Renal OsteodystrophyPMaRODNCT05880914
Precision Medicine Approaches to Renal Osteodystrophy
An observational study of Renal Osteodystrophy and Chronic Kidney Diseases, run by Thomas Nickolas at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Osteodystrophy, Chronic Kidney Diseases, CKD-MBD
- What is being tested?
- miRNAseq analysis and Standard treatment for bone disorder
- Type of treatment
- Surgery or procedure
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Dec 2022to 30 Jun 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: This study will enroll forty adults with moderate to end stage kidney disease, including kidney transplant recipients, who have bone disease in need of treatment.
Who may be able to join
- Study participant has provided informed consent
- Age ≥ 18 years
- CKD Stages 3-5D regardless of kidney transplantation status
- CKD5D patients receiving maintenance hemodialysis for at least 3 months
- Clinically indicated treatment for renal hyperparathyroidism, renal osteodystrophy and/or Osteoporosis
- PTH, BSAP and CTX meets defined thresholds for low or high turnover ROD type or a Bone biopsy evidence of low or high turnover based
Who cannot join
- Currently receiving treatment in an investigational device or drug study, or less than 30 days since ending treatment on an investigational device or drug study(s)
- Currently receiving investigational procedures/drugs from another study while participating in this study
- Use of etelcalcetide, bisphosphonate, denosumab, teriparatide, abaloparatide or romosozumab during the 6 months prior to study enrollment; however, participant can be included if being treated with bone active agent but will have class change to an agent that will result in a change in bone turnover from low to high or high to low
- New use of cinacalcet over the prior 6 months
- Use of Zoledronic Acid (Reclast) less than 24 months from study enrollment for patients with eGFR <30mL/minute
- Anticipated or scheduled kidney transplant during the study period or less than 1 year from receiving a kidney transplant
Show all 16Show fewer
- For patients with a solid organ transplant, less than 1 year from receiving the transplant
- Patient has an unstable medical condition based on medical history, physical examination, and routine laboratory tests, or is otherwise unstable in the judgment of the Investigator
- Metabolic bone diseases not related to the kidney (e.g., Paget's, Osteogenesis Imperfecta)
- Endocrinopathy (e.g., untreated hyperthyroidism)
- Malignancy within the last 5 years (except non-melanoma skin cancers or cervical carcinoma in situ)
- Patient is pregnant or nursing
- Weight >300 pounds (scanner limitation)
- Allergy to tetracycline or demeclocycline
- Patients on non-aspirin anticoagulants that cannot be reasonably held for biopsy
- Patient unable to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the patient and Investigator's knowledge
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Washington University in St. Louis (WashU)
St Louis, Missouri, 63110
Thomas L Nickolas, MD MS, 212-305-9847, thomasn@wustl.edu
Maria Alejandra Aponte, MD, 314-273-8827, mariaalejandra@wustl.edu
About this study
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.
Read the 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 0.866, 0.813, 0.813, and 0.723 for miRNAs-30b, 30c, 125b and 155 respectively, 0.925 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 (30/group; 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 (n=20/group; 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.
- Conditions
- Renal Osteodystrophy, Chronic Kidney Diseases, CKD-MBD, Bone Turnover Rate Disorder, Secondary Hyperparathyroidism
- Being tested
- miRNAseq analysis, Standard treatment for bone disorder
- Keywords
- Bone biopsy, microRNA, HR-pQCT, Bone biomarkers, Bone imaging
- Medical subject headings
- Chronic Kidney Disease-Mineral and Bone Disorder, Renal Insufficiency, Chronic, Hyperparathyroidism, Secondary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
miRNAseq analysisProcedure or surgery
Identify miRNA in serum and prepare a miRNA sequencing library for novel analysis.
Standard treatment for bone disorderDrug
Also called Clinically indicated treatment for bone disease
Participants will be prescribed a clinically indicated bone-targeted treatment for osteoporosis or bone disorder related to CKD. (non-experimental)
| Study group | Role | What they receive |
|---|---|---|
| Bone-targeted management - prospective cohort | Participants diagnosed with a bone disorder related to chronic kidney disease (CKD) and undergoing a clinically indicated treatment for bone disease. Participants will have some questionnaires, research blood draws, bone scans and a bone biopsy. There will be a total of 4 visits over six months for data collection. Receives: Procedure: miRNAseq analysis; Drug: Standard treatment for bone disorder |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation between miRNA panel to discriminate changes in bone turnover.
