Treatment of Low Bone Density in Cystic Fibrosis.

Phase 3

Completed

• Conditions: Osteoporosis; Cystic Fibrosis
• Interventions: Drug: Placebo; Drug: Alendronate

• Registration Number: NCT01812551
• Lead Sponsor: Istituto Auxologico Italiano

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.

Study Timeline

• Study Start: 2002-10
• Primary Completion: 2006-07
• Study Completion: 2007-07
• Study First Submitted: 2013-03-14
• Study First Submitted QC: 2013-03-15
• Study First Posted: 2013-03-18
• Status Verified: 2014-03
• Last Update Submitted: 2014-03-05
• Last Update Posted: 2014-03-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 171

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).

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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).
Alendronate	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.

Primary Outcome Measures

Name	Time	Method
Bone mineral density increase at lumbar spine.	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

Name	Time	Method
Changes in bone turnover markers.	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.	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.	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.)

Trial Locations

Locations (11)

CRR Fibrosi Cistica, Unità Operativa di Pediatria, Ospedale Misericordia; 🇮🇹 Grosseto, Italy

CRR Fibrosi Cistica, Clinica Pediatrica, Policlinico Universitario di Messina; 🇮🇹 Messina, 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, Divisione di Pediatria, Istituto Burlo Garofolo; 🇮🇹 Trieste, Italy

CRR Fibrosi Cistica, Azienda Ospedalierouniversitaria di Verona; 🇮🇹 Verona, Italy

CRR Fibrosi Cistica, Dipartimento di Pediatria, Policlinico Umberto I; 🇮🇹 Roma, Italy

Istituto Auxologico Italiano IRCCS; 🇮🇹 Milano, Italy

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano; 🇮🇹 Milano, Italy

CRR Fibrosi Cistica, Divisione Gastroenterologia, Ospedale Bambin Gesù; 🇻🇦 Città del Vaticano, Holy See (Vatican City State)