Recruiting
Phase 1

Rifampin

Sponsor:

The Hospital for Sick Children

Code:

NCT03384121

Conditions

Idiopathic Infantile Hypercalcemia - Mild Form

Eligibility Criteria

Sex: All

Age: 0 - 17

Healthy Volunteers: Not accepted

Interventions

Rifampin 150 mg, 300 mg capsules and 25 mg/mL oral suspension

Study Details

Brief summary:

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.

Conditions

Idiopathic Infantile Hypercalcemia - Mild Form

Study ID

NCT03384121

Start date

Feb 22, 2018

Status verified date

Aug, 2021

Completion date

Dec 31, 2021

Anticipated

Primary completion date

Dec 31, 2021

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0 - 17

Healthy Volunteers: Not accepted

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 Design

Enrollment

5 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Rifampin

All subjects

Interventions

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

Primary outcome measure

  • Change in Serum Calcium [ Time Frame: 40 weeks ]
  • Change in Serum Parathyroid Hormone [ Time Frame: 40 weeks ]
  • Change in Urinary calcium excretion [ Time Frame: 40 weeks ]

Central Contacts and Locations

Central contacts

Locations

The Hospital for Sick Children

Recruiting

Toronto, Ontario, Canada, M5G 1X8

Contacts

Principal Investigator:

Etienne Sochett, MD

More Information

Sponsor

The Hospital for Sick Children

Last update posted

Aug 31, 2021

Last verified

Aug, 2021

Keywords

  • CYP24A1
  • Nephrocalcinosis
  • Hypercalcemia
  • Hypercalcuria

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by The Hospital for Sick Children on 2021-08-31.