Study of Alendronate to Prevent and Treat Osteoporosis in Cystic Fibrosis Patients
Information source: McMaster University
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cystic Fibrosis; Osteoporosis; Bone Diseases, Metabolic
Intervention: Alendronate (Drug); Placebo (Drug)
Phase: Phase 4
Sponsored by: McMaster University
Official(s) and/or principal investigator(s):
Alexandra Papaioannou, M.D., Principal Investigator, Affiliation: McMaster University
Andreas Freitag, M.D., Study Chair, Affiliation: McMaster University
Jonathan D Adachi, M.D., Study Chair, Affiliation: McMaster University
The primary objective of this study is to determine efficacy of 70 mg alendronate once
weekly compared to placebo. This will be measured by percent changes in lumbar spine(LS)
bone mineral density(BMD) in adult cystic fibrosis(CF)patients after one year of treatment.
The investigators hypothesize that in adult CF patients with osteopenia or osteoporosis,
alendronate 70 mg once weekly will produce a mean increase from baseline in lumbar spine BMD
that is greater than that observed with placebo at 12 months.
Official title: A Multicentre, Double-Blind, Randomized Placebo-Controlled Study of 70mg Alendronate Once Weekly for the Prevention and Treatment of Osteoporosis in Canadian Adult Cystic Fibrosis Patients
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: To determine efficacy of 70 mg alendronate once weekly compared to placebo, measured by changes in LS BMD in adult CF patients after one year of treatment
To determine the efficacy of 70 mg alendronate once weekly compared to placebo measured by percent changes in total hip BMD, proximal femur BMD, and N-telopeptide at one year in adult CF patients.
To determine health-related quality of life (HRQL) using the SF-36 instrument.
To determine HRQL using the Cystic Fibrosis Questionnaire (CFQ).
To determine the safety of 70 mg of alendronate given once weekly compared with placebo in adult CF patients
To determine correlations between BMD and patient characteristics, including but not limited to the following: corticosteroid use, height, weight, body mass index BMI) and forced expired volume in 1 minute (FEV1).
Randomized controled trial have begun to establish the efficacy and safety of
bisphosphonates in CF patients with decreased BMD. The development of a once weekly dosing
regimen of alendronate and the low prevalence of esophageal adverse events may be an
advantageous therapeutic option for this high-risk population. This is a one-year
randomized, double-blind, placebo-controlled, multicentre study in 55 CF patients with
osteopenia or osteoporosis. Six Canadian centres are participating in this study. Patients
randomized to treatment will receive 70 mg oral alendronate once weekly, while controls will
receive identical placebo once weekly. All medication dispensed will be concealed. There
will be no dose modification during the course of the trial. All patients will receive a
total of 1000 mg calcium, 500 through supplementation and 500 through diet. All patients
will continue to take vitamin D supplementation ( 2 tablets per day, 400 IU vitamin
Minimum age: 18 Years.
Maximum age: N/A.
1. CF; confirmed by a positive sweat test or DNA analysis
2. age 18 years or above at the time of informed consent
3. osteopenia (-2. 5< BMD t-score<1. 0) or osteoporosis (BMD t-score <-2. 5)t-score at the
LS (1-4)or total hip
4. provision of informed consent
1. endoscopy-proven esophagitis, gastritis, ulceration, or abnormalities of the
esophagus which delay esophageal emptying such as stricture, achalasia, or esophageal
2. significantly impaired renal function; this is defined as serum creatinine >177
3. current or recent (within 1 year prior to randomization) consumption of an excess of
alcohol or abuse of drugs; an excess of alcohol is defined as more than four of any
of the following per day, or a combination of more that four of the following per
day: 30 mL distilled spirits, 240 mL beer, or 120 mL wine
4. history of prior organ transplantation
5. any condition which may interfere with the evaluation of LS BMD as determined in a
screening radiograph by a radiologist at the central facility e. g. spinal fusion,
confluent aortic calcifications, surgical artefact, excessive osteophytes, or other
permanent artefact; hip prostheses or any other condition that may interfere with the
evaluation of hip BMD
6. participation in another clinical trial 30 days prior to enrolment or within 6
half-lives of the study drug if applicable
7. pregnancy, lactation, or a desire to become pregnant; safe effective birthcontrol
must be used
8. know hypersensitivity or abnormal reaction to study drug or other bisphosphonates
9. use of drugs know to affect bone within 6 months of starting trial medication (e. g.
thiazide, diuretics, calcitonin, calcitriol, anabolic steroids, estrogen or
estrogen-related drugs (e. g. tamoxifen, raloxifene, tibolone high dose vaginal
estrogen), progesterone, fluoride: this does not include the birth control pill
10. patients currently receiving another bisphosphonate in whom treatment efficacy has
been established; only patients who are intolerant to or did not respond to another
bisphosphonate will be considered for inclusion; patients must have ceased treatment
with any bisphosphonate for at least 1 year prior to enrolment
11. use of systemic corticosteroids at a dose of at least 7. 5 mg/day or greater within
last 6 months
12. concomitant use of any investigational drug other than the study medication
13. current or recent (within 1 year prior to randomization) metabolic bone disorders
other than secondary osteoporosis, such as Paget's disease, renal osteodystrophy,
osteomalacia (25-OHD<25nmol/L), hypoparathyroidism, hyperparathyroidism; TSH outside
normal laboratory range, with values that are assessed as clinically significant by
the investigator; if on replacement therapy, dose should be stable and TSH within
normal range for a minimum of 6 weeks prior to trial enrolment
14. hypocalcemia from any cause, corrected for low albumin
15. any history of cancer; for relatively benign skin malignancies, such as basal cell
carcinoma or squamous cell carcinoma and patients with a history of successfully
treated cervical carcinoma in istu, a documented six-month remission is required
before study entry
16. poor medical or psychiatric risk for treatment with an investigational drug
Locations and Contacts
Dr. Harvey Rabin - Health Sciences Centre, Calgary, Alberta T2N 4N1, Canada
McMaster University, Hamilton, Ontario, Canada
London Health Sciences Centre, London, Ontario N6A 4G5, Canada
Centre de Recherche - CHUM, Montreal, Quebec H2W 1T7, Canada
Montreal Chest Institute, Montreal, Quebec H2X 2P4, Canada
CHUL Hospital, Sainte-Foy, Quebec G1V 4G2, Canada
Aris RM, Lester GE, Caminiti M, Blackwood AD, Hensler M, Lark RK, Hecker TM, Renner JB, Guillen U, Brown SA, Neuringer IP, Chalermskulrat W, Ontjes DA. Efficacy of alendronate in adults with cystic fibrosis with low bone density. Am J Respir Crit Care Med. 2004 Jan 1;169(1):77-82. Epub 2003 Oct 16.
Aris RM, Merkel PA, Bachrach LK, Borowitz DS, Boyle MP, Elkin SL, Guise TA, Hardin DS, Haworth CS, Holick MF, Joseph PM, O'Brien K, Tullis E, Watts NB, White TB. Guide to bone health and disease in cystic fibrosis. J Clin Endocrinol Metab. 2005 Mar;90(3):1888-96. Epub 2004 Dec 21. Review.
Starting date: December 2003
Last updated: October 22, 2008