The Antibiotic Rifampin to Reduce High Levels of Blood and Urine Calcium in IIH
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|ClinicalTrials.gov Identifier: NCT03384121|
Recruitment Status : Unknown
Verified December 2017 by Etienne Sochett, The Hospital for Sick Children.
Recruitment status was: Recruiting
First Posted : December 27, 2017
Last Update Posted : December 27, 2017
|Condition or disease||Intervention/treatment||Phase|
|Idiopathic Infantile Hypercalcemia - Mild Form||Drug: Rifampin 150 mg, 300 mg capsules and 25 mg/mL oral suspension||Phase 1|
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 (Clinical Trial)|
|Estimated Enrollment :||5 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||This is a phase 1 pilot study whereby all participants start the study at a starting dose 5mg/kg/day (at study visit 2) for two months, and those that do not respond to 5mg/kg/day, otherwise known as non-responders, will receive a higher dose of 10 mg/kg/day (at study visit 4) for another two months. Recruited patients will be followed prospectively for a total of 6-11 months. This will include 2 months of observation, 2 months of receiving the starting dose of rifampin of 5mg/kg/day with a maximum dose of 600mg/day followed by a 2 month washout phase. The efficacy of the starting dose of rifampin will be determined prior to proceeding only in non-responders to the higher dose of 10 mg/kg/day with a maximum dose of 600 mg/day.|
|Masking:||None (Open Label)|
|Official Title:||Rifampin to Reduce Elevated Levels of Blood and Urine Calcium in Patients With Idiopathic Infantile Hypercalcemia|
|Estimated Study Start Date :||December 2017|
|Estimated Primary Completion Date :||June 30, 2019|
|Estimated Study Completion Date :||June 30, 2019|
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 Name: Rifadin, Rofact, Rifampicin
- Change in Serum Calcium [ Time Frame: 40 weeks ]Measured at baseline and every 2 months (8 weeks)
- Change in Serum Parathyroid Hormone [ Time Frame: 40 weeks ]measured at baseline and every 2 months ( 8 weeks)
- Change in Urinary calcium excretion [ Time Frame: 40 weeks ]Measured at baseline and every 2 months( 8 weeks)
- Nephrocalcinosis [ Time Frame: 40 weeks ]Renal ultrasound performed before and after treatment
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): NCT03384121
|Contact: Yesmino Elia, MSc||416-813-7654 ext firstname.lastname@example.org|
|Contact: Michelle Furman, BMSc||416-813-7654 ext email@example.com|
|The Hospital for Sick Children||Recruiting|
|Toronto, Ontario, Canada, M5G 1X8|
|Contact: Etienne Sochett, MD 416-813-6218 firstname.lastname@example.org|
|Contact: Yesmino Elia, Msc. 416-813-7654 ext 1518 email@example.com|
|Principal Investigator: Etienne Sochett, MD|
|Principal Investigator:||Etienne Sochett, MD||The Hospital for Sick Children|