Ignite Creation Date:
2024-05-06 @ 7:04 PM
Last Modification Date:
2024-10-26 @ 2:59 PM
Study NCT ID:
NCT05880914
Status:
RECRUITING
Last Update Posted:
2023-07-17
First Post:
2023-05-19
Brief Title:
Precision Medicine Approaches to Renal Osteodystrophy
Sponsor:
Thomas Nickolas MD MS
Organization:
Columbia University
Study Overview
Official Title:
Precision Medicine Approaches to Renal Osteodystrophy
Status:
RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PMaROD
Brief Summary:
Treatment of renal osteodystrophy is impeded by the lack of practical and accurate tools to determine underlying bone turnover Gold standard bone biopsy is not practical in the clinic for the vast majority of kidney disease patients and parathyroid hormone and bone alkaline phosphatase have insufficient accuracy for turnover type to safely and confidently guide treatment of renal osteodystrophy In the present investigation the investigators will study a microRNA approach as a novel non-invasive biomarker of turnover for renal osteodystrophy
Detailed Description:
Renal osteodystrophy ROD is a complex disorder of cortical bone quality and strength Impaired cortical bone is due to the combined actions of elevated parathyroid hormone PTH levels and changes in bone hormones as a result of kidney failure ROD affects nearly all patients with chronic kidney disease CKD and results in cortical bone loss cortical-type fractures and cardiovascular events The current goal of ROD treatment to reduce high bone turnover due to renal hyperparathyroidism is contraindicated in the presence of low turnover yet reliable ways to determine low turnover status are lacking The Kidney Disease Improving Global Outcomes KDIGO guidelines recommend that treatment is guided by the biomarkers PTH and bone specific alkaline phosphatase BSAP and not to treat when turnover is low However despite these recommendations cortical-type fracture incidence has doubled in dialysis patients over the past 25-years a failure in fracture reduction due in part to PTH and BSAP being developed to identify turnover in trabecular rather than cortical bone Furthermore although KDIGO recommends tetracycline-labeled bone biopsy to define turnover and guide treatment the histomorphometry is also based on analysis of trabecular and not cortical bone the latter being the primary site of PTH action Published preliminary data for this proposal suggest that trabecular turnover is a poor surrogate for cortical turnover with only moderate correlations between bone compartments R2 59 Thus there is an unmet need to identify biomarkers with high diagnostic accuracy and clinical utility for the identification of low cortical turnover used without or without trabecular turnover to guide treatment decisions and for use in clinical trials In published data the investigators hypothesized that an a priori defined subset of microRNAs miRNA that regulate osteoblast miRNA-30c 30b 125b and osteoclast miRNA-155 development would be accurate biomarkers of low cortical turnover In 23 CKD patients with bone biopsies the areas under the curve for discrimination of low from non- low turnover were 0866 0813 0813 and 0723 for miRNAs-30b 30c 125b and 155 respectively 0925 for a panel of the 4 four miRNAs combined while PTH and BSAP individually and together did not discriminate in this population Based on these findings the central hypothesis is that circulating miRNAs discriminate ROD cortical bone subtype In a cohort of 90 CKD patients with low normal and high turnover 30group Aim 1 we will use miRNAseq to identify novel miRNAs that correlate with ROD type and determine if their combination with the preliminary panel enhances discrimination In 40 ROD patients managed with strategies that change turnover from high to low or low to high n20group Aim 2 the investigators will determine if changes in histology-based turnover are reflected by changes in the optimized panel and if the circulating miRNA panel mirrors bone-tissue miRNA expression Then the investigators will determine if the panel is related to bone quality and strength Aim 3 The study results will determine if the circulating panel can serve as a biomarker for guiding ROD management This high impact proposal has the potential to result in a paradigm shift in the non-invasive diagnosis and management of ROD
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01DK134101 | NIH | None | httpsreporternihgovquickSearchR01DK134101 |