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

The Role of Parathyroid Hormone in the Pathogenesis of Skeletal Disease in X-linked Hypophosphatemic Rickets (XLH)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00417612

Enrollment

Registered

2007-01-01

Start date

2007-01-31

Completion date

2012-08-31

Last updated

2020-03-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hyperparathyroidism, Hypophosphatemia, Familial

Keywords

Rickets, Hypophosphatemia, Rickets, Vitamin D-Resistant, Rickets, X-linked hypophosphatemic

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.

Interventions

OTHERPlacebo

Placebo sugar pill

DRUGParicalcitol

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

9 Years to No maximum

Healthy volunteers

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 * Concomitant therapy for XLH rickets will not be an

Exclusion criteria

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

Design outcomes

Primary

Measure	Time frame	Description
Area Under the Curve for Parathyroid Hormone (PTHauc) Measurement	Measured at baseline and Month 12	Mean area under the curve for parathyroid hormone levels (PTHauc) sampled during a 26 hour study period, for Paricalcitol (Active Drug) and Placebo groups at Baseline and Month 12 .
Area Under the Curve for Parathyroid Hormone (PTH; Percentage Decrease)	Measured at baseline and Month 12	Mean PTHauc (% decrease) for Paricalcitol (Active Drug) and Placebo from Baseline to Month 12.
Reduction of Parathyroid Hormone Area Under the Curve (PTHauc) of 20% or Greater	Measured at baseline and Month 12	Clinically significant reduction of Mean PTHauc (% decrease \>/= 20) for Paricalcitol (Active Drug) and Placebo from Baseline to Month 12.

Secondary

Measure	Time frame	Description
Percent Change in Urinary Calcium Excretion From Baseline to 1 Year	Measured at baseline and Month 12	Percent change in daily urinary calcium excretion, which is calculated the measurements of the calcium in the subject's 24-hr urine collections done at baseline and at the 1 year timepoints
Static Parameters of Serum Alkaline Phosphatase at Baseline and 1 Year for Paricalcitol and Placebo Arms.	Measured at baseline and Month 12	—
Serum 1,25 (OH)2D	Measured at baseline and Month 12	—
Serum Intact Fibroblast Growth Factor 23 (FGF23)	Measured at baseline and Month 12	—
Serum Calcium	Measured at baseline and Month 12	—
Bone Scan Severity Score	Measured at baseline and Month 12	99-Tc-methylenediphosphonate bone scans were completed and analyzed using the following scale\: Bone scan severity scale with minimum score of 0 and maximum score of 4 (0 is no disease and 4 is greatest severity of disease). Appearance of lumbar spine and the sacroiliac region were used as internal references to which all suspected lesions were compared, and scored as follows: grade 0, normal scan without suspicious lesions grade 1, lesion(s) less intense than normal lumbar spine grade 2, lesion(s) similar in intensity to normal lumbar spine grade 3, lesions more intense than normal lumbar spine but similar to the normal sacroiliac region grade 4, lesions more intense than the normal sacroiliac region. \devised by nuclear medicine radiologist at Yale New Haven Hospital

Countries

United States

Participant flow

Participants by arm

Arm	Count
Paricalcitol (Active Drug) Participants given active drug, paricalcitol (Zemplar), in effort to reduce PTH level Paricalcitol: Paricalcitol given first as a dose of 2 capsules once per day. Dose titration as needed per biochemical results at outpatient visits.	22
Placebo Participants given placebo capsule to match for comparison Placebo: Placebo sugar pill	11
Total	33

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	2	0
Overall Study	Errant diagnosis	0	1
Overall Study	Lost to Follow-up	1	0
Overall Study	Protocol Violation	0	2

Baseline characteristics

Characteristic	Paricalcitol (Active Drug)	Placebo	Total
Age, Categorical <=18 years	2 Participants	1 Participants	3 Participants
Age, Categorical >=65 years	1 Participants	0 Participants	1 Participants
Age, Categorical Between 18 and 65 years	19 Participants	10 Participants	29 Participants
Region of Enrollment United States	22 participants	11 participants	33 participants
Sex: Female, Male Female	17 Participants	9 Participants	26 Participants
Sex: Female, Male Male	5 Participants	2 Participants	7 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	2 / 22	0 / 11
serious Total, serious adverse events	0 / 22	0 / 11

Outcome results

Primary

Area Under the Curve for Parathyroid Hormone (PTHauc) Measurement

Mean area under the curve for parathyroid hormone levels (PTHauc) sampled during a 26 hour study period, for Paricalcitol (Active Drug) and Placebo groups at Baseline and Month 12 .