Rifampin for Genetic Disorders Related to High Calcium Levels

(RICHH Trial)

Overseen By Vashisht Arshanapally

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Hospital of Philadelphia

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Pregnancy, Breastfeeding, Hepatic disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 16 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This study evaluates the efficacy of rifampin in the treatment of hypercalcemia and/or hypercalciuria in participants with at least one inactivating mutation of the CYP24A1 gene. Eligible subjects will receive rifampin for a total of 16 weeks during this study.

Will I have to stop taking my current medications?

You may need to stop taking your current medications if they interact with rifampin, specifically if they affect certain liver enzymes (CYP3A4 or CYP3A5). It's best to discuss your current medications with the study team to see if they are compatible with the trial.

How does the drug Rifampin differ from other treatments for genetic disorders related to high calcium levels?

Rifampin is unique because it is primarily known as an antibiotic used to treat bacterial infections like tuberculosis, but it is being explored for its potential to modulate inflammation in genetic disorders related to high calcium levels. This is different from standard treatments like colchicine, which is used for conditions like Familial Mediterranean Fever to prevent inflammation and amyloidosis. ^{1 2 3 4 5}

Research Team

Michael A Levine, MD

Principal Investigator

Children'sHospital of Philadelphia

Eligibility Criteria

This trial is for individuals aged 6 months to 65 years with genetic disorders causing high calcium in blood/urine due to CYP24A1 mutations. They must have normal or elevated vitamin D3 and low parathyroid hormone levels. Excluded are those allergic to rifampin, on conflicting meds, pregnant/breastfeeding, or with significant liver/kidney disease.

Inclusion Criteria

I am between 6 months and 65 years old.

My calcium levels are higher than normal.

My tests show a CYP24A1 mutation.

Exclusion Criteria

Pregnancy or breastfeeding

Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures

Your liver or kidney function tests show significant abnormalities, with levels more than twice the normal limit for certain substances in the blood.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Observation

Participants are observed for baseline measurements and initial assessment

8 weeks

Baseline and every 4 weeks

Treatment

Participants receive escalating doses of rifampin (5 and 10 mg/kg/day) to assess effect, safety, and tolerability

16 weeks

Baseline and every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Every 4 weeks

Treatment Details

Interventions

• Rifampin

Trial Overview The study tests the effectiveness of rifampin in treating high calcium levels in blood and urine linked to specific genetic mutations. Participants will take rifampin for 16 weeks to see if it helps manage their condition.

Participant Groups

Group I: All Subjects Experimental Treatment 1 Intervention

SingleArm: Escalating doses of rifampin (5 and 10 mg/kg/day) (SingleArm)

Rifampin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Rifampin for:

• Tuberculosis
• Meningitis
• Osteomyelitis
• Brucellosis
• Legionnaires' disease

Approved in European Union as Rifampicin for:

• Tuberculosis
• Meningitis
• Osteomyelitis
• Brucellosis
• Legionnaires' disease

Approved in Canada as Rifampin for:

• Tuberculosis
• Meningitis
• Osteomyelitis
• Brucellosis
• Legionnaires' disease

Who Is Running the Clinical Trial?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

Familial Mediterranean fever (FMF) is a hereditary inflammatory disease caused by mutations in the MEFV gene, leading to uncontrolled inflammation and potentially severe complications like amyloidosis and chronic renal failure.

Daily colchicine treatment is effective in managing FMF, providing complete remission or significant reduction in symptoms for most patients, and it also helps prevent the development of renal amyloidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Familial Mediterranean fever. Onen, F.[2022]

A 9-year-old boy was diagnosed with both Familial Mediterranean Fever (FMF) and Gitelman syndrome, highlighting the importance of genetic testing for accurate diagnosis in patients with overlapping symptoms.

The patient was effectively managed with oral potassium and magnesium supplements alongside colchicine for FMF, demonstrating a successful treatment strategy for managing both conditions simultaneously.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concomitance of Familial Mediterranean Fever and Gitelman syndrome in an adolescent. Atmış, B., Kışla-Ekinci, RM., Melek, E., et al.[2020]

Familial Mediterranean fever (FMF) is a genetic condition primarily affecting populations around the Mediterranean, characterized by recurrent inflammatory attacks, and can lead to severe complications like amyloidosis and renal failure.

Colchicine is the standard treatment for FMF, effectively controlling attacks and preventing amyloidosis in most patients; however, 5-10% of patients do not respond to this treatment, highlighting the need for new therapeutic options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Familial mediterranean fever - a review and update. Orbach, H., Ben-Chetrit, E.[2022]

In a study of 110 patients with familial Mediterranean fever (FMF), those who did not respond to colchicine treatment had significantly lower concentrations of colchicine in their mononuclear cells compared to responders, suggesting that treatment failure may be linked to inadequate drug levels in these cells.

Both responders and nonresponders primarily carried the M694V mutation in the MEFV gene, but nonresponders tended to come from lower socioeconomic backgrounds and had a more severe form of the disease, indicating that factors beyond genetics may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colchicine nonresponsiveness in familial Mediterranean fever: clinical, genetic, pharmacokinetic, and socioeconomic characterization. Lidar, M., Scherrmann, JM., Shinar, Y., et al.[2022]

Familial Mediterranean fever (FMF) is an under-diagnosed hereditary auto-inflammatory disorder primarily affecting populations around the Mediterranean, caused by mutations in the MEFV gene that regulates inflammation.

Colchicine remains the only effective treatment for preventing acute FMF episodes and the associated risk of amyloidosis, despite the emergence of alternative therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Familial Mediterranean fever: an ancient hereditary disease]. Nucera, G., La Regina, M., Diaco, M., et al.[2006]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Familial Mediterranean fever. [2022]

2. Turkey pubmed.ncbi.nlm.nih.gov

Concomitance of Familial Mediterranean Fever and Gitelman syndrome in an adolescent. [2020]

3. Italy pubmed.ncbi.nlm.nih.gov

Familial mediterranean fever - a review and update. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Colchicine nonresponsiveness in familial Mediterranean fever: clinical, genetic, pharmacokinetic, and socioeconomic characterization. [2022]

5. Italy pubmed.ncbi.nlm.nih.gov

[Familial Mediterranean fever: an ancient hereditary disease]. [2006]