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

March 5, 2014 updated by: Maria Luisa Bianchi, Istituto Auxologico Italiano

Osteoporosis in Cystic Fibrosis: Study of Bone Mass and Bone Metabolism, and Prospective Randomized Therapeutic Trial.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

171

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Holy See (Vatican City State)
      • Città del Vaticano, Holy See (Vatican City State)
        • CRR Fibrosi Cistica, Divisione Gastroenterologia, Ospedale Bambin Gesù
  • Italy
      • Grosseto, Italy
        • CRR Fibrosi Cistica, Unità Operativa di Pediatria, Ospedale Misericordia
      • Messina, Italy
        • CRR Fibrosi Cistica, Clinica Pediatrica, Policlinico Universitario di Messina
      • Milano, Italy, 20145
        • Istituto Auxologico Italiano IRCCS
      • Milano, Italy
        • Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano
      • Napoli, Italy
        • CRR Fibrosi Cistica, Dipartimento Pediatria, Università Federico II
      • Orbassano, Italy
        • CRR Fibrosi Cistica Adulti, Azienda Ospedaliera Universitaria San Luigi Gonzaga
      • Palermo, Italy
        • CRR Fibrosi Cistica, Ospedale dei Bambini, ARNAS Civico
      • Roma, Italy
        • CRR Fibrosi Cistica, Dipartimento di Pediatria, Policlinico Umberto I
      • Trieste, Italy
        • CRR Fibrosi Cistica, Divisione di Pediatria, Istituto Burlo Garofolo
      • Verona, Italy
        • CRR Fibrosi Cistica, Azienda Ospedalierouniversitaria di Verona

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years to 30 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bone mineral density increase at lumbar spine.
Time Frame: up to 24 months

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.
up to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in bone turnover markers.
Time Frame: baseline and up to 24 months
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).
baseline and up to 24 months
Fracture rate.
Time Frame: at 12th and 24th month

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.
at 12th and 24th month
Adverse effects of alendronate.
Time Frame: continuously throughout Phase 2 (2nd year of study)
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.)
continuously throughout Phase 2 (2nd year of study)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istituto Auxologico Italiano

Collaborators

Fondazione Telethon

Investigators

  • Principal Investigator: Maria Luisa Bianchi, M.D., Istituto Auxologico Italiano

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2002

Primary Completion (Actual)

July 1, 2006

Study Completion (Actual)

July 1, 2007

Study Registration Dates

First Submitted

March 14, 2013

First Submitted That Met QC Criteria

March 15, 2013

First Posted (Estimate)

March 18, 2013

Study Record Updates

Last Update Posted (Estimate)

March 6, 2014

Last Update Submitted That Met QC Criteria

March 5, 2014

Last Verified

March 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 02A001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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