search
Back to results

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

Primary Purpose

Osteoporosis, Cystic Fibrosis

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Alendronate
Placebo
Sponsored by
Istituto Auxologico Italiano
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteoporosis focused on measuring cystic fibrosis, children, adolescents, low bone mass, osteoporosis, alendronate, fractures

Eligibility Criteria

5 Years - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • CRR Fibrosi Cistica, Divisione Gastroenterologia, Ospedale Bambin Gesù
  • CRR Fibrosi Cistica, Unità Operativa di Pediatria, Ospedale Misericordia
  • CRR Fibrosi Cistica, Clinica Pediatrica, Policlinico Universitario di Messina
  • Istituto Auxologico Italiano IRCCS
  • Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano
  • CRR Fibrosi Cistica, Dipartimento Pediatria, Università Federico II
  • CRR Fibrosi Cistica Adulti, Azienda Ospedaliera Universitaria San Luigi Gonzaga
  • CRR Fibrosi Cistica, Ospedale dei Bambini, ARNAS Civico
  • CRR Fibrosi Cistica, Dipartimento di Pediatria, Policlinico Umberto I
  • CRR Fibrosi Cistica, Divisione di Pediatria, Istituto Burlo Garofolo
  • CRR Fibrosi Cistica, Azienda Ospedalierouniversitaria di Verona

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Alendronate

Placebo

Arm Description

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.

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).

Outcomes

Primary Outcome Measures

Bone mineral density increase at lumbar spine.
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.
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.
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.
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.)

Full Information

First Posted
March 14, 2013
Last Updated
March 5, 2014
Sponsor
Istituto Auxologico Italiano
Collaborators
Fondazione Telethon
search

1. Study Identification

Unique Protocol Identification Number
NCT01812551
Brief Title
Treatment of Low Bone Density in Cystic Fibrosis.
Acronym
OSCYF
Official Title
Osteoporosis in Cystic Fibrosis: Study of Bone Mass and Bone Metabolism, and Prospective Randomized Therapeutic Trial.
Study Type
Interventional

2. Study Status

Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
October 2002 (undefined)
Primary Completion Date
July 2006 (Actual)
Study Completion Date
July 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Istituto Auxologico Italiano
Collaborators
Fondazione Telethon

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoporosis, Cystic Fibrosis
Keywords
cystic fibrosis, children, adolescents, low bone mass, osteoporosis, alendronate, fractures

