Effectiveness of Paricalcitol in Reducing Parathyroid Hormone (PTH) Levels in X-linked Hypophosphatemic Rickets

NCT ID: NCT00417612

Last Updated: 2020-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2012-08-31

Brief Summary

The purpose of this study is to determine the effectiveness of paricalcitol, a form of synthetic vitamin D, in lowering parathyroid hormone (PTH) levels and reducing disease symptoms in children and adults with X-linked hypophosphatemic (XLH) rickets.

Detailed Description

XLH rickets is a rare inherited disorder in which the bones become painfully soft and bend easily because of a phosphate deficiency. This genetic defect causes the kidneys to allow excretion of an inappropriately high amount of phosphate into the urine. The kidneys are also unable to convert vitamin D into a form usable by the body, resulting in inadequate amounts of active vitamin D. Because vitamin D is needed to absorb calcium and phosphate from the intestine, this deficiency further reduces phosphate levels. Without the sufficient phosphate needed for normal bone growth, individuals with XLH rickets typically develop skeletal malformations, bone pain, and abnormally bowed legs. Hyperparathyroidism, a condition in which the parathyroid glands excrete excess amounts of PTH, also occurs frequently in individuals with XLH rickets, and may play a significant role in the skeletal complications associated with XLH rickets. The purpose of this study is to determine the effectiveness of paricalcitol in lowering PTH levels and reducing disease symptoms in individuals with XLH rickets.

This study will last 12 months. Participants will be randomly assigned to receive either paricalcitol or placebo, taken in the form of two pills daily for the duration of the study. During a baseline 3-day inpatient hospital stay, participants will undergo a physical exam, a cardiac ultrasound, a bone scan, blood collection, and a radiographic skeletal survey. The skeletal survey will include x-rays of various body parts. Participants who are 18 years or younger will not undergo the radiographic skeletal survey. Study visits for all participants will occur every 2 months until the end of the study. These visits will include a physical exam, review of disease symptoms, blood and urine collection, and a check of medication compliance.

Conditions

Hypophosphatemia, Familial; Hyperparathyroidism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Participants given active drug, paricalcitol (Zemplar), in effort to reduce PTH level

Group Type: EXPERIMENTAL

Paricalcitol

Intervention Type: DRUG

Paricalcitol given first as a dose of 2 capsules once per day. Dose titration as needed per biochemical results at outpatient visits.

2

Participants given placebo capsule to match for comparison

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo sugar pill

Interventions

Paricalcitol

Paricalcitol given first as a dose of 2 capsules once per day. Dose titration as needed per biochemical results at outpatient visits.

Intervention Type: DRUG

Placebo

Placebo sugar pill

Intervention Type: OTHER

Other Intervention Names

Zemplar

Eligibility Criteria

Inclusion Criteria

• Diagnosis of XLH rickets
• Fasting serum calcium of 10.7 mg/dl or less
• Fasting PTH greater than 40 nleq/ml and less than 120 nleq/ml in the mid-molecule PTH assay at screening (upper limit of normal is 25 nleq/ml)
• Willing and able to participate in the trial
• Taking stable dose of standard therapy for XLH rickets for at least 2 months prior to study entry

Exclusion Criteria

• Parent or guardian willing to provide informed consent, if applicable

• Concomitant kidney failure (estimated creatinine clearance less than 60 cc/min or serum creatinine greater than 1.5 mg/dl)
• Serum 25-hydroxy vitamin D less than 20 ng/ml. Participants meeting this criterion will receive vitamin D3 supplementation for 3 months and then be rescreened.
• Unable to comply with protocol and appropriate follow-up visits
• Treatment with agents that may affect skeletal metabolism, such as glucocorticoids and anticonvulsants

• Minimum Eligible Age: 9 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Thomas Carpenter

Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Thomas O. Carpenter, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale University School of Medicine

New Haven, Connecticut, United States

Countries

United States

References

Brown AJ, Dusso AS, Slatopolsky E. Vitamin D analogues for secondary hyperparathyroidism. Nephrol Dial Transplant. 2002;17 Suppl 10:10-9. doi: 10.1093/ndt/17.suppl_10.10.

Reference Type: BACKGROUND

PMID: 12386264 (View on PubMed)

McElduff A, Posen S. Parathyroid hormone sensitivity in familial X-linked hypophosphatemic rickets. J Clin Endocrinol Metab. 1989 Aug;69(2):386-9. doi: 10.1210/jcem-69-2-386.

Reference Type: BACKGROUND

PMID: 2753981 (View on PubMed)

Carpenter TO, Olear EA, Zhang JH, Ellis BK, Simpson CA, Cheng D, Gundberg CM, Insogna KL. Effect of paricalcitol on circulating parathyroid hormone in X-linked hypophosphatemia: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2014 Sep;99(9):3103-11. doi: 10.1210/jc.2014-2017. Epub 2014 Jul 16.

Reference Type: DERIVED

PMID: 25029424 (View on PubMed)

Other Identifiers

P50AR054086

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1P50AR054086-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

0607001636

Identifier Type: -

Identifier Source: org_study_id