The Antibiotic Rifampin to Reduce High Levels of Blood and Urine Calcium in IIH

August 30, 2021 updated by: Etienne Sochett, The Hospital for Sick Children

Rifampin to Reduce Elevated Levels of Blood and Urine Calcium in Patients With Idiopathic Infantile Hypercalcemia

Idiopathic infantile hypercalcemia(IIH) is a rare,genetic disorder of mineral metabolism. Biallelic loss of functions 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 suggest rifampin as an investigational drug to induce over-expression of CYP3A4, an important enzyme that provides an alternate catabolic pathway for inactivation of vitamin D metabolites. In this study, investigators will recruit 5 patients with biallelic inactivating mutations of CYP24A1. Participants will be followed prospectively for a total 6-11 months. This will include 2 months of observation, 2 months of receiving the starting dose of rifampin, followed by 2 month washout phase. Efficacy of the starting dose of rifampin will be determined prior to proceeding only in non responders to the escalation dose of rifampin 10mg/kg/day.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Idiopathic infantile hypercalcemia(IIH) is a rare,genetic disorder of mineral metabolism characterized by severe hypercalcemia and/or hypercalciuria, suppressed serum levels of parathyroid hormone (PTH), elevated levels of the active vitamin D metabolite, 1,25(OH)2D, and nephrocalcinosis. Biallelic loss of functions 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 suggest rifampin as an investigational drug to induce over-expression of CYP3A4, an important P450 microsomal 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 results and support for an open label, escalating dose study to assess the effect, safety, and tolerability of once daily oral rifampin for two months in participants with IIH due to inactivating mutations in CYP24A1.

In this study, Investigators will recruit 5 patients with biallelic inactivating mutations of CYP24A1. Participants will be followed prospectively for a total 6-11 months. This will include 2 months of observation, 2 months of receiving the starting dose of rifampin, followed by 2 month washout phase. Efficacy of the starting dose of rifampin will be determined prior to proceeding only in non responders to the escalation dose of rifampin 10mg/kg/day. In addition to determining if this treatment is efficacious in reducing elevated serum and urinary calcium in patients, it will be determined if there is a dose effect of rifampin. As well, detailed measurements of vitamin D metabolites will determine if rifampin reduces hypercalcemia through increased CYP3A4 activity.

Study Type

Interventional

Enrollment (Anticipated)

5

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Recruiting
        • The Hospital for Sick Children
        • Contact:
        • Contact:
        • Principal Investigator:
          • Etienne Sochett, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • all patients between 6 months- 17 years of age with the clinical phenotype of idiopathic infantile hypercalcemia
  • Biochemical evidence of this disorder: Serum calcium>upper limit of the reference age for range; high, 1,25 (OH)D; reduced PTH, reduced 24,25(OH)2D, and suppresses 24,1,25 (OH)2D, normal serum creatinine, AST, and ALT with or without
  • biallelic inactivating mutations of CYP24A1
  • mutations in newly published genes which are shown during the course of the study to cause an inappropriate increase in 1,25 (OH)2D

Exclusion Criteria:

  • Allergy to rifampin or related medications
  • Pregnancy or breastfeeding
  • Significant cardiac, hepatic, or endocrine comorbidities
  • Taking any medications/foods known to interact with CYP3A4 or 1,25 (OH)D
  • Parents or guardians or subjects who in the opinion of the Investigator may be non compliant with study schedules or procedures
  • Other comorbidities considered unsuitable by the investigator, including TB

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rifampin
All subjects
Drug: Rifampin 150 mg, 300 mg capsules and 25 mg/mL oral suspension
Starting Dose (V2): 5 mg/kg/day (max 600mg/day) orally for 2 months followed by a 2 month washout period V4: After washout period, only Non-responders will escalate dose to 10 mg/kg/day (max 600mg/day) orally for 2 months
Other Names:
  • Rifadin, Rofact, Rifampicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Serum Calcium
Time Frame: 40 weeks
Measured at baseline and every 2 months (8 weeks)
40 weeks
Change in Serum Parathyroid Hormone
Time Frame: 40 weeks
measured at baseline and every 2 months ( 8 weeks)
40 weeks
Change in Urinary calcium excretion
Time Frame: 40 weeks
Measured at baseline and every 2 months( 8 weeks)
40 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Nephrocalcinosis
Time Frame: 40 weeks
Renal ultrasound performed before and after treatment
40 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Hospital for Sick Children

Collaborators

Children's Hospital of Philadelphia
Canadian Institutes of Health Research (CIHR)
Cures Within Reach

Investigators

  • Principal Investigator: Etienne Sochett, MD, The Hospital for Sick Children

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 22, 2018

Primary Completion (Anticipated)

December 31, 2021

Study Completion (Anticipated)

December 31, 2021

Study Registration Dates

First Submitted

December 13, 2017

First Submitted That Met QC Criteria

December 22, 2017

First Posted (Actual)

December 27, 2017

Study Record Updates

Last Update Posted (Actual)

August 31, 2021

Last Update Submitted That Met QC Criteria

August 30, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1000057141

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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