Cinacalcet for Fibroblast Growth Factor 23 (FGF23)-Mediated Hypophosphatemia (Hypophosphatemic Rickets)

This study is currently recruiting participants.
Verified August 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Dental and Craniofacial Research (NIDCR) )
ClinicalTrials.gov Identifier:
NCT01748812
First received: December 11, 2012
Last updated: March 14, 2014
Last verified: August 2013
  Purpose

Background:

  • Hypophosphatemia is a condition where a person has low levels of phosphorus in the blood. Low blood phosphorus can cause muscle and bone weakness (such as rickets) and teeth problems. One cause of the condition is having too much fibroblast growth factor 23 (FGF23). FGF23 is a hormone that causes the kidney to get rid of phosphorus in the urine. It can also prevent the body from making vitamin D, which helps the body absorb phosphorus in food.
  • Many people with low blood phosphorus take high doses of phosphorus and calcium medications. However, one side effect of these drugs is increased blood levels of parathyroid hormone (PTH). The drug cinacalcet can help lower PTH levels, which may decrease the amount of phosphorus lost in the urine and increase the phosphorus levels in the blood. Researchers want to see if cinacalcet can help blood phosphorus and decrease the amount of phosphorus supplements that people need to take.

Objectives:

- To see if cinacalcet can be a safe and effective treatment for people with low phosphorus conditions due to high FGF23.

Eligibility:

- Individuals between 18 and 70 years of age who have different forms of hypophosphatemic rickets and tumor-induced hypophosphatemia

Design:

  • Participants will have up to 25 study visits over about 28 weeks.
  • Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
  • Up to three more lab visits for blood and urine tests will be required before treatment. Imaging studies of the bones, spine, and kidneys will be performed.
  • Participants will have a 3-night hospital stay to start treatment. They will take cinacalcet once a day. Treatment will be monitored with frequent blood tests and imaging studies.
  • Participants will continue to take cinacalcet once a day for 3 weeks. They will have regular study visits to monitor the treatment.
  • There will be up to two other overnight hospital stays (1 to 3 nights) to adjust cinacalcet doses. The dose will increase until the maximum dose is reached, or side effects develop.
  • After the end of the cinacalcet study, participants will have several more followup visits to monitor the effects of treatment.

Condition Intervention Phase
Osteomalacia
Drug: Osteomalacia
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-label Dose-titration Study of the Tolerability and Efficacy of Cinacalcet to Treat Fibroblast Growth Factor 23 (FGF23)-Mediated Hypophosphatemia

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Evaluate the tolerability of cinacalcet in individuals with FGF23-mediated hypophosphatemia [ Time Frame: 4 years ]

Secondary Outcome Measures:
  • To explore the effectiveness of cinacalcet at decreaing renal phosphate wasting [ Time Frame: 4 years ]
  • Evaluate the pharmacodynamics of cinacalcet in this subject population. [ Time Frame: 4 years ]

Estimated Enrollment: 17
Study Start Date: November 2012
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Osteomalacia
    N/A
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. < TAB> Chronological age: 18-70 years
    2. < TAB> Diagnosis of a genetic form of FGF23-mediated hypophosphatemia:

      1. < TAB> X-linked hypophosphatemic rickets (XLH)
      2. < TAB> Autosomal dominant hypophosphatemic rickets (ADHR)
      3. < TAB> Autosomal recessive hypophosphatemic rickets (ARHR)

      Or, diagnosis of a non-genetic form of FGF23-mediated hypophosphatemia, i.e. tumor-induced osteomalacia (TIO)

    3. < TAB> Ability to understand and provide informed consent
    4. < TAB> Ability to complete the protocol scheduled assessments and medication regimen
    5. < TAB> Women of child-bearing potential (not surgically sterile via tubal ligation, bilateral oophorectomy or hysterectomy, or who are not postmenopausal for greater than or equal to 1 year) must agree to practice adequate contraception that may include, but is not limited to, abstinence, monogamous relationship with vasectomized partner, barrier methods such as condoms, diaphragms, spermicides, intrauterine devices, and licensed hormonal methods for the duration of the treatment portion of the study.

EXCLUSION CRITERIA:

  1. < TAB> Chronic or recurrent hypocalcemia defined by a serum calcium < 8.4 mg/dL (2.1 mmol/L)
  2. < TAB> Tertiary hyperparathyroidism as evidenced by concurrent PTH and calcium levels above the upper limit of normal
  3. < TAB> History of parathyroid surgery and/or hypoparathyroidism
  4. < TAB> Hypercalciuria as defined as > 4 mg/kg/day (0.1 mmol/kg/day) on optimized conventional therapy (as determined during SOC optimization phase)
  5. < TAB> Moderate to severe hepatic insufficiency as defined by total bilirubin > 2 mg/dL and serum albumin < 3 g/dL and International Normalized Ratio (INR) > 2 OR presence of ascites or hepatic encephalopathy.
  6. < TAB> A calculated eGFR < 50 mL/min/1.73 m(2), using the CKD-EPI equation
  7. < TAB> History of a non-febrile seizure disorder
  8. < TAB> History of a clinically significant cardiac arrhythmia
  9. < TAB> History of chronic gastrointestinal disease
  10. < TAB> Current therapy (at the time of informed consent) bisphosphonates, calcitonin, diuretics or medications that may have a significant drug interaction with cinacalcet
  11. < TAB> Known hypersensitivity to cinacalcet or any of its constituents
  12. < TAB> Positive pregnancy test or lactation
  13. < TAB> Use of another investigational agent (i.e., in the context of a clinical trial, use of an investigational product that may have impact on the study) within the last 3 months
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01748812

Contacts
Contact: Diala M El-Maouche, M.D. (301) 435-6280 elmaouched@mail.nih.gov
Contact: Rachel I Gafni, M.D. (301) 594-9924 gafnir@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Rachel I Gafni, M.D. National Institute of Dental and Craniofacial Research (NIDCR)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Dental and Craniofacial Research (NIDCR) )
ClinicalTrials.gov Identifier: NCT01748812     History of Changes
Other Study ID Numbers: 130025, 13-D-0025
Study First Received: December 11, 2012
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Tumor Induced Osteomalacia
Hypophosphatemic Rickets

Additional relevant MeSH terms:
Hypophosphatemic Rickets, X-Linked Dominant
Rickets
Osteomalacia
Hypophosphatemia
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Calcium Metabolism Disorders
Metabolic Diseases
Vitamin D Deficiency
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Phosphorus Metabolism Disorders
Hypophosphatemia, Familial
Renal Tubular Transport, Inborn Errors
Kidney Diseases
Urologic Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 16, 2014