Suspected Deficient Activation of Vitamin D in Patients With Secondary Hyperparathyroidism (1hydroxylase)

Clinical and Molecular Characterization of Suspected Partial 25-hydroxyvitamin D-1-alpha-hydroxylase Deficiency

The purpose of this study is to determine if a reduction in the enzyme 1-hydroxylase, which activates Vitamin D, is the cause of overactivity of the parathyroid glands (called secondary hyperparathyroidism - normal blood calcium and elevated parathyroid hormone) in a selected group of young patients with normal kidney function.

Study Overview

• Status: Completed
• Conditions: Secondary Hyperparathyroidism
• Intervention / Treatment: Drug: Teriparatide

Detailed Description

Vitamin D, an essential nutrient, is produced by the skin after sunlight shines on it. Vitamin D must then be activated by both the liver and the kidneys to perform its function of maintaining strong bones and helping to prevent heart disease, infection, diabetes and cancer. Reduced kidney activation of Vitamin D occurs with advanced age and with all kidney diseases. We have identified a small group of patients who appear to have reduced ability of the kidneys to activate vitamin D, even though they are young and do not have chronic kidney disease. In these patients, we are comparing the ability of their kidneys to activate Vitamin D to that of healthy controls. To stimulate the kidneys to activate Vitamin D, we are giving parathyroid hormone intravenously over 8 hours and collecting blood and urine at baseline, 4 and 8 hours. This type of parathyroid infusion does not cause side effects. The gene that controls this activation is also being studied (by a simple blood test) to look for abnormalities. We are now actively recruiting healthy controls for this study.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland School of Medicine Division of Endocrinology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 59 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Caucasian female
• Age 40-59 years
• Serum creatinine < 1.3 and estimated glomerular filtration rate (GRF) > 60
• Serum calcium in the normal range (for U Md lab 8.6-10 mg/dl)
• Parathyroid hormone in the normal range (for U Md lab 12-54 pg/ml)
• Normal 25-hydroxyvitamin D level (30 ng/ml or higher)
• For women of childbearing age, non-pregnant (based on negative urine pregnancy test on the morning of the teriparatide infusion)

Exclusion Criteria:

• Non-caucasian
• Age under 40 and over 59 years
• Male
• Serum creatinine over 1.3 or estimated glomerular filtration rate (GFR) < 60
• Abnormal serum calcium (for U Md lab, below 8.6 or above 10 mg/dl)
• Abnormal parathyroid hormone (for U Md lab, above 65 or below 12 pg/ml)
• For women of childbearing age, non-pregnant (based on urine pregnancy test on the morning of the teriparatide infusion)
• History of bone radiation
• History of Paget disease of bone
• History of bone malignancy or metastases
• History of allergy or sensitivity to Forteo

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: teriparatide control; control subject	Drug: Teriparatide; Teriparatide will be given by continuous intravenous infusion at a rate of 12 pmol/kg/hr for 8 hours to both "patients" and "controls"; Other Names: Forteo
Experimental: Teriparatide Patient; Patient with secondary hyperparathyroidism	Drug: Teriparatide; Teriparatide will be given by continuous intravenous infusion at a rate of 12 pmol/kg/hr for 8 hours to both "patients" and "controls"; Other Names: Forteo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Level of Activated Vitamin D (1,25-dihydroxyvitamin D) After Parathyroid Hormone Infusion at Baseline, 4 and 8 Hours	1,25-D was measured at baseline, 4 and 8 hours after PTH infusion	baseline, 4 and 8 hours after start of infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Patients With Mutations in CYP27B1	CYP27B1 gene (the gene for 25-hydroxyvitamin D-1-alpha hydroxylase) was sequenced for all in patient group and compared with published control data	blood samples taken at baseline and sequenced over several days

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Investigators: Principal Investigator: Elizabeth A Streeten, MD, Division of Endocrinology, University of Maryland School of Medicine

Publications and helpful links

General Publications

• Streeten EA, Rogstad AS, Flammer KM, Zarbalian K, Ryan K, Horwitz M, Holick MF, Shelton J. Reduced parathyroid hormone-stimulated 1,25-dihydroxyvitamin d production in vitamin d sufficient postmenoposual women with low bone mass and idiopathic secondary hyperparathyroidism. Endocr Pract. 2013 Jan-Feb;19(1):91-9. doi: 10.4158/EP12151.OR.

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: September 17, 2008
• First Submitted That Met QC Criteria: September 17, 2008
• First Posted (Estimate): September 18, 2008

Study Record Updates

• Last Update Posted (Actual): April 1, 2022
• Last Update Submitted That Met QC Criteria: March 30, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: vitamin D; parathyroid; vitamin D deficiency; hyperparathyroidism
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Parathyroid Diseases; Neoplastic Processes; Hyperparathyroidism; Neoplasm Metastasis; Hyperparathyroidism, Secondary; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Teriparatide
• Other Study ID Numbers: H-28679 (Other Identifier: IRB number)