Cystic Fibrosis Related Bone Disease
Conditions
Keywords
Cystic fibrosis related bone disease, Cystic fibrosis, Ivacaftor
Brief summary
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.
Detailed 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.
Interventions
None listed
Sponsors
Boston Children's Hospital
Massachusetts General Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
6 Years to 75 Years
Healthy volunteers
Yes
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bone Microarchitecture and Strength Measures of the Radius and Tibia | Baseline and 24 months | Change in cortical volumetric bone mineral density at the radius |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Areal Bone Mineral Density as Measured by DXA | Baseline and 24 months | Change in PA spine bone mineral density |
| Bone Turnover Markers | Baseline and 24 months | Change in osteocalcin |
Countries
United States
Participant flow
Recruitment details
27 subjects with CF taking ivacaftor were enrolled; however, 1 subject dropped out immediately after signing the consent form prior to any study procedures. No baseline data were obtained in this subject. Therefore, 26 subjects with CF taking ivacaftor were followed prospectively and were matched to the other 2 cohorts.
Participants by arm
| Arm | Count |
|---|---|
| Subjects With CF Taking Ivacaftor Subjects with CF ages 6 to 75 years old who will be or have started taking ivacaftor within the previous 6 months | 26 |
| Subjects With CF Not Taking Ivacaftor Subjects with CF ages 6 to 75 years old who will not be taking ivacaftor, matched for age, race, and gender with cohort 1 | 26 |
| Healthy Subjects 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. | 26 |
| Total | 78 |
Baseline characteristics
| Characteristic | Subjects With CF Taking Ivacaftor | Subjects With CF Not Taking Ivacaftor | Healthy Subjects | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 11 Participants | 11 Participants | 11 Participants | 33 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 15 Participants | 15 Participants | 45 Participants |
| Age, Continuous | 23.1 years STANDARD_DEVIATION 13.1 | 22.8 years STANDARD_DEVIATION 13.1 | 23.8 years STANDARD_DEVIATION 13.2 | 23.3 years STANDARD_DEVIATION 13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 26 Participants | 26 Participants | 78 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 26 Participants | 26 Participants | 26 Participants | 78 Participants |
| Region of Enrollment United States | 26 participants | 26 participants | 26 participants | 78 participants |
| Sex: Female, Male Female | 15 Participants | 15 Participants | 15 Participants | 45 Participants |
| Sex: Female, Male Male | 11 Participants | 11 Participants | 11 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 26 | 0 / 26 |
| other Total, other adverse events | 0 / 26 | 1 / 26 | 0 / 26 |
| serious Total, serious adverse events | 0 / 26 | 0 / 26 | 0 / 26 |
Outcome results
Primary
Bone Microarchitecture and Strength Measures of the Radius and Tibia
Change in cortical volumetric bone mineral density at the radius
Time frame: Baseline and 24 months
Population: Subjects who were lost to follow up prior to the 24 month visit were not included in the analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects With CF Taking Ivacaftor | Bone Microarchitecture and Strength Measures of the Radius and Tibia | 44.6 mgHA/cm3 | Standard Deviation 53.9 |
| Subjects With CF Not Taking Ivacaftor | Bone Microarchitecture and Strength Measures of the Radius and Tibia | 40.1 mgHA/cm3 | Standard Deviation 44 |
| Healthy Subjects | Bone Microarchitecture and Strength Measures of the Radius and Tibia | 43.7 mgHA/cm3 | Standard Deviation 53.8 |
Comparison: Change from baseline to 24 months in cortical volumentric bone mineral density was determined and compared between subjects with CF taking ivacaftor and subjects with CF not taking ivacaftor.p-value: 0.77t-test, 2 sided
Comparison: Change from baseline to 24 months in cortical volumentric bone mineral density was determined and compared between subjects with CF not taking ivacaftor and healthy subjects.p-value: 0.82t-test, 2 sided
Secondary
Areal Bone Mineral Density as Measured by DXA
Change in PA spine bone mineral density
Time frame: Baseline and 24 months
Population: Subjects who were lost to follow up prior to the 24 month visit were not included in the analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects With CF Taking Ivacaftor | Areal Bone Mineral Density as Measured by DXA | 0.032 g/cm2 | Standard Deviation 0.058 |
| Subjects With CF Not Taking Ivacaftor | Areal Bone Mineral Density as Measured by DXA | 0.024 g/cm2 | Standard Deviation 0.043 |
| Healthy Subjects | Areal Bone Mineral Density as Measured by DXA | 0.029 g/cm2 | Standard Deviation 0.043 |
Comparison: Change from baseline to 24 months in DXA PA spine bone mineral density was determined and compared between subjects with CF taking ivacaftor and subjects with CF not taking ivacaftor.p-value: 0.64t-test, 2 sided
Comparison: Change from baseline to 24 months in DXA PA spine bone mineral density was determined and compared between subjects with CF not taking ivacaftor and healthy subjects.p-value: 0.78t-test, 2 sided
Secondary
Bone Turnover Markers
Change in osteocalcin
Time frame: Baseline and 24 months
Population: Subjects who were lost to follow up prior to the 24 month visit were not included in the analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects With CF Taking Ivacaftor | Bone Turnover Markers | -5.36 ng/ml | Standard Deviation 12.89 |
| Subjects With CF Not Taking Ivacaftor | Bone Turnover Markers | -4.51 ng/ml | Standard Deviation 16.27 |
| Healthy Subjects | Bone Turnover Markers | -4.5 ng/ml | Standard Deviation 14.55 |
Comparison: Change from baseline to 24 months in osteocalcin was determined and compared between subjects with CF taking ivacaftor and subjects with CF not taking ivacaftor.p-value: 0.86t-test, 2 sided
Comparison: Change from baseline to 24 months in osteocalcin was determined and compared between subjects with CF not taking ivacaftor and healthy subjects.p-value: 0.99t-test, 2 sided