Study of Alendronate to Prevent and Treat Osteoporosis in Cystic Fibrosis Patients

This study has been completed.
Sponsor:
Collaborators:
Centre hospitalier de l'Université de Montréal (CHUM)
London Health Sciences Centre
University of Calgary
McGill University
Laval University
Merck Frosst Canada Ltd.
Information provided by:
McMaster University
ClinicalTrials.gov Identifier:
NCT00157690
First received: September 8, 2005
Last updated: October 22, 2008
Last verified: October 2008
  Purpose

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.


Condition Intervention Phase
Cystic Fibrosis
Osteoporosis
Bone Diseases, Metabolic
Drug: Alendronate
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by McMaster University:

Primary Outcome Measures:
  • 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 [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • To determine health-related quality of life (HRQL) using the SF-36 instrument. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • To determine HRQL using the Cystic Fibrosis Questionnaire (CFQ). [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • To determine the safety of 70 mg of alendronate given once weekly compared with placebo in adult CF patients [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • 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). [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 56
Study Start Date: December 2003
Study Completion Date: August 2006
Primary Completion Date: August 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Alendronate
Drug: Alendronate
70 mg 1x weekly for 12 months
Other Name: Fosamax
Placebo Comparator: 2
Placebo
Drug: Placebo
70 mg 1 x weekly for 12 months

Detailed Description:

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 D/tablet).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  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

Exclusion Criteria:

  1. endoscopy-proven esophagitis, gastritis, ulceration, or abnormalities of the esophagus which delay esophageal emptying such as stricture, achalasia, or esophageal varices
  2. significantly impaired renal function; this is defined as serum creatinine >177 umol/L
  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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00157690

Locations
Canada, Alberta
Dr. Harvey Rabin - Health Sciences Centre
Calgary, Alberta, Canada, T2N 4N1
Canada, Ontario
McMaster University
Hamilton, Ontario, Canada
London Health Sciences Centre
London, Ontario, Canada, N6A 4G5
Canada, Quebec
Centre de Recherche - CHUM
Montreal, Quebec, Canada, H2W 1T7
Montreal Chest Institute
Montreal, Quebec, Canada, H2X 2P4
CHUL Hospital
Sainte-Foy, Quebec, Canada, G1V 4G2
Sponsors and Collaborators
McMaster University
Centre hospitalier de l'Université de Montréal (CHUM)
London Health Sciences Centre
University of Calgary
McGill University
Laval University
Merck Frosst Canada Ltd.
Investigators
Principal Investigator: Alexandra Papaioannou, M.D. McMaster University
Study Chair: Andreas Freitag, M.D. McMaster University
Study Chair: Jonathan D Adachi, M.D. McMaster University
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr. Alexandra Papaioannou, McMaster University
ClinicalTrials.gov Identifier: NCT00157690     History of Changes
Other Study ID Numbers: MK-0217 Protocol 214
Study First Received: September 8, 2005
Last Updated: October 22, 2008
Health Authority: Canada: Health Canada

Keywords provided by McMaster University:
Alendronate
Bisphosphonates
Cystic Fibrosis
Osteoporosis

Additional relevant MeSH terms:
Fibrosis
Osteoporosis
Cystic Fibrosis
Bone Diseases
Metabolic Diseases
Bone Diseases, Metabolic
Pathologic Processes
Musculoskeletal Diseases
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Alendronate
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014