Treatment of Low Bone Density in Cystic Fibrosis.

NCT ID: NCT01812551

Last Updated: 2014-03-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

171 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-10-31

Study Completion Date

2007-07-31

Brief Summary

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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

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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.

Conditions

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Osteoporosis Cystic Fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Alendronate

Intervention Type DRUG

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).

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).

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Interventions

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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).

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Other Intervention Names

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Alendros

Eligibility Criteria

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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.
Minimum Eligible Age

5 Years

Maximum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fondazione Telethon

OTHER

Sponsor Role collaborator

Istituto Auxologico Italiano

OTHER

Sponsor Role lead

Responsible Party

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Maria Luisa Bianchi

MD, First level manager

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Maria Luisa Bianchi, M.D.

Role: PRINCIPAL_INVESTIGATOR

Istituto Auxologico Italiano

Locations

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CRR Fibrosi Cistica, Divisione Gastroenterologia, Ospedale Bambin Gesù

Vatican City, , Holy See

Site Status

CRR Fibrosi Cistica, Unità Operativa di Pediatria, Ospedale Misericordia

Grosseto, , Italy

Site Status

CRR Fibrosi Cistica, Clinica Pediatrica, Policlinico Universitario di Messina

Messina, , Italy

Site Status

Istituto Auxologico Italiano IRCCS

Milan, , Italy

Site Status

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano

Milan, , Italy

Site Status

CRR Fibrosi Cistica, Dipartimento Pediatria, Università Federico II

Napoli, , Italy

Site Status

CRR Fibrosi Cistica Adulti, Azienda Ospedaliera Universitaria San Luigi Gonzaga

Orbassano, , Italy

Site Status

CRR Fibrosi Cistica, Ospedale dei Bambini, ARNAS Civico

Palermo, , Italy

Site Status

CRR Fibrosi Cistica, Dipartimento di Pediatria, Policlinico Umberto I

Roma, , Italy

Site Status

CRR Fibrosi Cistica, Divisione di Pediatria, Istituto Burlo Garofolo

Trieste, , Italy

Site Status

CRR Fibrosi Cistica, Azienda Ospedalierouniversitaria di Verona

Verona, , Italy

Site Status

Countries

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Holy See Italy

References

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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.

Reference Type BACKGROUND
PMID: 8346485 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8551418 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8545201 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9078542 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9569551 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9454526 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9672505 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10088930 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11014345 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9279333 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9753709 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24429202 (View on PubMed)

Related Links

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Other Identifiers

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02A001

Identifier Type: -

Identifier Source: org_study_id

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