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RecruitingNCT04528446BoneGNUpdated Jul 1, 2024

The Impact of Glomerular Disorders on Bone Quality and Strength

An observational study in Glomerular Disease, Bone Diseases, Metabolic and Bone Fracture, sponsored by Columbia University. Recruiting at 2 sites in United States. Open to participants aged 5 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-07-01.

Sponsored by Columbia University · Observational

Study type
Observational
Model
Case-control
Time perspective
Prospective
Enrollment
270
Ages
5 Years to 55 Years
Sex
All
01

Study summary

The primary objectives of this study are to: (1) determine the impact of glomerular disease on bone strength and (2) investigate the pathophysiologic underpinnings of impaired bone strength in glomerular disease.

Read the detailed description

Children and adults with glomerular disease have unique and potentially modifiable risk factors for compromised bone health, but our current understanding of skeletal fragility in glomerular disease is lacking. In the first large population-based cohort study, we recently found that primary glomerular disease was independently associated with an increased risk of incident fracture, and that hip fracture risk was >2-fold greater in patients younger vs. older than 40 years of age. Mechanisms that drive increased fracture risk in glomerular disease are not clear but likely multifactorial. Our prior work demonstrated that glomerular disease is associated with disturbances in vitamin D and mineral metabolism, in addition to and exacerbated by reduced kidney function.

Patients with glomerular disease are also exposed to medications which may negatively impact bone health, most notably high-dose and long-term glucocorticoid therapy. Identifying modifiable factors that compromise bone strength will facilitate the development of strategies to reduce fractures and other skeletal complications across the life course. The proposed multi-center study will leverage the infrastructure of the NIH-funded Cure Glomerulopathy (CureGN) prospective cohort study and the resources of two health systems with expertise in state-of-the-art high-resolution bone imaging methods, to conduct the first prospective, longitudinal study to assess determinants of impaired bone quality and strength in glomerular disease.

02

Conditions studied

  • Glomerular Disease
  • Bone Diseases, Metabolic
  • Bone Fracture

Keywords

  • Kidney Disease
  • Bone Fracture
03

Who can participate

Ages eligible
5 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

Prospective cohort study of 150 CureGN participants (100 adults/50 children) will be evaluated at baseline and 12 months.

The CureGN DCC at Arbor Research will identify CureGN participants eligible for inclusion. Recruitment of healthy participants will also occur by leveraging the services of the CHOP Recruitment Enhancement Core (REC), Pediatric Research Consortium (PeRC) and the RecruitMe tool provided by the Clinical Trials Office at CUMC. Healthy adult controls will be recruited from patients who receive outpatient care within the Penn Primary Care Networks, Penn employees and students, an extensive database of individuals who have participated in prior research studies at Penn and through local advertising on the Penn campus.

Eligibility criteria

Inclusion Criteria for participants with glomerular disease:

  1. CureGN participant or CureGN Eligible

    CureGN eligible is defined as having a diagnosis of Glomerulonephropathy (GN). Patients would otherwise be enrolled in be in CureGN study, except for lacking a minor entry criteria, such as:

    1. First diagnostic kidney biopsy within 5 years of CureGN study enrollment
    2. Access to first kidney biopsy report and/or slides or not being interested in study participation.
  2. Males or females 5 to 55 years (premenopausal for women)
  3. Females must have a negative urine/serum pregnancy test
  4. Stable doses of nutritional vitamin D or active vitamin D therapy for at least 3 months before enrollment ((if on either form of Vitamin D)
  5. Consent/Parental/guardian permission (informed consent) and if appropriate, child assent

Exclusion Criteria for all participants

  1. Chronic Dialysis
  2. Solid organ transplantation
  3. Lower extremity amputations or non-ambulatory
  4. Malignancy requiring chemotherapy or metastatic to bone
  5. Metabolic bone disease (e.g., Paget's disease, primary hyperparathyroidism)
  6. Endocrinopathy (current hyperthyroidism or untreated hypothyroidism, Cushing's syndrome)
  7. Medical diseases (end stage liver disease, heart or lung disease, intestinal malabsorption)
  8. Those treated with bisphosphonates, teriparatide, calcitonin, selective estrogen receptor modulators, estrogen, or phenytoin in the past 12 months
  9. Previous bilateral wrist and tibia fractures
  10. Pregnant or lactating females
  11. Parents/guardians or participants who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
04

Study design

Observational model
Case-control
Time perspective
Prospective
Enrollment
270 participants (estimated)
Patient registry
No
Biospecimen retention
Samples without dna

Groups and cohorts

  • BoneGN participants

    Participants who have already been recruited into the CureGN study, or meet its criteria.

