Clinical trial NCT04528446: The Impact of Glomerular Disorders on Bone Quality and Strength
Official title: The Impact of Glomerular Disorders on Bone Quality and Strength
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Glomerular Disease
Bone Diseases, Metabolic
Bone Fracture
Keywords: Kidney Disease
Bone Fracture
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2020-08-27
Enrollment: 270
Sex: ALL
Minimum age (years): 5
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

Brief 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.

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.

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.

Primary outcomes:
measure: Change in radius bone strength (failure load)
timeFrame: Baseline and 12 months
measure: Change in tibia bone strength (failure load)
timeFrame: Baseline and 12 months
Secondary outcomes:
measure: Radius mid-shaft failure load
timeFrame: Up to 12 months
measure: Tibia mid-shaft failure load
timeFrame: Up to 12 months
measure: Cortical density of radius
timeFrame: Up to 12 months
measure: Cortical density of tibia
timeFrame: Up to 12 months
measure: Cortical thickness of radius
timeFrame: Up to 12 months
measure: Cortical thickness of tibia
timeFrame: Up to 12 months
measure: Areal bone mineral density (aBMD) at the hip
timeFrame: Up to 12 months
measure: aBMD at forearm
timeFrame: Up to 12 months
measure: aBMD at lumbar spine
timeFrame: Up to 12 months
measure: Bone mineral content at the hip
timeFrame: Up to 12 months
measure: Bone mineral content at forearm
timeFrame: Up to 12 months
measure: Bone mineral content at lumbar spine
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Columbia University
name: Thomas L. Nickolas, MD
role: PRINCIPAL_INVESTIGATOR
References:
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