Chronic Kidney DiseaseNCT03626246
Pathogenesis of Compromised Bone Quality and Mechanics in Chronic Kidney Disease
An observational study of Chronic Kidney Disease and End Stage Kidney Disease, run by Columbia University at 1 site in United States.
Trial summary
Kidney disease patients have a variety of bone disorders that result in bone loss and fractures. The mechanisms of these bone disorders are not clear but may be related to abnormal modification of a bone protein known as collagen. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Chronic Kidney Disease, End Stage Kidney Disease, Chronic Kidney Disease Mineral and Bone Disorder
- What is being tested?
- Kidney disease
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2016to 28 Feb 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
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 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Subjects will be recruited from the general nephrology clinics at Columbia University Medical Center. Subjects referred for both clinical biopsy and those only participating in the research protocol will be eligible. The main clinical indication for bone biopsy in CKD patients is to determine turnover status for selection of type of bone active agent.
Who may be able to join
- Chronic kidney disease stage 3, 4 or 5
- Stable dose of vitamin D for 2-months
Who cannot join
- Dialysis
- Current use or treatment in the past one year with oral or inhaled glucocorticoids for more than 90 days.
- Current use or treatment in the past one year with sex hormone/SERM therapy for more than 30 days.
- Any use of bisphosphonates.
- Use of anti-osteoporosis therapies (denosumab, teriparatide, calcitonin or anti-sclerostin antibodies) in last 2 years.
- Any solid organ transplant or bone marrow transplant (Not including skin or cornea).
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- Patients on non-aspirin anticoagulants that cannot be reasonably held for biopsy.
- Any cancers within 5-yrs of diagnosis that were metastatic to bone, and that are not in complete remission
- Any history of leukemia, multiple myeloma, lymphoma, amyloid or paraproteinemias.
- Any congenital or acquired collagen of bone diseases other than osteoporosis or renal osteodystrophy (Including but not limited to: Osteogenesis Imperfecta, X-Linked Hypophosphatemic Rickets, Pagets or Cushings Disease).
- History of Primary Hyperparathyroidism within 2-years of Parathyroidectomy.
- Hypoparathyroidism - primary or post-surgical
- Hyperthyroidism - if untreated and not on stable dose of medication for 6 months
- Hypothyroidism - if untreated and not on stable dose of medication for 6 months
- Non-ambulatory
- Bilateral lower extremity amputations.
- Weight >300 lbs.
- Medical disease - end stage heart, end stage liver, celiac disease and other intestinal malabsorption
Trial locations and contacts
1 site in 1 country.
About this study
Kidney disease patients have a variety of bone disorders that result in bone loss and fractures. The mechanisms of these bone disorders are not clear but may be related to abnormal modification of a bone protein known as collagen. Therefore, the investigators are conducting this research study to identify underlying mechanisms that are responsible for the disruption of bone collagen and determining whether the abnormal bone collagen impairs bone strength. The investigators intend to identify these mechanisms through studying relationships between kidney disease and bone strength via bone imaging, bone biopsy and non-invasive measures from blood and skin.
Read the detailed description
Kidney disease patients have abnormal protein (bone collagen) modifications in their bone that may increase the risk of breaking a bone (fracture). Preventing bone collagen from becoming abnormal may decrease the risk of breaking a bone, such as the spine or hip. Currently, the effect of abnormal bone collagen on bone strength is not fully defined, and there are no methods to measure the abnormal protein content without a bone biopsy. The purpose of this study is to define the effects of bone collagen on bone strength and to identify non-invasive markers that will tell us how much abnormal collagen is in the bone. If the investigators are able to identify a non-invasive marker of abnormal bone protein then they may be able to prevent the build-up of this protein and lower the risk of a fracture.
If the participant chooses to be in the study, the investigators will get information from the participant's medical records such as diagnosis, the medicines and treatments prescribed by the participant's doctor, and the participant's lab test results.
There will be two study visits, each lasting about 3 hours.
Visit 1: At the baseline visit, study procedures include:
- Completing medical history, physical activity level, and dietary questionnaires for calcium and vitamin D.
- Blood sample
- Bone Imaging will: dual energy X-ray absorptiometry (DXA) to measure bone mineral density, high-resolution peripheral quantitative computed tomography (HRpQCT) to measure bone quality, and back x-rays to assess for the presence of spine fractures.Females who are able to become pregnant will also provide a urine specimen for pregnancy testing. (A negative pregnancy test is required prior to bone imaging.)
- Measure levels of Advanced Glycation End products (AGEs) in the skin of the participant's forearm and also in the participant's bone by bone biopsy. Advance Glycation End products may play a role in the development of weakened bone due to chronic kidney disease.
