Genetic Regulators of Bone Health That Are Unique to Vertebral Bone

April 2, 2024 updated by: University of Colorado, Denver

Identification and Characterization of Genetic Regulators of Bone Health That Are Unique to Vertebral Bone.

Osteoporosis is an age related disease in which a person's bone slowly becomes weaker with time. The bones may become so weak that they break easily such as a fall from standing height. The most commonly broke bones in osteoporosis are those of the hip, the spine or the wrist. Osteoporosis runs in families meaning that genetic differences explain why some people break bones in old age and other do not. Genetic studies have been done that show the the genes associated with spine (vertebral) fractures (broken bones) and hip fractures are different, suggesting that osteoporosis of the spine is not the exact same disease as osteoporosis of the hip. Genetic studies tell us what part of the genome (i.e. genes) are associated with a disease, but do not tell us how these genes act biologically to cause that disease. In this study, we seek to determine how the genes uniquely associated with spine osteoporosis behave in normal and aged bone, to determine how they interact with each other as a team to impact spine bone. In this study, we will measure gene activity (so called gene expression) in bone samples taken from people undergoing major spine deformity surgery. We will using genetic data from these patients to determine how gene activity is controlled in bone and how that relates to measures of bone health such as bone mineral density data. The results of this study will provide critical data regarding how osteoporosis of the spine happens, and these data will be used to find better and safer treatments to prevent bone fractures of the spine that happen with age.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
550

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • Univeristy of Colorado Denver
        • Contact:
        • Contact:
        • Principal Investigator:
          • Cheryl L Ackert-Bicknell, PhD
        • Principal Investigator:
          • David Ou Yang, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients undergoing deformity correction surgery undergoing a multi-level spinal fusion (i.e. a T10 (or higher) fusion to the pelvis) -OR- a 3 column osteotomy with a corpectomy from for short segment surgeries -OR- a vertebral column resection (VCR) involving a corpectomy -OR- any deformity correction surgery wherein the attending surgeon determines that a large amount of bone containing trabecular elements will be removed and discarded. Patients Patients will be recruited through the Spine Center at the University of Colorado Hospital.

Description

Inclusion Criteria:

  • Men and women between the ages of 18 and 85 undergoing a multi-level spinal fusion (i.e. a T10 (or higher) fusion to the pelvis) -OR- a 3 column osteotomy with a corpectomy from for short segment surgeries -OR- a vertebral column resection (VCR) involving a corpectomy -OR- any deformity correction surgery wherein the attending surgeon determines that a large amount of bone containing trabecular elements will be removed and discarded.
  • Willing and able to provide informed consent

Exclusion Criteria:

  • End stage renal disease.
  • Any history of cancer.
  • Reliance on a wheelchair for 70% or greater of their mobility for longer than 12 months.
  • Quadra or paraplegia due to spinal cord injury.
  • Current use of epilepsy medications.
  • Confirmed Marfans, osteogenesis imperfecta or other genetic syndrome known to impact bone formation (Guacher's, Vit D independent rickets, etc).
  • Current glucocorticoid use lasting longer than 3 months, or greater than 6 months lifetime use.
  • Current or suspected current infection associated with orthopedic hardware.
  • HIV or Hep C positive and or currently on anti-viral medications.
  • History of gastric bypass surgery and or weigh loss exceeding 100 pounds.
  • Primary or secondary hyperparathyroidism.
  • Paget's disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Patients undergoing deformity correction surgery
Patients undergoing deformity correction surgery undergoing a multi-level spinal fusion (i.e. a T10 (or higher) fusion to the pelvis) -OR- a 3 column osteotomy with a corpectomy from for short segment surgeries -OR- a vertebral column resection (VCR) involving a corpectomy -OR- any deformity correction surgery wherein the attending surgeon determines that a large amount of bone containing trabecular elements will be removed and discarded
Other: Sample collection for gene expression
This is a cross-sectional sample collection study. Vertebral bone tissue that would otherwise be discarded is collected from patients undergoing surgery to correct a spine deformity and gene expression is measure in these tissues.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Gene and transcript quantification
Time Frame: Baseline
The abundances (in transcripts per million, TPM) of all known transcripts will be quantified in each bone sample via next generation RNA-sequencing.
Baseline
Genotypes
Time Frame: Baseline
Low coverage whole genome sequence data will be obtained from all participants and the yielded outcome will be high quality genotypes for millions of single nucleotide polymorphism (SNPs) across the patient's genome. As this is low coverage genotyping, the coverage rate will be between 1 and 0.4X representation for each spot in the genome per patients, so the data will be imputed to ensure coverage to 1X for all patients. Each patient will be genotyped and therefore, data on a per participant level will be yielded.
Baseline

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Expression quantitative trait loci (eQTL)
Time Frame: Baseline
Using the imputed genotyping data and the gene expression data, regions of the genomes where there is local control (so called cis-regulatory elements) of for each gene expressed in bone will be identified. The outcome deliverable will be a list of genes for which there is local genetic control of that gene's expression and the single nucleotide polymorphism(s) likely to be involved. Each entry in this list is an Expression quantitative trait loci (eQTL). This analysis uses all data from all participants in aggregate and the yielded results will be at the level of averages for the cohort, not at the individual participant level.
Baseline
Co-localization
Time Frame: Baseline
Expression quantitative trait loci that co-localize with previously published bone mineral density genome wide association study associations will be identified. Co-localizing genes will be prioritized for additional analyses. This analysis uses all data from all participants in aggregate and the yielded results will be at the level of averages for the cohort, not at the individual participant level.
Baseline
Expression-phenotype correlation
Time Frame: Baseline
For the genes for which a prioritized Expression quantitative trait loci from the co-localization analysis was identified, bone mineral density and other measures of bone mass and quality will be will be tested for correlation with the gene expression measures. This analysis uses all data from all participants in aggregate and the yielded results will be at the level of averages for the cohort, not at the individual participant level.
Baseline
Co-expression Network
Time Frame: Baseline
The participant level gene expression data, as collected from bone samples, will be used to construct networks of gene-gene interaction. This will yield modules of highly correlated gene expression. Bone mineral density data obtained from the patient electronic medical record will be used to identify modules that correlate with bone mineral density.This analysis uses all data from all participants in aggregate and the yielded results will be at the level of averages for the cohort, not at the individual participant level.
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Colorado, Denver

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Virginia

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Cheryl L Ackert-Bicknell, PhD, University of Colorado, Denver

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 30, 2030

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 30, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 7, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 7, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 14, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 3, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 2, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 23-0602

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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