To determine the utility of a miRNA panel to discriminate changes in bone turnover. miRNA sequencing libraries will be prepared using the QIASeq miRNA Library Kit (Qiagen). Total RNA extracted from human serum will be used as the starting material. After a final library cleanup, the miRNA libraries will be QC and quantified using an Agilent Bioanalyzer 2100 and Invitrogen Qubit Fluorometer. The resulting miRNA libraries will be sequenced on an Illumina NextSeq 500 (Illumina, San Diego, CA) with single-end 75 bp read length. The study will then confirm any novel or other miRNA that are present in serum from RNAseq by PCR using TaqMan miRNA Assays (TaqMan MGP probes, FAM dye-labeled) with Applied Biosystems ViiA 7 Real-Time PCR systems. The ΔΔCT method will be used to analyze relative changes in miRNA expression.
Measured: Five years
Correlation between a miRNA panel that identifies bone turnover type is able to also identify with bone quality.
To utilize the circulating miRNA panel to fully assess bone quality in patients with renal osteodystrophy; whether there is evidence that bone turnover directly affects bone strength through alterations in bone quality.
Measured: Five Years
Secondary outcomes (2)
Number of instances where miRNAs in circulation reflect miRNAs in bone-tissue.
The miRNA panel that identifies turnover type in blood will be compared to the miRNAs that are expressed in bone tissue derived from iliac crest bone biopsy.
Measured: Five Years
Number of instances where miRNAs in circulation reflect changes in bone, based on bone imaging.
Pre- and post-treatment changes in the circulating miRNA profile will be compared to changes in bone imaging by HR-pQCT.
Measured: Five Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2023
- Study start21 Dec 2022
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Renal OsteodystrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Thomas Nickolas
- Sponsor type
- University, hospital or other
- Collaborators
- Indiana University, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Sponsor-investigator, Thomas Nickolas, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05880914
- Sponsor's protocol ID
- 202503010-AAAU1119
- Other IDs
- R01DK134101
- Acronym
- PMaROD
- Status last verified
- Jun 2026
- First submitted
- 19 May 2023
- Last updated
- 12 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The investigator is currently not planning on providing IPD to other researchers but may modify his plans in the future. All IPD would be de-identified and provided after justification from the corresponding investigator.
Publications
Nickolas TL, Chen N, McMahon DJ, Dempster D, Zhou H, Dominguez J 2nd, Aponte MA, Sung J, Evenepoel P, D'Haese PC, Mac-Way F, Moyses R, Moe S. A microRNA Approach to Discriminate Cortical Low Bone Turnover in Renal Osteodystrophy. JBMR Plus. 2020 Mar 25;4(5):e10353. doi: 10.1002/jbm4.10353. eCollection 2020 May.
PubMed 32490328
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Precision Medicine Approaches to Renal Osteodystrophy
- ClinicalTrials.gov ID
- NCT05880914
- Acronym / sponsor ID
- PMaROD / 202503010-AAAU1119
- Conditions
- Renal Osteodystrophy, Chronic Kidney Diseases, CKD-MBD, Bone Turnover Rate Disorder, Secondary Hyperparathyroidism
- Keywords
- Bone biopsy, microRNA, HR-pQCT, Bone biomarkers, Bone imaging
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Thomas NickolasUniversity, hospital or other
- Collaborators
- Indiana University, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 21 Dec 2022 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 30 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 0.866, 0.813, 0.813, and 0.723 for miRNAs-30b, 30c, 125b and 155 respectively, 0.925 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 (30/group; 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 (n=20/group; 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 design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bone-targeted management - prospective cohort | – | Procedure: miRNAseq analysis, Drug: Standard treatment for bone disorderParticipants diagnosed with a bone disorder related to chronic kidney disease (CKD) and undergoing a clinically indicated treatment for bone disease. Participants will have some questionnaires, research blood draws, bone scans and a bone biopsy. There will be a total of 4 visits over six months for data collection. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- This study will enroll forty adults with moderate to end stage kidney disease, including kidney transplant recipients, who have bone disease in need of treatment.
