to integrate the sequences into standard clinical practice,
increasing patient comfortableness and reducing potential motion artifacts. Second, it is an
essential but sometimes overlooked step to investigate quantification variability across
sites and MR systems in order to validate MR imaging biomarkers and to apply the measures in
large scale multi-vendor multi-site trials. Specifically, there is a lack of systematic
evaluation of inter-vendor inter-site variability of T1ρ imaging even though it has been
widely applied in neural imaging, liver imaging, cardiac imaging, oncology imaging, and
musculoskeletal imaging. Furthermore, no commercial T1ρ phantoms are available with validated
reference values. The proposed study is addressing these significant gaps. By implementing
and cross-validating T1ρ and T2 imaging on MR systems from different vendors, the outcomes
from the proposed study (dedicated calibration phantoms, fast and standardized acquisition
and analysis protocols) will provide the field with essential tools for future multi-vendor
multi-site trials that will use these quantitative imaging techniques. In this proposal, the
innovation and development in patients at risk for osteoarthritis will be tested.
In this study, novel accelerated T1ρ and T2 imaging methods will be developed to
systematically evaluate inter-vendor inter-site variation of these measures using dedicated
T1ρ and T2 calibration phantoms (to be developed in this study) and traveling subjects, and
demonstrate the feasibility in patients after ACL injury and reconstruction who are at risk
of post-traumatic OA. The investigation has three Specific Aims:
1. - Develop novel acceleration techniques for fast 3D T1ρ and T2 imaging. Despite the
increasing availability of accelerated morphologic imaging using compressed sensing (CS)
techniques, applications of CS to quantitative MRI are still very limited with the
challenges of maintaining quantitative accuracy. A novel convex, model-based CS
technique will be developed to take full advantage of the known model for T1ρ and T2
decay.
2. - Develop a calibration phantom suitable for standardization of T1ρ and T2 measurements
and implement acceleration techniques on MR systems of three major vendors (Siemens, GE
and Philips). The phantom development and reference measurements will be in
collaboration with the National Institute of Standards and Technology (NIST). The
accelerated T1ρ and T2 sequences will be implemented on six MR systems at four sites
from three vendors. Inter-site and inter-vendor variation of T1ρ and T2 will be
quantified in phantoms and traveling human subjects.
3. - Demonstrate the ability of the newly developed acceleration techniques to quantify
cartilage degeneration longitudinally in a multi-vendor setting. Subjects with acute
anterior cruciate ligament (ACL) tears, an established 'early OA' model, along with
age-, gender-, and BMI-matched controls will be scanned on three MR systems using
standard and accelerated T1ρ and T2 protocols at baseline and one-year. A novel
atlas-based voxel-based relaxometry (VBR) analysis will be applied. Cross-sectional and
longitudinal measures will be compared between standard and accelerated T1ρ and T2
protocols.
Four groups of subjects will be recruited at CCF for the study.
Group I: 30 volunteers (for Aim 1) The 30 volunteers from Group I will be recruited at CCF
for evaluating differences between standard T1rho and T2 imaging vs accelerated T1rho and T2
imaging techniques that will be developed from this study.
Group II: 8 traveling volunteers (for Aim 2) The 8 traveling volunteers in Group II will be
recruited at CCF and be scanned at CCF, University of California San Francisco, University of
Kentucky and Albert Einstein College of Medicine.
Group III: 30 patients with acute ACL tears (for Aim 3) Group IV: 12 controls who are matched
with Group III patients with age, sex and BMI (for Aim 3) Subjects in group III and IV will
be recruited at CCF and scanned at baseline and 1-year at all of the three MR systems at CCF
(Siemens, GE, Philips).
Subjects of Group I will be recruited in year 1 and 2; Group II will be recruited in year 2
and 3, and Group III and IV will be recruited in year 3-5. Group II and IV share the same
inclusion and exclusion criteria, therefore subjects can participate the study and serve as
subjects within both groups.
At two other sites involved in the study, University of California San Francisco (UCSF) and
Albert Einstein College of Medicine at New York, 20 local volunteers will be recruited for
sequence development in year 1 and 2.
