The Impact of Glomerular Disorders on Bone Quality and Strength

Bone Fracture Clinical Trial

— BoneGN  

Official title:

The Impact of Glomerular Disorders on Bone Quality and Strength

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04528446
• Other study ID #: AAAS0922
• Secondary ID: R01DK119266
• Status: Recruiting
• Start date: June 14, 2019
• Est. completion date: December 15, 2024

Study information

• Verified date: April 2022
• Source: Columbia University
• Contact: Maria A. Aponte
• Phone: (212) 342-4678
• Email: maa2308[@]cumc.columbia.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 270
• Est. completion date: December 15, 2024
• Est. primary completion date: December 15, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 5 Years to 55 Years

Eligibility

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

Inclusion Criteria for healthy reference participants

1. Males or females 5 to 55 years of age (premenopausal for women)

2. Females must have a negative urine/serum pregnancy test

3. 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.

Related Conditions & MeSH terms

• Bone Diseases
• Bone Diseases, Metabolic
• Bone Fracture
• Fractures, Bone
• Glomerular Disease
• Metabolic Diseases

Intervention

Radiation:
• Dual-energy X-ray absorptiometry
DXA whole body, hip, spine, and radius at baseline, and 12-month visit.
• High Resolution Peripheral Quantitative Computed Tomography (HR-pQCT)
HR-pQCT of the radius and tibia at baseline, and 12-month visit.

Other:
• Blood draw and Urine collection
The blood draw can be completed +/- 3 weeks from baseline or 12-month visit.
• Questionnaires
Questionnaires regarding fracture history, physical activity and dietary intake at baseline, and 12-month visit.

Locations

Country	Name	City	State
United States	Columbia University Irving Medical Center	New York	New York
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Columbia University	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (7)

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. Review. Erratum in: Am J Kidney Dis. 2017 May;69(5):712. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline and 12 months
Primary	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.	Baseline and 12 months
Secondary	Radius mid-shaft failure load	Measured with HR-pQCT	Up to 12 months
Secondary	Tibia mid-shaft failure load	Measured with HR-pQCT	Up to 12 months
Secondary	Cortical density of radius	Measured with HR-pQCT	Up to 12 months
Secondary	Cortical density of tibia	Measured with HR-pQCT	Up to 12 months
Secondary	Cortical thickness of radius	Measured with HR-pQCT	Up to 12 months
Secondary	Cortical thickness of tibia	Measured with HR-pQCT	Up to 12 months
Secondary	Areal bone mineral density (aBMD) at the hip	Hip (total and femoral neck) is measured with dual-energy x-ray absorptiometry (DXA)	Up to 12 months
Secondary	aBMD at forearm	Forearm (one-third and ultradistal radius) is measured with DXA	Up to 12 months
Secondary	aBMD at lumbar spine	Lumbar spine is measured with DXA	Up to 12 months
Secondary	Bone mineral content at the hip	Hip (total and femoral neck) is measured with dual-energy x-ray absorptiometry (DXA)	Up to 12 months
Secondary	Bone mineral content at forearm	Forearm (one-third and ultradistal radius) is measured with DXA	Up to 12 months
Secondary	Bone mineral content at lumbar spine	Lumbar spine is measured with DXA	Up to 12 months