Rifampin in CYP24A1-related Hypercalcemia and Hypercalciuria (RICHH)
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|ClinicalTrials.gov Identifier: NCT03301038|
Recruitment Status : Recruiting
First Posted : October 4, 2017
Last Update Posted : June 11, 2019
|Condition or disease||Intervention/treatment||Phase|
|Idiopathic Infantile Hypercalcaemia - Severe Form Genetic Disease Hypercalcemia, Idiopathic, of Infancy Hypercalciuric Hypercalcemia Idiopathic Infantile Hypercalcemia - Mild Form Hypercalciuria||Drug: Rifampin||Phase 2|
Idiopathic infantile hypercalcemia (IIH; omim 143880) is a genetic disorder of mineral metabolism characterized by severe hypercalcemia and/or hypercalciuria, suppressed serum levels of parathyroid hormone (PTH) and elevated levels of the active vitamin D metabolite, 1,25(OH)2D. Biallelic inactivating mutations of CYP24A1, the gene encoding the 24-hydroxylase enzyme that represents the principal pathway for inactivation of vitamin D metabolites, cause the most common and severe form of IIH.
Investigators have preliminary data supporting a novel therapeutic approach to repurpose rifampin as an agent to induce over-expression of CYP3A4, an enzyme that is expressed in the liver and intestine. When CYP3A4 is induced, the increased enzyme activity provides an alternative catabolic pathway for inactivation of vitamin D metabolites. The purpose of this study is to obtain support for an open label, escalating dose study to assess the effect, safety, and tolerability of once daily oral rifampin in participants with IIH due to inactivating mutations in CYP24A1.
In this study, Investigators will recruit 18 patients with biallelic inactivating mutations of CYP24A1. Participants will be observed for 8-weeks before a 16-week treatment phase of rifampin and 8 further weeks of observation. In addition to following the effect of treatment on calcium homeostasis, Investigators will also study the pharmacokinetics of rifampin in this condition and the effect on intestinal calcium absorption.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Rifampin to Reduce Elevated Levels of Blood and Urine Calcium in Patients With Inactivating Mutations in the CYP24A1 Gene|
|Actual Study Start Date :||June 19, 2018|
|Estimated Primary Completion Date :||December 2023|
|Estimated Study Completion Date :||December 2030|
|Experimental: All Subjects||
Rifampin 5 mg/kg (max 300 mg) daily for 8 weeks, followed by rifampin 10 mg/kg (max 600 mg) daily for 8 weeks.
- Serum albumin-adjusted calcium [ Time Frame: up to 32 weeks ]Measured at baseline and every 4 weeks
- Serum parathyroid hormone [ Time Frame: up to 32 weeks ]Measured at baseline and every 4 weeks
- Urinary calcium excretion [ Time Frame: up to 32 weeks ]Measured at baseline and every 4 weeks
- Intestinal calcium absorption [ Time Frame: 8, 16 and 24 weeks post-dose ]Measured using stable calcium isotopes three times during the study
- Nephrocalcinosis [ Time Frame: Baseline and week 32 ]Renal ultrasound performed before and after treatment
- Rifampin pharmacokinetics [ Time Frame: 8, 16 and 24 weeks post-dose ]Measured three times during the study
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03301038
|Contact: Michael A Levine, MDfirstname.lastname@example.org|
|Contact: Colin P Hawkes, MDemail@example.com|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Michael A Levine, MD 267-426-3907 firstname.lastname@example.org|
|Contact: Colin P Hawkes, MD 215-590-3174 email@example.com|
|Sub-Investigator: Colin P Hawkes, MD|
|Principal Investigator: Michael A Levine, MD|
|Principal Investigator:||Michael A Levine, MD||Children'sHospital of Philadelphia|