Visit 2: The participant's second visit will occur within 6-months of enrollment. At this visit, the participant will undergo a bone and muscle biopsy at the hip area under conscious sedation and a localized pain numbing medicine. The bone biopsy provides detailed information about the quality of the participant's bone that cannot be obtained through other tests like x-rays or blood tests. The investigators will use the bone biopsy to determine the amount of abnormal protein in the participant's bone. The muscle biopsy informs about the health of the participant's muscle fibers and allows us to detect any muscle mass wasting associated to chronic kidney disease. Since the piece of muscle is taken form the bone biopsy, no extra incision is needed.
The duration of the participant's participation from start of antibiotics through the actual bone biopsy will be approximately 3 weeks and 5 days (26 days).
- Conditions
- Chronic Kidney Disease, End Stage Kidney Disease, Chronic Kidney Disease Mineral and Bone Disorder, Renal Osteodystrophy, Secondary Hyperparathyroidism
- Being tested
- Kidney disease
- Keywords
- Bone loss, Bone fracture, Bone biopsy, Kidney
- Medical subject headings
- Renal Insufficiency, Chronic, Kidney Failure, Chronic, Chronic Kidney Disease-Mineral and Bone Disorder, Hyperparathyroidism, Secondary, Bone Diseases, Metabolic, Fractures, Bone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Kidney diseaseOther
Being part of this study you agree to participate in all these interventions:
Genetic:
- Blood sample
Procedure/Surgery:
- Bone and muscle biopsies.
Radiation:
- Bone density (DXA)
- Thoracic and lumbar spine plain films.
- HRpQCT: high-resolution peripheral quantitative computed tomography
Other:
- Completing medical history, physical activity level, and dietary questionnaires for calcium and vitamin D.
- Measure levels of Advanced Glycation End products (AGEs) in the skin.
| Study group | Role | What they receive |
|---|---|---|
| Kidney disease | Patients who participate in our study are 40 years old or older and have a Chronic kidney disease stage 3, 4 or 5. Receives: Other: Kidney disease |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine amounts of abnormal collagen present in the bone of CKD patients
In patients with CKD stage 3-5, the investigators will obtain transiliac crest bone biopsies and determine the amount of advanced glycation end-products that are present in bone collagen
Measured: 2.5 years
Determine if greater amounts of abnormal collagen in the bone of CKD patients decreases bone strength
In patients with CKD stage 3-5, the investigators will perform biomechanical testing of bone biopsy specimens and determine if greater degree of advanced glycation end-product modification of bone collagen changes bone strength.
Measured: 1 year
To identify non-invasive biomarkers of advanced glycation end-products in bone collagen
In patients with CKD stage 3-5, to obtain blood and skeletal imaging with high resolution peripheral computed tomography and to determine if the concentration of advanced glycation end-products in bone collagen can be identified by non-invasive methods.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2018
- Study start1 Jul 2016
- Primary completion28 Feb 2020
- Study completion28 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Kidney DiseaseStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe 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
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Thomas Nickolas, MD MS, Columbia University
- Investigators
- Thomas Nickolas, MD,MS, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03626246
- Sponsor's protocol ID
- AAAQ7778
- Other IDs
- 1R01DK110871-01
- Status last verified
- Jul 2021
- First submitted
- 8 Aug 2018
- Last updated
- 13 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
- 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 13 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pathogenesis of Compromised Bone Quality and Mechanics in Chronic Kidney Disease
- ClinicalTrials.gov ID
- NCT03626246
- Acronym / sponsor ID
- AAAQ7778
- Conditions
- Chronic Kidney Disease, End Stage Kidney Disease, Chronic Kidney Disease Mineral and Bone Disorder, Renal Osteodystrophy, Secondary Hyperparathyroidism
- Keywords
- Bone loss, Bone fracture, Bone biopsy, Kidney
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 1 Jul 2016 (actual)
- Primary completion
- 28 Feb 2020 (actual)
- Study completion
- 28 Feb 2020 (actual)
- First posted
- 10 Aug 2018 (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.
Kidney disease patients have a variety of bone disorders that result in bone loss and fractures. The mechanisms of these bone disorders are not clear but may be related to abnormal modification of a bone protein known as collagen. Therefore, the investigators are conducting this research study to identify underlying mechanisms that are responsible for the disruption of bone collagen and determining whether the abnormal bone collagen impairs bone strength. The investigators intend to identify these mechanisms through studying relationships between kidney disease and bone strength via bone imaging, bone biopsy and non-invasive measures from blood and skin.
Detailed description
Kidney disease patients have abnormal protein (bone collagen) modifications in their bone that may increase the risk of breaking a bone (fracture). Preventing bone collagen from becoming abnormal may decrease the risk of breaking a bone, such as the spine or hip. Currently, the effect of abnormal bone collagen on bone strength is not fully defined, and there are no methods to measure the abnormal protein content without a bone biopsy. The purpose of this study is to define the effects of bone collagen on bone strength and to identify non-invasive markers that will tell us how much abnormal collagen is in the bone. If the investigators are able to identify a non-invasive marker of abnormal bone protein then they may be able to prevent the build-up of this protein and lower the risk of a fracture.
