Evaluation and Management of Metabolic Bone Disease in Kidney Transplant Recipients

There is a well-documented increased risk for disordered mineral bone homeostasis in Kidney Transplant Recipients (KTRs) when compared to the general population, leading to a markedly increased risk for fragility fractures and their associated morbidity and mortality. A more uniform and rigorous evaluation of bone and mineral homeostasis,than is afforded to patients under "normal care", will result in better clinical outcomes in KTRs.

Study Overview

• Status: Completed
• Conditions: Kidney Transplant; Complications; Skeletal Anomalies
• Intervention / Treatment: Diagnostic test: measurements to evaluate metabolic bone disease; Diagnostic test: standard care

Detailed Description

The aim is to comprehensively characterize the mineral metabolism and skeletal phenotype in kidney transplant recipients (KTRs) to being to identify risk factors for post-kidney transplant mineral bone disease (PKT-MBD); and to evaluate whether treatment of abnormalities in these parameters will improve skeletal health as quantified by bone mineral density (BMD), bone turnover markers (rate of skeletal remodeling) and Osteoprobe (a direct index of bone quality using reference point indentation technology.

Participants in the rigorous evaluation arm will be followed with a) Mineral metabolism: blood calcium, phosphorus, parathyroid hormone (PTH), 25(OH) vitamin D; b) Bone turnover markers: bone-specific alkaline phosphatase, cross-linked C-telopeptide of type I collagen (CTx), and N-terminal propeptide of type I collagen (PINP); c)Bone Mineral Density using a Dual energy x-ray absorptiometry which is the standard method by which bone mass is measured clinically.

NOTE: The use of the Osteoprobe was discontinued on 9/5/19 due to safety concerns from the FDA about the device in other trials/other sites.

The Control Cohort is essentially an historical control group who will have received standard of care for the 18 months ending just prior to the enrollment of our Intervention Cohort. A coincident Control Cohort will not be used because knowledge of the additional data to be collected in the Control Cohort will undoubtedly influence their care by their attending nephrologists and surgeons.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Renata Belfort De Aguiar, PhD,MD; Phone Number: 203-785-7474; Email: renata.aguiar@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Transplantation Center/Yale-New Haven Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Kidney transplant subjects within the first 3 months after surgery (intervention cohort) and 18 months after surgery (control cohort)
• Age between 30 to 65 years old
• Estimated glomerular filtration rate (GFR) > 35 ml/min/1.73 m2

Exclusion Criteria:

• Major acute post-operatory complications (infection, urine leak, delayed graft function)
• Living related-donor KTRs
• Estimated GFR ≤ 35 ml/min/1.73 m2
• Significant skin disorder, bruising, local edema, skin infection or are being treated with anticoagulants (such as warfarin, heparin, low molecular weight heparin or direct thrombin inhibitors) or have known or acquired clotting disorders since the OsteoProbe® procedure would be unsafe
• Patients who do not plan to be followed at Yale New Haven for at least 18 months
• Morbidly obese (BMI >40)
• History of gastroparesis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rigorous evaluation; Participants will be evaluated for the rigorous evaluation received.	Diagnostic test: measurements to evaluate metabolic bone disease; The participants will be evaluated for a) Mineral metabolism: blood calcium, phosphorus, PTH, 25(OH) vitamin D; b) Bone turnover markers: bone-specific alkaline phosphatase, cross-linked C-telopeptide of type I collagen (CTx), and N-terminal propeptide of type I collagen (PINP); c) Bone Mineral Density using a Dual energy x-ray absorptiometry which is the standard method by which bone mass is measured clinically. The bone mass at the lumbar spine, wrist, hip and total body bone mass at 3, and 18 months.
Active Comparator: Standard care; The participants will be evaluated for the standard of care received.	Diagnostic test: standard care; Blood tests (Ca, Phos, PTH- mineral lab, 25OHVitD);Pregnancy Test (if applicable); dual energy X-ray absorptiometry (DXA); Bone Biopsy only if clinically indicated; treatment as clinically indicated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in bone turnover marker carboxy-terminal collagen crosslinks (CTx)	In the intervention group changes in measures of mineral metabolism (serum calcium, phosphorus, PTH and 25 OH vitamin D levels), changes in bone turnover markers, BMD and bone quality markers will be compared to baseline results. The primary outcome variable will be the change in serum CTx from baseline. CTx is a marker of bone resorption and rates of resorption predict bone loss and fracture risk.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variance in bone loss	the changes in PTH, CTx, Procollagen Type 1 N-Terminal Propeptide (P1NP), Trabecular Bone Score (TBS) and Bone Material Strength Index (BMSi) will be correlated with changes in bone mineral density (BMD) in a multiple regression model to determine their contributions to the variance in rates of bone loss. This will serve to inform our planned prospective study in terms of what measures to follow.	18 months

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Renata Belfort de Aguiar, Phd,MD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2018
• Primary Completion (Actual): December 2, 2021
• Study Completion (Actual): December 2, 2021

Study Registration Dates

• First Submitted: May 16, 2019
• First Submitted That Met QC Criteria: May 16, 2019
• First Posted (Actual): May 22, 2019

Study Record Updates

• Last Update Posted (Estimate): February 28, 2023
• Last Update Submitted That Met QC Criteria: February 24, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic
• Other Study ID Numbers: 2000022066

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No