Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Rifampin in CYP24A1-related Hypercalcemia and Hypercalciuria (RICHH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03301038
Recruitment Status : Recruiting
First Posted : October 4, 2017
Last Update Posted : June 11, 2019
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Children's Hospital of Philadelphia

Brief Summary:
This study evaluates the efficacy of rifampin in the treatment of hypercalcemia and/or hypercalciuria in participants with biallelic inactivating mutations of the CYP24A1 gene. Eligible subjects will receive rifampin for a total of 16 weeks during this study.

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

Detailed Description:

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

Drug Information available for: Rifampin

Arm Intervention/treatment
Experimental: All Subjects Drug: Rifampin
Rifampin 5 mg/kg (max 300 mg) daily for 8 weeks, followed by rifampin 10 mg/kg (max 600 mg) daily for 8 weeks.
Other Names:
  • Rifadin
  • Rifampicin




Primary Outcome Measures :
  1. Serum albumin-adjusted calcium [ Time Frame: up to 32 weeks ]
    Measured at baseline and every 4 weeks

  2. Serum parathyroid hormone [ Time Frame: up to 32 weeks ]
    Measured at baseline and every 4 weeks

  3. Urinary calcium excretion [ Time Frame: up to 32 weeks ]
    Measured at baseline and every 4 weeks


Secondary Outcome Measures :
  1. Intestinal calcium absorption [ Time Frame: 8, 16 and 24 weeks post-dose ]
    Measured using stable calcium isotopes three times during the study

  2. Nephrocalcinosis [ Time Frame: Baseline and week 32 ]
    Renal ultrasound performed before and after treatment

  3. Rifampin pharmacokinetics [ Time Frame: 8, 16 and 24 weeks post-dose ]
    Measured three times during the study



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   6 Months to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males or females age 6 months to 50 years.
  • Biallelic mutations of CYP24A1
  • Serum and/or urinary calcium above the normal reference range for age
  • Serum PTH concentration <20 pg/ml
  • Elevated or normal serum concentration of 1,25-dihydroxyvitamin D3.

Exclusion Criteria:

  • Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
  • Allergy to rifampin or related medications
  • Current therapies with medications or foods that are considered by the research team to potentially affect mineral metabolism, alter clearance of rifampin, or inhibit CYP3A4.
  • Pregnancy or breastfeeding
  • Laboratory abnormalities that indicate clinically significant hepatic, or renal disease:

AST/SGOT > 2.0 times the upper limit of normal ALT/SGPT > 2.0 times the upper limit of normal Total bilirubin > 2.0 times the upper limit of normal Creatinine > 2.0 times the upper limit of normal


Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Michael A Levine, MD 267-426-3907 levinem@chop.edu
Contact: Colin P Hawkes, MD 215-590-3174 hawkesc@email.chop.edu

Locations
Layout table for location information
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Michael A Levine, MD    267-426-3907    levinem@chop.edu   
Contact: Colin P Hawkes, MD    215-590-3174    hawkesc@email.chop.edu   
Sub-Investigator: Colin P Hawkes, MD         
Principal Investigator: Michael A Levine, MD         
Sponsors and Collaborators
Children's Hospital of Philadelphia
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Layout table for investigator information
Principal Investigator: Michael A Levine, MD Children'sHospital of Philadelphia

Publications:
Layout table for additonal information
Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT03301038     History of Changes
Other Study ID Numbers: 16-013429
R01DK112955 ( U.S. NIH Grant/Contract )
First Posted: October 4, 2017    Key Record Dates
Last Update Posted: June 11, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Children's Hospital of Philadelphia:
hypercalcemia
nephrocalcinosis
CYP24A1
hypercalciuria
Additional relevant MeSH terms:
Layout table for MeSH terms
Genetic Diseases, Inborn
Hypercalcemia
Hypercalciuria
Calcium Metabolism Disorders
Metabolic Diseases
Water-Electrolyte Imbalance
Urological Manifestations
Signs and Symptoms
Rifampin
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers