The Impact of Glomerular Disorders on Bone Quality and Strength

NCT ID: NCT04528446

Last Updated: 2024-07-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

270 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-06-14

Study Completion Date

2024-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Glomerular Disease Bone Diseases, Metabolic Bone Fracture

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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BoneGN participants

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

Dual-energy X-ray absorptiometry

Intervention Type RADIATION

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

High Resolution Peripheral Quantitative Computed Tomography (HR-pQCT)

Intervention Type RADIATION

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

Blood draw and Urine collection

Intervention Type OTHER

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

Questionnaires

Intervention Type OTHER

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

Interventions

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Dual-energy X-ray absorptiometry

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

Intervention Type RADIATION

High Resolution Peripheral Quantitative Computed Tomography (HR-pQCT)

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

Intervention Type RADIATION

Blood draw and Urine collection

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

Intervention Type OTHER

Questionnaires

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

Intervention Type OTHER

Other Intervention Names

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Bone density HR-pQCT

Eligibility Criteria

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Inclusion Criteria

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

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.
Minimum Eligible Age

5 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role collaborator

Columbia University

OTHER

Sponsor Role lead

Responsible Party

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Thomas Nickolas, MD MS

Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Thomas L. Nickolas, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

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Columbia University Irving Medical Center

New York, New York, United States

Site Status RECRUITING

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Maria A. Aponte

Role: CONTACT

(212) 342-4678

Thomas L. Nickolas, MD

Role: CONTACT

(212) 305-3273

Facility Contacts

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Maria A. Aponte

Role: primary

212-342-4678

Erin Doherty

Role: primary

267-600-6233

References

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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.

Reference Type BACKGROUND
PMID: 27887750 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26921911 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28236831 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26684326 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26139439 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23948876 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10886587 (View on PubMed)

Other Identifiers

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R01DK119266

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AAAS0922

Identifier Type: -

Identifier Source: org_study_id

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