Hypoparathyroidism Natural History (SHINE)

Advancing Product Development for Hypoparathyroidism: A Prospective Natural History Study of the Clinical Outcomes and Regulation of Disordered Mineral Metabolism

This is a prospective three year natural history study of adults with hypoparathyroidism. The goal is to monitor patients with hypoparathyroidism to define end-organ damage in the context of the disease.

Funding Source- FDA OOPD

Study Overview

• Status: Recruiting
• Conditions: Hypoparathyroidism

Detailed Description

The goal of this study is to prospectively collect data on the natural history of hypoparathyroidism (HPT). This will enable longitudinal data collection of complications in this disease, specifically defining the epidemiology of end-organ complications of HPT that are related to high calcification propensity. It will also determine relationships between calcification burden and end-organ disease severity and progression risk and assess the utility of traditional and novel biomarkers of mineral and bone metabolism on disease diagnosis and monitoring. These data will inform future investigations on the development, study, and implementation of HPT end-organ disease modifying strategies and impact clinical practice in hypoparathyroidism.The study objectives are to:

1. Build a prospective cohort of patients to study HPT-associated end-organ damage.
2. Determine end-organ physiologic consequences of HPT.
3. Elucidate determinants of HPT-associated end-organ damage.

• Study Type: Observational
• Enrollment (Estimated): 94

Contacts and Locations

• Study Contact: Name: Aiden Brossfield; Phone Number: 212-305-9489; Email: avb2141@cumc.columbia.edu
• Study Contact Backup: Name: Joana Gjeci; Phone Number: 212-342-0132; Email: jg4032@cumc.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center - Harkness Pavillion
      • Principal Investigator: Mishaela Rubin, MD
      • Contact: Aiden Brossfield; Phone Number: 212-305-9489; Email: avb2141@cumc.columbia.edu
      • Contact: Joana Gjeci; Phone Number: 212-342-0132; Email: jg4032@cumc.columbia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Male or female ≥18 years of age with all hypoparathyroidism sub-types.

Description

Inclusion Criteria:

• An understanding, ability and willingness to fully comply with study procedures and restrictions.
• Ability to voluntarily provide written, signed and dated informed consent as applicable to participate in the study.
• Male or female ≥18 years of age with HPT. All HPT sub-types are eligible, including surgical (HPT-S) and nonsurgical (HPT-NS) HPT: autoimmune, genetic (including but not limited to: DiGeorge syndrome, autoimmune polyendocrine syndrome type 1, hypoparathyroidism sensorineural deafness and renal disease syndrome, Kearns-Sayre syndrome, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes [MELAS] syndrome, mitochondrial trifunctional protein [MTP] deficiency syndrome, Kenny-Caffey syndrome, Sanjad-Sakati syndrome, autosomal dominant hypocalcemia), infiltrative (granulomatous), mineral deposition (copper, iron), metastatic, radiation and idiopathic HPT.
• Diagnosis of HPT established based on historic hypocalcemia in the setting of inappropriately low serum PTH levels on two occasions.
• All treatment regimens are permitted, including but not limited to conventional management with calcium (e.g. calcium citrate, calcium carbonate, etc), active vitamin D (calcitriol, alfacalcidol), parent vitamin D, magnesium, phosphate binders and thiazides. Use of PTH-like drugs are permitted.

Exclusion Criteria:

• Functional HPT
• Transient HPT
• Pseudohypoparathyroidism
• Pregnancy

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kidney function	blood test for changes in eGFR (in mL/min/1.73m^2)	baseline, 6, 12, 18, 24, 30, 36 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kidney calcification	Changes in kidney calcification and stones will be assessed by abdominal CT in an optional imaging sub group. Results will be assessed and reported by a clinician.	Baseline and 36 Months
Brain calcification	Changes in brain calcification will be assessed by head CT in an optional imaging sub-group. Results will be assessed and reported by a clinician.	Baseline and 36 Months
Vascular calcification	Changes in vascular calcification will be assessed by leg arterial calcifications on high resolution quantitative computed tomography in all, and aortic calcifications on abdominal CT and vertebral fracture assessment by DXA in optional imaging sub-group	Baseline and 36 Months
Bone mineral density	Changes in dual energy X-ray absorptiometry will be assessed in an optional imaging sub-group	Baseline and 36 Months
Bone microarchitecture and bone strength	Changes in high resolution peripheral quantitative computed tomography will be assessed	Baseline and 36 Months
Cardiac function	Changes in EKG will be assessed	Baseline and 36 Months
Transcriptomic signaling for calcification	Changes in microRNA will be assessed	Baseline and 36 Months
Biomarkers blood	Changes in complete metabolic panel to see changes with eGFR (including albumin-corrected serum calcium), PTH, phosphorus, magnesium, 25(OH)D, 25(OH)D2, TSH, FT4.	baseline, 6, 12, 18, 24, 30, 36 Months
Biomarkers urine	24 hour urine will be collected for changes in calcium, creatinine, total volume and protein	baseline, 6, 12, 18, 24, 30, 36 Months
Dietary Intake	Food frequency questionnaires will be administered to measure changes in calcium, phosphorus, vitamin D, and sodium intake	baseline, 12, 24 and 36 Months
Cognitive Function	Changes in cognitive function will be assessed by NIH Toolbox®; Letter Fluency by the Controlled Oral Word Association Test with the letters FAS; Sematic Fluency by Animal Fluency; List Learning and Memory by the Hopkins Verbal Learning Test; subjective cognitive function by FACT-Cog	baseline, 12, 24 and 36 Months
Neurologic Tests of Motor Function	Repeated Chair Stand (RCS) test will be administered to see how many times a patient can sit in and stand from a chair in 30 seconds and "Timed Up and Go" Test will measure how many seconds it takes for a patient to walk to assess changes in motor function	baseline, 12, 24 and 36 Months
Quality of Life Through Self-Reported Questionnaires	Quality of life will be assessed by SF-36, FACIT-IF (self-reported fatigue), PGI-S and PGI-I (patient global impression of severity and impact), Hospital Anxiety and Depression Scale (HADS) and the HPT Symptom Diary and changes will be tracked through visits	baseline, 12, 24 and 36 Months
Calcioprotein Maturation Time	Will be obtained through blood collection and measured in minutes and changes will be tracked through visits	Baseline and 36 months
Sclerostin	Will be obtained through blood collection and measured in pmol/L and changes will be tracked through visits	Baseline and 36 months
FGF23	Will be obtained through blood collection and measured in pg/mL and changes will be tracked through visits	Baseline and 36 months

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: FDA Office of Orphan Products Development

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: December 23, 2022
• First Submitted That Met QC Criteria: March 20, 2023
• First Posted (Actual): March 31, 2023

Study Record Updates

• Last Update Posted (Actual): May 21, 2024
• Last Update Submitted That Met QC Criteria: May 19, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Parathyroid Diseases; Hypoparathyroidism
• Other Study ID Numbers: AAAU3302; R01FD007629 (U.S. FDA Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No