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

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ClinicalTrials.gov Identifier: NCT01812551

Recruitment Status : Completed

First Posted : March 18, 2013

Last Update Posted : March 6, 2014

Sponsor:

Collaborator:

Fondazione Telethon

Information provided by (Responsible Party):

Maria Luisa Bianchi, Istituto Auxologico Italiano

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.

Condition or disease	Intervention/treatment	Phase
Osteoporosis Cystic Fibrosis	Drug: Alendronate Drug: Placebo	Phase 3

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	171 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Osteoporosis in Cystic Fibrosis: Study of Bone Mass and Bone Metabolism, and Prospective Randomized Therapeutic Trial.
Study Start Date :	October 2002
Actual Primary Completion Date :	July 2006
Actual Study Completion Date :	July 2007

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Cystic fibrosis

MedlinePlus related topics: Bone Density Cystic Fibrosis Osteoporosis

Drug Information available for: Alendronic acid Alendronate sodium

Genetic and Rare Diseases Information Center resources: Cystic Fibrosis

U.S. FDA Resources

Arms and Interventions

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 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).

Outcome Measures

Primary Outcome Measures :

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.

Secondary Outcome Measures :

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).
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.
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.)

Eligibility Criteria

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Ages Eligible for Study:	5 Years to 30 Years (Child, Adult)
Sexes Eligible for Study:	All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01812551

Locations

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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

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

More Information

Publications:

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.

Henderson RC, Madsen CD. Bone density in children and adolescents with cystic fibrosis. J Pediatr. 1996 Jan;128(1):28-34.

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.

Baroncelli GI, De Luca F, Magazzú 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.

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.

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.

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.

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.

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.

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. Review.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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, Magazzù 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.

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Responsible Party:	Maria Luisa Bianchi, MD, First level manager, Istituto Auxologico Italiano
ClinicalTrials.gov Identifier:	NCT01812551
Other Study ID Numbers:	02A001
First Posted:	March 18, 2013 Key Record Dates
Last Update Posted:	March 6, 2014
Last Verified:	March 2014

Keywords provided by Maria Luisa Bianchi, Istituto Auxologico Italiano:


cystic fibrosis children adolescents low bone mass	osteoporosis alendronate fractures

Additional relevant MeSH terms:

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

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