Key inclusion criteria (6 listed)
- Study participant has provided informed consent
- Age ≥ 18 years
- CKD Stages 3-5D regardless of kidney transplantation status
- CKD5D patients receiving maintenance hemodialysis for at least 3 months
- Clinically indicated treatment for renal hyperparathyroidism, renal osteodystrophy and/or Osteoporosis
Key exclusion criteria (16 listed)
- Currently receiving treatment in an investigational device or drug study, or less than 30 days since ending treatment on an investigational device or drug study(s)
- Currently receiving investigational procedures/drugs from another study while participating in this study
- Use of etelcalcetide, bisphosphonate, denosumab, teriparatide, abaloparatide or romosozumab during the 6 months prior to study enrollment; however, participant can be included if being treated with bone active agent but will have class change to an agent that will result in a change in bone turnover from low to high or high to low
- New use of cinacalcet over the prior 6 months
- Use of Zoledronic Acid (Reclast) less than 24 months from study enrollment for patients with eGFR <30mL/minute
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| miRNAseq analysisIdentify miRNA in serum and prepare a miRNA sequencing library for novel analysis. | Procedure or surgery | Bone-targeted management - prospective cohort |
| Standard treatment for bone disorderAlso: Clinically indicated treatment for bone diseaseParticipants will be prescribed a clinically indicated bone-targeted treatment for osteoporosis or bone disorder related to CKD. (non-experimental) | Drug | Bone-targeted management - prospective cohort |
Primary outcome
Correlation between miRNA panel to discriminate changes in bone turnover.
Time frame: Five years
To determine the utility of a miRNA panel to discriminate changes in bone turnover. miRNA sequencing libraries will be prepared using the QIASeq miRNA Library Kit (Qiagen). Total RNA extracted from human serum will be used as the starting material. After a final library cleanup, the miRNA libraries will be QC and quantified using an Agilent Bioanalyzer 2100 and Invitrogen Qubit Fluorometer. The resulting miRNA libraries will be sequenced on an Illumina NextSeq 500 (Illumina, San Diego, CA) with single-end 75 bp read length. The study will then confirm any novel or other miRNA that are present in serum from RNAseq by PCR using TaqMan miRNA Assays (TaqMan MGP probes, FAM dye-labeled) with Applied Biosystems ViiA 7 Real-Time PCR systems. The ΔΔCT method will be used to analyze relative changes in miRNA expression.
Correlation between a miRNA panel that identifies bone turnover type is able to also identify with bone quality.
Time frame: Five Years
To utilize the circulating miRNA panel to fully assess bone quality in patients with renal osteodystrophy; whether there is evidence that bone turnover directly affects bone strength through alterations in bone quality.
2 secondary outcomes
Number of instances where miRNAs in circulation reflect miRNAs in bone-tissue.
Time frame: Five Years
Number of instances where miRNAs in circulation reflect changes in bone, based on bone imaging.
Time frame: Five Years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2026.
- Background: PubMed 32490328Nickolas TL, Chen N, McMahon DJ, Dempster D, Zhou H, Dominguez J 2nd, Aponte MA, Sung J, Evenepoel P, D'Haese PC, Mac-Way F, Moyses R, Moe S. A microRNA Approach to Discriminate Cortical Low Bone Turnover in Renal Osteodystrophy. JBMR Plus. 2020 Mar 25;4(5):e10353. doi: 10.1002/jbm4.10353. eCollection 2020 May.
- Individual participant dataSharing planned: No. The investigator is currently not planning on providing IPD to other researchers but may modify his plans in the future. All IPD would be de-identified and provided after justification from the corresponding investigator.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Renal Osteodystrophy and Chronic Kidney Diseases, run by Thomas Nickolas at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation between miRNA panel to discriminate changes in bone turnover. (time frame: Five years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05880914, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2026.