Treatment of Low Bone Density in Cystic Fibrosis. (OSCYF)

This study has been completed.
Sponsor:
Collaborator:
Fondazione Telethon
Information provided by (Responsible Party):
Maria Luisa Bianchi, Istituto Auxologico Italiano
ClinicalTrials.gov Identifier:
NCT01812551
First received: March 14, 2013
Last updated: March 5, 2014
Last verified: March 2014
  Purpose

Cystic fibrosis (CF) -- an autosomal recessive genetic disease affecting about 60,000 individuals worldwide, including about 3,800 in Italy -- is often associated with low bone mineral mass. The current aggressive therapies have ensured a much longer survival of CF patients but this has led to a higher frequency of osteoporosis and bone fractures, a serious problem which not only affects quality of life, but also hinders further therapeutic measures.

The aim of this study, conducted on a large group of children, adolescents and young adults with CF, has been the evaluation of bone mass changes after 1 year of a simple treatment with RDA-adjusted dietary calcium plus 25-OH vitamin D supplementation, and the feasibility and efficacy of alendronate treatment (for another year) in patients not responding to calcium + 25-OH vitamin D alone.


Condition Intervention Phase
Osteoporosis
Cystic Fibrosis
Drug: Alendronate
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Osteoporosis in Cystic Fibrosis: Study of Bone Mass and Bone Metabolism, and Prospective Randomized Therapeutic Trial.

Resource links provided by NLM:


Further study details as provided by Istituto Auxologico Italiano:

Primary Outcome Measures:
  • Bone mineral density increase at lumbar spine. [ Time Frame: up to 24 months ] [ Designated as safety issue: No ]

    Bone mineral density evaluated by DXA. Bone mineral apparent density calculated to correct for bone size (growing subjects). Z-score calculated.

    Measurements: Phase 1 (171 subjects): Baseline, 6 months, 12 months. Phase 2 (128 subjects, randomized to 2 arms: placebo or alendronate): 18 months, 24 months.



Secondary Outcome Measures:
  • Changes in bone turnover markers. [ Time Frame: baseline and up to 24 months ] [ Designated as safety issue: No ]
    Bone turnover markers: (serum) osteocalcin (OC), bone specific alkaline phosphatase (BSAP), C-terminal telopeptide of procollagen 1 (CTx); (urine) terminal telopeptide of procollagen 1 (NTx).

  • Fracture rate. [ Time Frame: at 12th and 24th month ] [ Designated as safety issue: No ]

    Appendicular fractures were evaluated at baseline (previous fractures) and throughout the 2 years of study (incident fractures) with X-rays.

    Vertebral fractures were evaluated at the end of Phase 1 (12th month) and at the end of Phase 2 (24th month) with lateral thoracic and lumbar spine X-rays.


  • Adverse effects of alendronate. [ Time Frame: continuously throughout Phase 2 (2nd year of study) ] [ Designated as safety issue: Yes ]
    Evaluated on the basis of lab tests (calcemia, calciuria, blood cell count, liver and kidney function), FEV1 changes, and other signs/symptoms (e.g. pain, fever, etc.)


Enrollment: 171
Study Start Date: October 2002
Study Completion Date: July 2007
Primary Completion Date: July 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Alendronate

128 subjects participated in the study's Phase 2 (1-year double-blind, randomized, placebo-controlled, parallel group study).

65 subjects were randomized to this arm. Oral alendronate dose: 5 mg/day, if body weight ≤25 kg; 10 mg/day, if body weight >25 kg.

Drug: Alendronate
As active drug, we used Alendros (Abiogen Pharma, Pisa, Italy), distributed to the patients in plain bottles and boxes (bearing only the center and patient codes).
Other Name: Alendros
Placebo Comparator: Placebo

128 subjects participated in the study's Phase 2 (1-year double-blind, randomized, placebo-controlled, parallel group study).

63 subjects were randomized to this arm. Oral placebo (inactive pills).

Drug: Placebo
Placebo was distributed to the patients in plain bottles and boxes (bearing only the center and patient codes).

Detailed Description:

The study included 2 phases.

Phase 1 (1-year open-label observational study): following baseline evaluation, bone mass changes have been studied with a simple therapy of adequate calcium intake and 25-OH vitamin D supplements in all eligible subjects (N=171).

Phase 2 (1-year double-blind, randomized, placebo-controlled, parallel group study): the 128 subjects showing an insufficient response to calcium + 25-OH vitamin D alone (bone mass increase <5%) at the end of Phase 1, were randomized into 2 groups and assigned to alendronate treatment (N=65) or placebo (N=63) (in addition to calcium and 25-OH vitamin D as during Phase 1).

The study has been carried out by the Coordinator's Institution (Istituto Auxologico Italiano)in collaboration with most Regional Reference Centers for CF in Italy.

  Eligibility

Ages Eligible for Study:   5 Years to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age 2-30 years
  • clinically stable condition
  • regular menses in females
  • low Bone Mineral Apparent Density for age (defined as BMAD Z-score ≤-2.0 if age ≤18 years or ≤-2.5 if age >18 years).

Exclusion Criteria:

  • two or more episodes of hypercalcemia and/or hypercalciuria
  • contraindications to 25-OH vitamin D or alendronate treatment
  • recent transplantation
  • other diseases or medications (glucocorticoids excepted) associated with bone loss.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01812551

Locations
Holy See (Vatican City State)
CRR Fibrosi Cistica, Divisione Gastroenterologia, Ospedale Bambin Gesù
Città del Vaticano, Holy See (Vatican City State)
Italy
CRR Fibrosi Cistica, Unità Operativa di Pediatria, Ospedale Misericordia
Grosseto, Italy
CRR Fibrosi Cistica, Clinica Pediatrica, Policlinico Universitario di Messina
Messina, Italy
Istituto Auxologico Italiano IRCCS
Milano, Italy, 20145
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano
Milano, Italy
CRR Fibrosi Cistica, Dipartimento Pediatria, Università Federico II
Napoli, Italy
CRR Fibrosi Cistica Adulti, Azienda Ospedaliera Universitaria San Luigi Gonzaga
Orbassano, Italy
CRR Fibrosi Cistica, Ospedale dei Bambini, ARNAS Civico
Palermo, Italy
CRR Fibrosi Cistica, Dipartimento di Pediatria, Policlinico Umberto I
Roma, Italy
CRR Fibrosi Cistica, Divisione di Pediatria, Istituto Burlo Garofolo
Trieste, Italy
CRR Fibrosi Cistica, Azienda Ospedalierouniversitaria di Verona
Verona, Italy
Sponsors and Collaborators
Istituto Auxologico Italiano
Fondazione Telethon
Investigators
Principal Investigator: Maria Luisa Bianchi, M.D. Istituto Auxologico Italiano
  More Information

Additional Information:
Publications:

Responsible Party: Maria Luisa Bianchi, MD, First level manager, Istituto Auxologico Italiano
ClinicalTrials.gov Identifier: NCT01812551     History of Changes
Other Study ID Numbers: 02A001
Study First Received: March 14, 2013
Last Updated: March 5, 2014
Health Authority: Italy: Ministry of Health

Keywords provided by Istituto Auxologico Italiano:
cystic fibrosis
children
adolescents
low bone mass
osteoporosis
alendronate
fractures

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Osteoporosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Alendronate
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014