Age-Related OsteoporosisNCT05946278
Genetic Regulators of Bone Health That Are Unique to Vertebral Bone
An observational study of Age-Related Osteoporosis, run by University of Colorado, Denver at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Age-Related Osteoporosis
- What is being tested?
- Sample collection for gene expression
- How many people
- 550 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2024to 30 Aug 2030
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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).
Show all 12Show fewer
- 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
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
Univeristy of Colorado Denver
Aurora, Colorado, 80045
Cheryl L Ackert-Bicknell@cuAnschutz.edu, PhD, 303-724-6623, cheryl.ackert-bicknell@cuanschutz.edu
Reed A Ayers, PhD, 303-724-1158, reed.ayers@cuanschutz.edu
About this study
Official title: 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.
- Conditions
- Age-Related Osteoporosis
- Being tested
- Sample collection for gene expression
- Keywords
- Bone mineral density, gene transcription, spine, genetic disease
- Medical subject headings
- Osteoporosis, Genetic Diseases, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sample collection for gene expressionOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Other: Sample collection for gene expression |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gene and transcript quantification
The abundances (in transcripts per million, TPM) of all known transcripts will be quantified in each bone sample via next generation RNA-sequencing.
Measured: Baseline
Genotypes
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.
Measured: Baseline
Secondary outcomes (4)
Expression quantitative trait loci (eQTL)
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.
Measured: Baseline
Co-localization
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.
Measured: Baseline
Expression-phenotype correlation
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.
Measured: Baseline
Co-expression Network
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.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2023
- Study startApr 2024 (estimated)
- Primary completion30 Aug 2030 (estimated)
- Study completion30 Aug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Age-Related OsteoporosisStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- 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
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 550 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- University of Virginia
- Responsible party
- Sponsor
- Investigators
- Cheryl L Ackert-Bicknell, PhD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05946278
- Sponsor's protocol ID
- 23-0602
- Status last verified
- Apr 2024
- First submitted
- 7 Jul 2023
- Last updated
- 3 Apr 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification and Characterization of Genetic Regulators of Bone Health That Are Unique to Vertebral Bone.
- ClinicalTrials.gov ID
- NCT05946278
- Acronym / sponsor ID
- 23-0602
- Conditions
- Age-Related Osteoporosis
- Keywords
- Bone mineral density, gene transcription, spine, genetic disease
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 550 participants (estimated)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- University of Virginia
- Study start
- Apr 2024 (estimated)
- Primary completion
- 30 Aug 2030 (estimated)
- Study completion
- 30 Aug 2030 (estimated)
- First posted
- 14 Jul 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.
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 design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients undergoing deformity correction surgery | – | Other: Sample collection for gene expressionPatients 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 |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (12 listed)
- 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.
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 |
|---|---|---|
| Sample collection for gene expressionThis 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. | Other | Patients undergoing deformity correction surgery |
Primary outcome
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.
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.
4 secondary outcomes
Expression quantitative trait loci (eQTL)
Time frame: Baseline
Co-localization
Time frame: Baseline
Expression-phenotype correlation
Time frame: Baseline
Co-expression Network
Time frame: Baseline
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 3 Apr 2024.
- Individual participant dataSharing planned: Undecided
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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.
Cheryl L Ackert-Bicknell, PhD principal investigator
University of Colorado, Denver
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 Age-Related Osteoporosis, run by University of Colorado, Denver 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 2 inclusion and 12 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 3 Apr 2024. 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?
Contact Cheryl L Ackert-Bicknell, PhD (3037246623, CHERYL.ACKERT-BICKNELL@CUANSCHUTZ.EDU), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gene and transcript quantification (time frame: Baseline). 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?
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 3 Apr 2024.