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
171 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Alendronate
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Alendronate
Other Intervention Name(s)
Alendros
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo was distributed to the patients in plain bottles and boxes (bearing only the center and patient codes).
Primary Outcome Measure Information:
Title
Bone mineral density increase at lumbar spine.
Description
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.
Time Frame
up to 24 months
Secondary Outcome Measure Information:
Title
Changes in bone turnover markers.
Description
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).
Time Frame
baseline and up to 24 months
Title
Fracture rate.
Description
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.
Time Frame
at 12th and 24th month
Title
Adverse effects of alendronate.
Description
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.)
Time Frame
continuously throughout Phase 2 (2nd year of study)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maria Luisa Bianchi, M.D.
Organizational Affiliation
Istituto Auxologico Italiano
Official's Role
Principal Investigator
Facility Information:
Facility Name
CRR Fibrosi Cistica, Divisione Gastroenterologia, Ospedale Bambin Gesù
City
Città del Vaticano
Country
Holy See (Vatican City State)
Facility Name
CRR Fibrosi Cistica, Unità Operativa di Pediatria, Ospedale Misericordia
City
Grosseto
Country
Italy
Facility Name
CRR Fibrosi Cistica, Clinica Pediatrica, Policlinico Universitario di Messina
City
Messina
Country
Italy
Facility Name
Istituto Auxologico Italiano IRCCS
City
Milano
ZIP/Postal Code
20145
Country
Italy
Facility Name
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano
City
Milano
Country
Italy
Facility Name
CRR Fibrosi Cistica, Dipartimento Pediatria, Università Federico II
City
Napoli
Country
Italy
Facility Name
CRR Fibrosi Cistica Adulti, Azienda Ospedaliera Universitaria San Luigi Gonzaga
City
Orbassano
Country
Italy
Facility Name
CRR Fibrosi Cistica, Ospedale dei Bambini, ARNAS Civico
City
Palermo
Country
Italy
Facility Name
CRR Fibrosi Cistica, Dipartimento di Pediatria, Policlinico Umberto I
City
Roma
Country
Italy
Facility Name
CRR Fibrosi Cistica, Divisione di Pediatria, Istituto Burlo Garofolo
City
Trieste
Country
Italy
Facility Name
CRR Fibrosi Cistica, Azienda Ospedalierouniversitaria di Verona
City
Verona
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
8346485
Citation
Grey AB, Ames RW, Matthews RD, Reid IR. Bone mineral density and body composition in adult patients with cystic fibrosis. Thorax. 1993 Jun;48(6):589-93. doi: 10.1136/thx.48.6.589.
Results Reference
background
PubMed Identifier
8551418
Citation
Henderson RC, Madsen CD. Bone density in children and adolescents with cystic fibrosis. J Pediatr. 1996 Jan;128(1):28-34. doi: 10.1016/s0022-3476(96)70424-9.
Results Reference
background
PubMed Identifier
8545201
Citation
Bhudhikanok GS, Lim J, Marcus R, Harkins A, Moss RB, Bachrach LK. Correlates of osteopenia in patients with cystic fibrosis. Pediatrics. 1996 Jan;97(1):103-11.
Results Reference
background
PubMed Identifier
9078542
Citation
Baroncelli GI, De Luca F, Magazzu G, Arrigo T, Sferlazzas C, Catena C, Bertelloni S, Saggese G. Bone demineralization in cystic fibrosis: evidence of imbalance between bone formation and degradation. Pediatr Res. 1997 Mar;41(3):397-403. doi: 10.1203/00006450-199703000-00016.
Results Reference
background
PubMed Identifier
9569551
Citation
Humphries IR, Allen JR, Waters DL, Howman-Giles R, Gaskin KJ. Volumetric bone mineral density in children with cystic fibrosis. Appl Radiat Isot. 1998 May-Jun;49(5-6):593-5. doi: 10.1016/s0969-8043(97)00203-0. No abstract available.
Results Reference
background
PubMed Identifier
9454526
Citation
Aris RM, Renner JB, Winders AD, Buell HE, Riggs DB, Lester GE, Ontjes DA. Increased rate of fractures and severe kyphosis: sequelae of living into adulthood with cystic fibrosis. Ann Intern Med. 1998 Feb 1;128(3):186-93. doi: 10.7326/0003-4819-128-3-199802010-00004.
Results Reference
background
PubMed Identifier
9672505
Citation
Bhudhikanok GS, Wang MC, Marcus R, Harkins A, Moss RB, Bachrach LK. Bone acquisition and loss in children and adults with cystic fibrosis: a longitudinal study. J Pediatr. 1998 Jul;133(1):18-27. doi: 10.1016/s0022-3476(98)70172-6.
Results Reference
background
PubMed Identifier
10088930
Citation
Henderson RC, Madsen CD. Bone mineral content and body composition in children and young adults with cystic fibrosis. Pediatr Pulmonol. 1999 Feb;27(2):80-4. doi: 10.1002/(sici)1099-0496(199902)27:23.0.co;2-j.
Results Reference
background
PubMed Identifier
11014345
Citation
Bianchi ML, Cimaz R, Bardare M, Zulian F, Lepore L, Boncompagni A, Galbiati E, Corona F, Luisetto G, Giuntini D, Picco P, Brandi ML, Falcini F. Efficacy and safety of alendronate for the treatment of osteoporosis in diffuse connective tissue diseases in children: a prospective multicenter study. Arthritis Rheum. 2000 Sep;43(9):1960-6. doi: 10.1002/1529-0131(200009)43:93.0.CO;2-J.
Results Reference
background
PubMed Identifier
9279333
Citation
Brumsen C, Hamdy NA, Papapoulos SE. Long-term effects of bisphosphonates on the growing skeleton. Studies of young patients with severe osteoporosis. Medicine (Baltimore). 1997 Jul;76(4):266-83. doi: 10.1097/00005792-199707000-00005.
Results Reference
background
PubMed Identifier
9753709
Citation
Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G, Travers R. Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med. 1998 Oct 1;339(14):947-52. doi: 10.1056/NEJM199810013391402.
Results Reference
background
PubMed Identifier
24429202
Citation
Bianchi ML, Colombo C, Assael BM, Dubini A, Lombardo M, Quattrucci S, Bella S, Collura M, Messore B, Raia V, Poli F, Bini R, Albanese CV, De Rose V, Costantini D, Romano G, Pustorino E, Magazzu G, Bertasi S, Lucidi V, Traverso G, Coruzzo A, Grzejdziak AD. Treatment of low bone density in young people with cystic fibrosis: a multicentre, prospective, open-label observational study of calcium and calcifediol followed by a randomised placebo-controlled trial of alendronate. Lancet Respir Med. 2013 Jul;1(5):377-85. doi: 10.1016/S2213-2600(13)70064-X. Epub 2013 Jun 2.
Results Reference
derived

Learn more about this trial

Treatment of Low Bone Density in Cystic Fibrosis.

We'll reach out to this number within 24 hrs