Cystic Fibrosis Related Bone Disease: the Role of CFTR

Mass General Brigham

Status: Completed

Conditions: Cystic Fibrosis Related Bone Disease

Study type: Observational

Funder types: Other

Identifiers

NCT01549314

MGH 2012P000269

Details and patient eligibility

About

The purpose of this study is to determine whether ivacaftor, a recently FDA-approved CFTR potentiator, improves bone micro-architecture and strength in patients with cystic fibrosis with at least one G551D CFTR mutation.

Full description

Ivacaftor, a CFTR potentiator, has recently been FDA approved for the treatment of cystic fibrosis in patients with at least one G551D CFTR mutation. Given the possible role of CFTR in bone, we hypothesize that this medication may also improve bone health in CF patients. The purpose of this study is to test this hypothesis using high resolution peripheral quantitative computed tomography, a research tool that measures bone micro-architecture and volumetric bone density and has the ability to detect small changes in bone that might otherwise be missed with standard bone imaging techniques such as bone density testing.

Enrollment: 79 patients

Sex: All

Ages: 6 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

COHORT 1

Inclusion Criteria:

• Age 6 to 75 years old
• Established diagnosis of CF with at least one abnormal G551D-CFTR allele
• Eligibility for and intent to start treatment with ivacaftor or started treatment with ivacaftor within previous 6 months

Exclusion Criteria:

• Psychiatric or mental incapacity that would preclude subject from assenting to study participation
• Current pregnancy
• History of organ transplantation
• History of Burkholderia dolosa infection

COHORT 2:

Subjects will be grouped by gender, age and race to match subjects in Cohort 1 within two years. Pubertal subjects will be matched by Tanner stage.

Inclusion Criteria:

• Age 6 to 75 years old
• Established diagnosis of CF

Exclusion Criteria:

• Psychiatric or mental incapacity that would preclude subject from assenting to study participation
• Current pregnancy
• History of organ transplantation
• History of Burkholderia dolosa infection

COHORT 3:

Subjects will be grouped by gender, age and race to match subjects in Cohort 2 within two years. Pubertal subjects will be matched by Tanner stage.

Inclusion criteria:

• Age 6 to 75 years old
• Clinically stable, deemed able to complete the screening, baseline, and scheduled study visits.

Exclusion criteria:

• History of significant cardiac, renal, pulmonary, hepatic, or malignant disease, current alcohol or illicit drug abuse, or major psychiatric disorder
• Current diagnoses known to affect bone metabolism, including cystic fibrosis, osteoporosis, amenorrhea >3 months (in menstruating women who are not taking oral contraceptives or have an IUD), hyperthyroidism, diabetes, hyperparathyroidism, Paget's disease, kidney stones, chronic inflammatory diseases, malabsorptive disorders, malnutrition, prolonged immobility, and skeletal dysplasias
• History of a non-digital fracture in the previous 6 months, history of one pathologic fracture, or greater than four total lifetime non-digital fractures
• Cumulative lifetime use of oral glucocorticoids for greater than 2 months
• Current or prior use of medications known to affect bone metabolism including hormone replacement therapy, anti-estrogens, bisphosphonates, calcitonin, fluoride, lithium, suppressive doses of levothyroxine, or anticonvulsants.
• Pregnancy
• BMI less than 18.5 or greater than 30 kg/m2 in subjects 18 years and older, or BMI less than 5th or greater than 95th percentile in subjects under the age of 18 years.
• Any medical or psychiatric condition or situation that would compromise subject safety, informed consent/assent, treatment compliance, follow-up measurements, or data quality

Trial design

79 participants in 3 patient groups

Subjects with CF taking ivacaftor

Description:

Subjects with CF ages 6 to 75 years old who will be or have started taking ivacaftor within the previous 6 months

Subjects with CF not taking ivacaftor

Description:

Subjects with CF ages 6 to 75 years old who will not be taking ivacaftor, matched for age, race, and gender with cohort 1

Healthy subjects

Description:

Healthy subjects with no medical conditions known to affect bone between the ages of 6 to 75 years old, matched for age, race, and gender with cohort 2.