Clinical trial NCT01812551: Treatment of Low Bone Density in Cystic Fibrosis.
Official title: Osteoporosis in Cystic Fibrosis: Study of Bone Mass and Bone Metabolism, and Prospective Randomized Therapeutic Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoporosis
Cystic Fibrosis
Keywords: cystic fibrosis
children
adolescents
low bone mass
osteoporosis
alendronate
fractures
Lead sponsor: Istituto Auxologico Italiano
Sponsor class: OTHER
Collaborators: name: Fondazione Telethon
First posted: 2013-03-18
Enrollment: 171
Sex: ALL
Minimum age (years): 5
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Bone mineral density increase at lumbar spine.
timeFrame: up to 24 months
Secondary outcomes:
measure: Changes in bone turnover markers.
timeFrame: baseline and up to 24 months
measure: Fracture rate.
timeFrame: at 12th and 24th month
measure: Adverse effects of alendronate.
timeFrame: continuously throughout Phase 2 (2nd year of study)
Other outcomes:
Locations:
city: Città del Vaticano
country: Holy See (Vatican City State)
facility: CRR Fibrosi Cistica, Divisione Gastroenterologia, Ospedale Bambin Gesù
city: Grosseto
country: Italy
facility: CRR Fibrosi Cistica, Unità Operativa di Pediatria, Ospedale Misericordia
city: Messina
country: Italy
facility: CRR Fibrosi Cistica, Clinica Pediatrica, Policlinico Universitario di Messina
city: Milano
country: Italy
facility: Istituto Auxologico Italiano IRCCS
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano
city: Napoli
country: Italy
facility: CRR Fibrosi Cistica, Dipartimento Pediatria, Università Federico II
city: Orbassano
country: Italy
facility: CRR Fibrosi Cistica Adulti, Azienda Ospedaliera Universitaria San Luigi Gonzaga
city: Palermo
country: Italy
facility: CRR Fibrosi Cistica, Ospedale dei Bambini, ARNAS Civico
city: Roma
country: Italy
facility: CRR Fibrosi Cistica, Dipartimento di Pediatria, Policlinico Umberto I
city: Trieste
country: Italy
facility: CRR Fibrosi Cistica, Divisione di Pediatria, Istituto Burlo Garofolo
city: Verona
country: Italy
facility: CRR Fibrosi Cistica, Azienda Ospedalierouniversitaria di Verona
Study officials:
affiliation: Istituto Auxologico Italiano
name: Maria Luisa Bianchi, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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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.
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.
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.
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.
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.
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.