Cystic Fibrosis Related Bone Disease: the Role of CFTR

This study is currently recruiting participants.
Verified November 2013 by Massachusetts General Hospital
Sponsor:
Collaborator:
Children's Hospital Boston
Information provided by (Responsible Party):
Joel S. Finkelstein, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01549314
First received: March 2, 2012
Last updated: November 22, 2013
Last verified: November 2013
  Purpose

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.


Condition
Cystic Fibrosis Related Bone Disease

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Cystic Fibrosis Related Bone Disease: the Role of CFTR

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Bone microarchitecture and strength measures of the radius and tibia [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Areal bone mineral density as measured by DXA [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Bone turnover markers [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

Plasma and urine


Estimated Enrollment: 90
Study Start Date: April 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
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
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
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.

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.

  Eligibility

Ages Eligible for Study:   6 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Subjects with CF will be recruited from the Cystic Fibrosis Centers at Children's Hospital Boston and Massachusetts General Hospital. Healthy subjects will be a community sample recruited from nearby communities.

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01549314

Contacts
Contact: Melissa S Putman, MD 857-218-5017 msputman@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Melissa S Putman, MD    857-218-5017    msputman@partners.org   
Sponsors and Collaborators
Massachusetts General Hospital
Children's Hospital Boston
Investigators
Principal Investigator: Joel Finkelstein, MD Massachusetts General Hospital
  More Information

Publications:
Responsible Party: Joel S. Finkelstein, MD, Associate Professor of Medicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01549314     History of Changes
Other Study ID Numbers: MGH 2012P000269
Study First Received: March 2, 2012
Last Updated: November 22, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Cystic fibrosis related bone disease
Cystic fibrosis
Ivacaftor

Additional relevant MeSH terms:
Bone Diseases
Cystic Fibrosis
Fibrosis
Musculoskeletal Diseases
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on April 16, 2014