Treatment of Low Bone Density in Cystic Fibrosis.

NCT01812551 | Completed Phase 3

• 1 other identifier: 02A001
• Study Type: interventional
• Target: 171
• Locations: 2 countries
• Sites: 11

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.

Conditions

Osteoporosis; Cystic Fibrosis

Keywords

cystic fibrosis; children; adolescents; low bone mass; osteoporosis; alendronate; fractures

Outcome Measures

Primary Outcomes (1)

• 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.

  up to 24 months

Secondary Outcomes (3)

• Changes in bone turnover markers.

  baseline and up to 24 months

• Fracture rate.

  at 12th and 24th month

• Adverse effects of alendronate.

  continuously throughout Phase 2 (2nd year of study)

Study Arms (2)

Alendronate

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Alendronate 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).

Also known as: Alendros

Alendronate

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 5 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Istituto Auxologico Italiano: lead
• Fondazione Telethon: collaborator

Study Sites (11)

CRR Fibrosi Cistica, Divisione Gastroenterologia, Ospedale Bambin Gesù

Vatican City, Holy See

Location

CRR Fibrosi Cistica, Unità Operativa di Pediatria, Ospedale Misericordia

Grosseto, Italy

Location

CRR Fibrosi Cistica, Clinica Pediatrica, Policlinico Universitario di Messina

Messina, Italy

Location

Istituto Auxologico Italiano IRCCS

Milan, 20145, Italy

Location

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

Milan, Italy

Location

CRR Fibrosi Cistica, Dipartimento Pediatria, Università Federico II

Napoli, Italy

Location

CRR Fibrosi Cistica Adulti, Azienda Ospedaliera Universitaria San Luigi Gonzaga

Orbassano, Italy

Location

CRR Fibrosi Cistica, Ospedale dei Bambini, ARNAS Civico

Palermo, Italy

Location

CRR Fibrosi Cistica, Dipartimento di Pediatria, Policlinico Umberto I

Roma, Italy

Location

CRR Fibrosi Cistica, Divisione di Pediatria, Istituto Burlo Garofolo

Trieste, Italy

Location

CRR Fibrosi Cistica, Azienda Ospedalierouniversitaria di Verona

Verona, Italy

Location

Related Publications (12)

• 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.

  PMID: 8346485 BACKGROUND

• 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.

  PMID: 8551418 BACKGROUND

• 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.

  PMID: 8545201 BACKGROUND

• 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.

  PMID: 9078542 BACKGROUND

• 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.

  PMID: 9569551 BACKGROUND

• 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.

  PMID: 9454526 BACKGROUND

• 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.

  PMID: 9672505 BACKGROUND

• 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.

  PMID: 10088930 BACKGROUND

• 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.

  PMID: 11014345 BACKGROUND

• 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.

  PMID: 9279333 BACKGROUND

• 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.

  PMID: 9753709 BACKGROUND

• 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.

  PMID: 24429202 DERIVED

Related Links

• Study protocol
• Lab test information

MeSH Terms

Conditions

Osteoporosis; Cystic Fibrosis; Fractures, Bone

Interventions

Alendronate

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals

Study Officials

• Maria Luisa Bianchi, M.D.

  Istituto Auxologico Italiano

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, First level manager

Study Record Dates

• First Submitted: March 14, 2013
• First Posted: March 18, 2013
• Study Start: October 1, 2002
• Primary Completion: July 1, 2006
• Study Completion: July 1, 2007
• Last Updated: March 6, 2014

Record last verified: 2014-03

Locations

IT (10); HO (1)