    Radiation: Dual-energy X-ray absorptiometry · Radiation: High Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) · Other: Blood draw and Urine collection · Other: Questionnaires

Interventions

  • RadiationDual-energy X-ray absorptiometry

    DXA whole body, hip, spine, and radius at baseline, and 12-month visit.

    Also known as: Bone density

  • RadiationHigh Resolution Peripheral Quantitative Computed Tomography (HR-pQCT)

    HR-pQCT of the radius and tibia at baseline, and 12-month visit.

    Also known as: HR-pQCT

  • OtherBlood draw and Urine collection

    The blood draw can be completed +/- 3 weeks from baseline or 12-month visit.

  • OtherQuestionnaires

    Questionnaires regarding fracture history, physical activity and dietary intake at baseline, and 12-month visit.

05

What researchers measure

Primary outcomes

  1. Change in radius bone strength (failure load)

    HR-pQCT will be used to assess bone microarchitecture and generate micro-finite element analysis (µFEA)-based estimates of bone strength.

    Time frame: Baseline and 12 months

  2. Change in tibia bone strength (failure load)

    HR-pQCT will be used to assess bone microarchitecture and generate micro-finite element analysis (µFEA)-based estimates of bone strength.

    Time frame: Baseline and 12 months

Secondary outcomes

  1. Radius mid-shaft failure load

    Measured with HR-pQCT

    Time frame: Up to 12 months

  2. Tibia mid-shaft failure load

    Measured with HR-pQCT

    Time frame: Up to 12 months

  3. Cortical density of radius

    Measured with HR-pQCT

    Time frame: Up to 12 months

  4. Cortical density of tibia

    Measured with HR-pQCT

    Time frame: Up to 12 months

  5. Cortical thickness of radius

    Measured with HR-pQCT

    Time frame: Up to 12 months

  6. Cortical thickness of tibia

    Measured with HR-pQCT

    Time frame: Up to 12 months

  7. Areal bone mineral density (aBMD) at the hip

    Hip (total and femoral neck) is measured with dual-energy x-ray absorptiometry (DXA)

    Time frame: Up to 12 months

  8. aBMD at forearm

    Forearm (one-third and ultradistal radius) is measured with DXA

    Time frame: Up to 12 months

  9. aBMD at lumbar spine

    Lumbar spine is measured with DXA

    Time frame: Up to 12 months

  10. Bone mineral content at the hip

    Hip (total and femoral neck) is measured with dual-energy x-ray absorptiometry (DXA)

    Time frame: Up to 12 months

  11. Bone mineral content at forearm

    Forearm (one-third and ultradistal radius) is measured with DXA

    Time frame: Up to 12 months

  12. Bone mineral content at lumbar spine

    Lumbar spine is measured with DXA

    Time frame: Up to 12 months

06

Study locations

2 of 2 sites recruiting
  • Columbia University Irving Medical Center
    New York, New York 10032, United States
    Recruiting
  • The Children's Hospital of Philadelphia
    Philadelphia, Pennsylvania 19104, United States
    • Erin Doherty · Contact · dohertye@email.chop.edu · 267-600-6233
    • Michelle R. Denburg, MD · Principal investigator
    Recruiting
07

