A Study to Assess Metabolic Bone Disease of Prematurity Using an Acoustic Method

Assessment of Metabolic Bone Disease of Prematurity Using an Acoustic Method

The goal of this project is to develop a new noninvasive ultrasound based technique, called vibro-acoustic analysis (VAA), for evaluation of infant bone health with particular application in assessment of bone health in premature infants who are at risk for bone disease.

Study Overview

• Status: Completed
• Conditions: Osteopenia; Metabolic Bone Disease; Neonatal Rickets
• Intervention / Treatment: Diagnostic test: Vibro-acoustic analysis (VAA), based on ultrasound radiation force

Detailed Description

With increased survival of very low birth weight and premature infants over recent decades, bone assessment has become especially vital with the recognition of metabolic bone disease (MBD) of prematurity. Bone assessment became especially vital during last decades with the growing emphasis on metabolic bone disease of prematurity and low-birth-weight infants. Statistics shows that up to 50% of low birth weight and preterm newborns are likely to develop metabolic bone disease. Currently, no screening test has been shown to provide both sensitive and specific evidence of developing MBD over the first several weeks of life in the premature infants. Therefore, there is a need for a non-invasive tool for evaluation of infant bone health. This study will be conducted on premature infants at risk for MBD at multiple time points during their growth, with full term infants as controls. vibro-acoustic analysis (VAA) measurements will be done on the tibia. VAA measurements for the premature infants will be compared to those of full term infants. Performance of VAA in identifying osteopenia and its ability to monitor the response to treatment will be evaluated. The investigators will use an ultrasound system that has been used in the pilot study and employ a transducer with a smaller footprint for pediatric application.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 days to 8 months (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Full term newborns, approximately equal number of male and female newborn, age <28 days.
• Preterm infants, approximately equal number of male and female preterm infants with gestational age at birth <37 weeks or birth weight <1500 grams.

Exclusion Criteria:

• Infants currently requiring continuous cardiovascular medication infusions, including but not limited to, dopamine, epinephrine, milrinone, and dobutamine (may have received these medications in the past.
• Infants with major congenital anomalies that may affect bone health or structure.
• For full term infants, infants with a history of intrauterine growth restriction or who are small for gestational age (<10th percentile for weight) at birth.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: premature infants and full term infants; The study visits will be at ≥3 time points at ages: within the first 28 days after birth, 2 months, 3 months, and, if still hospitalized, at 4 months and at 6 months.; The ultrasound machine to the nursery or neonatal intensive care unit at a scheduled time.; The appropriate ultrasound probe will be placed on the infant's tibia and a miniature hydrophone near the probe. A series of ultrasound measurements will be obtained and the ultrasound data will be saved for offline processing.; The Investigators will repeat the measurement in 3 locations of the infant's tibia.; Each ultrasound measurement takes a few seconds. The complete ultrasound study will take about 15 minutes at each visit.; All procedures will be conducted in the nursery or neonatal intensive care unit to ensure infant safety.; The ultrasound measurement for full-term infants can be done in ultrasound lab.

Diagnostic test: Vibro-acoustic analysis (VAA), based on ultrasound radiation force; The study will develop and validate a new ultrasonic method for assessment of infant bone by evaluating structural and mechanical characteristics of the infant tibia. This project will utilize a novel, non-invasive method, vibro-acoustic analysis (VAA), to evaluate infant bone properties in a wide frequency range while reducing the artifacts from soft tissue.; Other Names: ultrasound

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ultrasound Transducer Compatibility	Successful acquisition and integration of a pediatric transducer with a footprint ≤ X cm² and focal depth ≤ Y mm (to be defined based on commercial availability and anatomical feasibility).	1 year
Hydrophone Sensitivity and Size	Selection and validation of a miniature hydrophone (e.g., diameter ≤ Z mm) with high sensitivity, characterized by its frequency response and minimum detectable pressure level.	1 year
Bandwidth Assessment	Measurement of hydrophone bandwidth (in MHz) as a primary indicator of sensitivity and signal capture quality.	1 year
System Performance Metrics	Quantitative assessment of signal-to-noise ratio (SNR) and resolution improvements compared to the previous setup using standard adult-sized components.	1 year
Feasibility in Preclinical Models	Demonstration of the optimized VAA system's ability to produce high-resolution, reproducible images in a neonatal bone phantom or relevant preclinical model.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative Bone Health Index (BHI)	Derived from vibro-acoustic assessment (VAA) of the tibia in both term and preterm infants, BHI will be compared across age-adjusted groups to determine baseline differences between preterm and term infants.	through the study completion, up to 3 years
VAA Sensitivity to Gestational Age	Correlation of VAA-derived parameters with gestational age at birth to assess the method's sensitivity in detecting bone development differences attributable to prematurity.	through the study completion, up to 3 years
Longitudinal Changes in VAA Measurements	Assessment of VAA parameter changes over serial visits in preterm infants undergoing standard nutritional or medical interventions. Evaluates VAA's ability to detect improvements or deteriorations in bone status over time.	through the study completion, up to 3 years
Comparison with Clinical Markers (if available)	Cross-validation of VAA findings with available clinical or biochemical markers of bone health (e.g., serum calcium, phosphate, ALP levels) to evaluate concurrent validity.	through the study completion, up to 3 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Azra Alizad, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2020
• Primary Completion (Actual): August 31, 2024
• Study Completion (Actual): August 31, 2024

Study Registration Dates

• First Submitted: February 2, 2021
• First Submitted That Met QC Criteria: February 8, 2021
• First Posted (Actual): February 12, 2021

Study Record Updates

• Last Update Posted (Actual): April 27, 2025
• Last Update Submitted That Met QC Criteria: April 22, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: ultrasound; Pediatrics; Bone Diseases; Premature; Fracture; Neonatal; Rickets; bone health; infancy; Low Birth Weight Infant; mineralization
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nutrition Disorders; Metabolic Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Calcium Metabolism Disorders; Vitamin D Deficiency; Bone Diseases; Bone Diseases, Metabolic; Rickets
• Other Study ID Numbers: 19-001498; 1R21AR075370-01A1 (U.S. NIH Grant/Contract); 5R21AR075370-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No