If the participant chooses to be in the study, the investigators will get information from the participant's medical records such as diagnosis, the medicines and treatments prescribed by the participant's doctor, and the participant's lab test results.
There will be two study visits, each lasting about 3 hours.
Visit 1: At the baseline visit, study procedures include:
- Completing medical history, physical activity level, and dietary questionnaires for calcium and vitamin D.
- Blood sample
- Bone Imaging will: dual energy X-ray absorptiometry (DXA) to measure bone mineral density, high-resolution peripheral quantitative computed tomography (HRpQCT) to measure bone quality, and back x-rays to assess for the presence of spine fractures.Females who are able to become pregnant will also provide a urine specimen for pregnancy testing. (A negative pregnancy test is required prior to bone imaging.)
- Measure levels of Advanced Glycation End products (AGEs) in the skin of the participant's forearm and also in the participant's bone by bone biopsy. Advance Glycation End products may play a role in the development of weakened bone due to chronic kidney disease.
Visit 2: The participant's second visit will occur within 6-months of enrollment. At this visit, the participant will undergo a bone and muscle biopsy at the hip area under conscious sedation and a localized pain numbing medicine. The bone biopsy provides detailed information about the quality of the participant's bone that cannot be obtained through other tests like x-rays or blood tests. The investigators will use the bone biopsy to determine the amount of abnormal protein in the participant's bone. The muscle biopsy informs about the health of the participant's muscle fibers and allows us to detect any muscle mass wasting associated to chronic kidney disease. Since the piece of muscle is taken form the bone biopsy, no extra incision is needed.
The duration of the participant's participation from start of antibiotics through the actual bone biopsy will be approximately 3 weeks and 5 days (26 days).
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Kidney disease | – | Other: Kidney diseasePatients who participate in our study are 40 years old or older and have a Chronic kidney disease stage 3, 4 or 5. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Subjects will be recruited from the general nephrology clinics at Columbia University Medical Center. Subjects referred for both clinical biopsy and those only participating in the research protocol will be eligible. The main clinical indication for bone biopsy in CKD patients is to determine turnover status for selection of type of bone active agent.
Key inclusion criteria (2 listed)
- Chronic kidney disease stage 3, 4 or 5
- Stable dose of vitamin D for 2-months
Key exclusion criteria (18 listed)
- Dialysis
- Current use or treatment in the past one year with oral or inhaled glucocorticoids for more than 90 days.
- Current use or treatment in the past one year with sex hormone/SERM therapy for more than 30 days.
- Any use of bisphosphonates.
- Use of anti-osteoporosis therapies (denosumab, teriparatide, calcitonin or anti-sclerostin antibodies) in last 2 years.
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 |
|---|---|---|
| Kidney diseaseBeing part of this study you agree to participate in all these interventions: Genetic: • Blood sample Procedure/Surgery: • Bone and muscle biopsies. Radiation: * Bone density (DXA) * Thoracic and lumbar spine plain films. * HRpQCT: high-resolution peripheral quantitative computed tomography Other: * Completing medical history, physical activity level, and dietary questionnaires for calcium and vitamin D. * Measure levels of Advanced Glycation End products (AGEs) in the skin. | Other | Kidney disease |
Primary outcome
Determine amounts of abnormal collagen present in the bone of CKD patients
Time frame: 2.5 years
In patients with CKD stage 3-5, the investigators will obtain transiliac crest bone biopsies and determine the amount of advanced glycation end-products that are present in bone collagen
Determine if greater amounts of abnormal collagen in the bone of CKD patients decreases bone strength
Time frame: 1 year
In patients with CKD stage 3-5, the investigators will perform biomechanical testing of bone biopsy specimens and determine if greater degree of advanced glycation end-product modification of bone collagen changes bone strength.
To identify non-invasive biomarkers of advanced glycation end-products in bone collagen
Time frame: 1 year
In patients with CKD stage 3-5, to obtain blood and skeletal imaging with high resolution peripheral computed tomography and to determine if the concentration of advanced glycation end-products in bone collagen can be identified by non-invasive methods.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2021.
- 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. This study is not recruiting at the moment.
Thomas Nickolas, MD,MS principal investigator
Columbia University
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 Chronic Kidney Disease and End Stage Kidney Disease, run by Columbia University 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 18 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: finished, as of the sponsor's last update on 13 Jul 2021. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine amounts of abnormal collagen present in the bone of CKD patients (time frame: 2.5 years). The study lists 3 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 13 Jul 2021.