References and documents

Publications

  • Webster AC, Nagler EV, Morton RL, Masson P. Chronic Kidney Disease. Lancet. 2017 Mar 25;389(10075):1238-1252. doi: 10.1016/S0140-6736(16)32064-5. Epub 2016 Nov 23. PubMed 27887750 ↗
  • Floege J, Amann K. Primary glomerulonephritides. Lancet. 2016 May 14;387(10032):2036-48. doi: 10.1016/S0140-6736(16)00272-5. Epub 2016 Feb 25. PubMed 26921911 ↗
  • Saran R, Robinson B, Abbott KC, Agodoa LY, Albertus P, Ayanian J, Balkrishnan R, Bragg-Gresham J, Cao J, Chen JL, Cope E, Dharmarajan S, Dietrich X, Eckard A, Eggers PW, Gaber C, Gillen D, Gipson D, Gu H, Hailpern SM, Hall YN, Han Y, He K, Hebert H, Helmuth M, Herman W, Heung M, Hutton D, Jacobsen SJ, Ji N, Jin Y, Kalantar-Zadeh K, Kapke A, Katz R, Kovesdy CP, Kurtz V, Lavalee D, Li Y, Lu Y, McCullough K, Molnar MZ, Montez-Rath M, Morgenstern H, Mu Q, Mukhopadhyay P, Nallamothu B, Nguyen DV, Norris KC, O'Hare AM, Obi Y, Pearson J, Pisoni R, Plattner B, Port FK, Potukuchi P, Rao P, Ratkowiak K, Ravel V, Ray D, Rhee CM, Schaubel DE, Selewski DT, Shaw S, Shi J, Shieu M, Sim JJ, Song P, Soohoo M, Steffick D, Streja E, Tamura MK, Tentori F, Tilea A, Tong L, Turf M, Wang D, Wang M, Woodside K, Wyncott A, Xin X, Zang W, Zepel L, Zhang S, Zho H, Hirth RA, Shahinian V. US Renal Data System 2016 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis. 2017 Mar;69(3 Suppl 1):A7-A8. doi: 10.1053/j.ajkd.2016.12.004. No abstract available. Erratum In: Am J Kidney Dis. 2017 May;69(5):712. doi: 10.1053/j.ajkd.2017.03.001. PubMed 28236831 ↗
  • Clark SL, Denburg MR, Furth SL. Physical activity and screen time in adolescents in the chronic kidney disease in children (CKiD) cohort. Pediatr Nephrol. 2016 May;31(5):801-8. doi: 10.1007/s00467-015-3287-z. Epub 2015 Dec 18. PubMed 26684326 ↗
  • Denburg MR, Kumar J, Jemielita T, Brooks ER, Skversky A, Portale AA, Salusky IB, Warady BA, Furth SL, Leonard MB. Fracture Burden and Risk Factors in Childhood CKD: Results from the CKiD Cohort Study. J Am Soc Nephrol. 2016 Feb;27(2):543-50. doi: 10.1681/ASN.2015020152. Epub 2015 Jul 2. PubMed 26139439 ↗
  • Phan V, Blydt-Hansen T, Feber J, Alos N, Arora S, Atkinson S, Bell L, Clarson C, Couch R, Cummings EA, Filler G, Grant RM, Grimmer J, Hebert D, Lentle B, Ma J, Matzinger M, Midgley J, Pinsk M, Rodd C, Shenouda N, Stein R, Stephure D, Taback S, Williams K, Rauch F, Siminoski K, Ward LM; Canadian STOPP Consortium. Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome. Osteoporos Int. 2014 Feb;25(2):627-37. doi: 10.1007/s00198-013-2466-7. Epub 2013 Aug 16. PubMed 23948876 ↗
  • Alem AM, Sherrard DJ, Gillen DL, Weiss NS, Beresford SA, Heckbert SR, Wong C, Stehman-Breen C. Increased risk of hip fracture among patients with end-stage renal disease. Kidney Int. 2000 Jul;58(1):396-9. doi: 10.1046/j.1523-1755.2000.00178.x. PubMed 10886587 ↗

Individual participant data

Plan to share: No — Only investigators and study team members that have completed appropriate institutional review board (IRB) training/approval are eligible to collect and work on information collected from this study.

08

Registry details

Key details

Study ID
NCT04528446
Lead sponsor
Columbia University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Responsible party
Thomas Nickolas, MD MS (Professor of Medicine, Columbia University) — Principal investigator
First posted
Aug 27, 2020
Start date
Jun 14, 2019
Primary completion
Dec 2024 (estimated)
Completion
Dec 2024 (estimated)
Last update
Jul 1, 2024

Study contacts

Maria A. Aponte
Contact
maa2308@cumc.columbia.edu
(212) 342-4678
Thomas L. Nickolas, MD
Contact
tln2001@cumc.columbia.edu
(212) 305-3273
Thomas L. Nickolas, MD
principal investigator · Columbia University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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