Precision Medicine Approaches to Renal Osteodystrophy

NCT05880914 | Recruiting DMC

• 2 other identifiers: 202503010-AAAU1119R01DK134101
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Osteodystrophy; Chronic Kidney Diseases; CKD-MBD; Bone Turnover Rate Disorder; Secondary Hyperparathyroidism

Keywords

Bone biopsy; microRNA; HR-pQCT; Bone biomarkers; Bone imaging

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Five Years

Secondary Outcomes (2)

• Number of instances where miRNAs in circulation reflect miRNAs in bone-tissue.

  Five Years

• Number of instances where miRNAs in circulation reflect changes in bone, based on bone imaging.

  Five Years

Study Arms (1)

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.

Procedure: miRNAseq analysis; Drug: Standard treatment for bone disorder

Interventions

miRNAseq analysis PROCEDURE

Identify miRNA in serum and prepare a miRNA sequencing library for novel analysis.

Bone-targeted management - prospective cohort

Standard treatment for bone disorder DRUG

Participants will be prescribed a clinically indicated bone-targeted treatment for osteoporosis or bone disorder related to CKD. (non-experimental)

Also known as: Clinically indicated treatment for bone disease

Bone-targeted management - prospective cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Thomas Nickolas: lead
• Indiana University School of Medicine: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Washington University in St. Louis (WashU)

St Louis, Missouri, 63110, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 32490328 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood will be stored for future studies that may involve genomic analysis

MeSH Terms

Conditions

Chronic Kidney Disease-Mineral and Bone Disorder; Renal Insufficiency, Chronic; Hyperparathyroidism, Secondary

Condition Hierarchy (Ancestors)

Rickets; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Calcium Metabolism Disorders; Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Hyperparathyroidism; Parathyroid Diseases; Endocrine System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Renal Insufficiency

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: May 19, 2023
• First Posted: May 30, 2023
• Study Start: December 21, 2022
• Primary Completion (Estimated): August 17, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: June 27, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)