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

• ClinicalTrials.gov Identifier: NCT00754442
• Recruitment Status: Completed
• First Posted: September 18, 2008
• Results First Posted: May 14, 2014
• Last Update Posted: November 4, 2019
• Sponsor: University of Maryland, Baltimore
• Information provided by (Responsible Party): Elizabeth Streeten, University of Maryland, College Park

Tracking Information

• First Submitted Date: September 17, 2008
• First Posted Date: September 18, 2008
• Results First Submitted Date: January 17, 2013
• Results First Posted Date: May 14, 2014
• Last Update Posted Date: November 4, 2019
• Study Start Date: February 2007
• Actual Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 13, 2014)

The Level of Activated Vitamin D (1,25-dihydroxyvitamin D) After Parathyroid Hormone Infusion at Baseline, 4 and 8 Hours [ Time Frame: baseline, 4 and 8 hours after start of infusion ]

1,25-D was measured at baseline, 4 and 8 hours after PTH infusion

• Original Primary Outcome Measures (submitted: September 17, 2008): The level of activated Vitamin D (1,25-dihydroxyvitamin D) after parathyroid hormone infusion [ Time Frame: 4 and 8 hours after start of infusion ]

Current Secondary Outcome Measures (submitted: May 13, 2014)

The Number of Patients With Mutations in CYP27B1 [ Time Frame: blood samples taken at baseline and sequenced over several days ]

CYP27B1 gene (the gene for 25-hydroxyvitamin D-1-alpha hydroxylase) was sequenced for all in patient group and compared with published control data

• Original Secondary Outcome Measures (submitted: September 17, 2008): Abnormalities in the gene for the 1-hydroxylase enzyme [ Time Frame: baseline ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Suspected Deficient Activation of Vitamin D in Patients With Secondary Hyperparathyroidism
• Official Title: Clinical and Molecular Characterization of Suspected Partial 25-hydroxyvitamin D-1-alpha-hydroxylase Deficiency
• Brief Summary: 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.
• 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
• Study Phase: Not Applicable
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic
• Condition: Secondary Hyperparathyroidism

Intervention

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 Name: Forteo

Study Arms

• Active Comparator: teriparatide control
  control subject
  Intervention: Drug: Teriparatide
• Experimental: Teriparatide Patient
  Patient with secondary hyperparathyroidism
  Intervention: Drug: Teriparatide

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 13, 2014): 20
• Original Estimated Enrollment (submitted: September 17, 2008): 16
• Actual Study Completion Date: August 2008
• Actual Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 40 Years to 59 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00754442
• Other Study ID Numbers: H-28679; H-28679 ( Other Identifier: IRB number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Elizabeth Streeten, University of Maryland, College Park
• Study Sponsor: University of Maryland, Baltimore
• Collaborators: Not Provided

Investigators

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

• PRS Account: University of Maryland, Baltimore
• Verification Date: August 2019