Pathogenesis of Compromised Bone Quality and Mechanics in Chronic Kidney Disease

Pathogenesis of Compromised Bone Quality and Mechanics in Chronic Kidney Disease



Sponsors


Source

Columbia University

Oversight Info

Has Dmc

Yes

Is Fda Regulated Drug

No

Is Fda Regulated Device

No


Brief 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. 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).

Overall Status

Recruiting

Start Date

2016-07-01

Completion Date

2020-06-30

Primary Completion Date

2019-03-01

Study Type

Observational

Primary Outcome

Measure

Time Frame

Determine amounts of abnormal collagen present in the bone of CKD patients
2.5 years
Determine if greater amounts of abnormal collagen in the bone of CKD patients decreases bone strength
1 year
To identify non-invasive biomarkers of advanced glycation end-products in bone collagen
1 year

Number Of Groups

1

Enrollment

36

Conditions


Intervention

Intervention Type

Other

Intervention Name


Description

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.

Arm Group Label

Kidney disease


Eligibility

Study Pop

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.

Sampling Method

Non-Probability Sample

Criteria

Inclusion Criteria:

- Chronic kidney disease stage 3, 4 or 5

- Stable dose of vitamin D for 2-months

Exclusion Criteria:

- 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).

- 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

Gender

All

Minimum Age

40 Years

Maximum Age

N/A

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Thomas Nickolas, MD,MS
Principal Investigator
Columbia University

Overall Contact

Last Name

Thomas Nickolas, MD, MS

Phone

212-305-5020

Email



Location

Facility

Status

Contact

Columbia/CUMC
New York New York 10032 United States
Recruiting
Last Name: Principal Investigator
Phone: 212-305-5020
Email: [email protected]

Location Countries

Country

United States


Verification Date

2018-08-01

Lastchanged Date

N/A

Firstreceived Date

N/A

Responsible Party

Responsible Party Type

Principal Investigator

Investigator Affiliation

Columbia University

Investigator Full Name

Thomas Nickolas, MD MS

Investigator Title

Associate Professor of Medicine


Keywords


Has Expanded Access

No

Condition Browse


Secondary Id

1R01DK110871-01

Arm Group

Arm Group Label

Kidney disease

Description

Patients who participate in our study are 40 years old or older and have a Chronic kidney disease stage 3, 4 or 5.


Firstreceived Results Date

N/A

Overall Contact Backup

Last Name

Maria Alejandra Aponte

Phone

212-342-4678

Email



Biospec Retention

Samples With DNA

Biospec Descr

We would like to store the biological samples that you agreed to provide as part of this
study: Blood, bone, urine and muscle.

DNA taken from these samples and/or the data obtained from the study and possibly use them
for future research. They will be stored at CUMC either with the researchers on this study or
in a central storage facility called a repository.

Patient Data

Sharing Ipd

Undecided


Firstreceived Results Disposition Date

N/A

Study Design Info

Observational Model

Cohort

Time Perspective

Cross-Sectional


Study First Submitted

August 8, 2018

Study First Submitted Qc

August 8, 2018

Study First Posted

August 10, 2018

Last Update Submitted

August 9, 2018

Last Update Submitted Qc

August 9, 2018

Last Update Posted

August 13, 2018


ClinicalTrials.gov processed this data on August 13, 2018

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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