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

Cystic Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00157690
• Other study ID #: MK-0217 Protocol 214
• Status: Completed
• Phase: Phase 4
• First received: September 8, 2005
• Last updated: October 22, 2008
• Start date: December 2003
• Est. completion date: August 2006

Study information

• Verified date: October 2008
• Source: McMaster University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: August 2006
• Est. primary completion date: August 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Bone Diseases
• Bone Diseases, Metabolic
• Cystic Fibrosis
• Fibrosis
• Metabolic Diseases
• Osteoporosis

Intervention

Drug:
• Alendronate
70 mg 1x weekly for 12 months
• Placebo
70 mg 1 x weekly for 12 months

Locations

Country	Name	City	State
Canada	Dr. Harvey Rabin - Health Sciences Centre	Calgary	Alberta
Canada	McMaster University	Hamilton	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	Centre de Recherche - CHUM	Montreal	Quebec
Canada	Montreal Chest Institute	Montreal	Quebec
Canada	CHUL Hospital	Sainte-Foy	Quebec

Sponsors (7)

Lead Sponsor	Collaborator
McMaster University	Centre hospitalier de l'Université de Montréal (CHUM), Laval University, London Health Sciences Centre, McGill University, Merck Frosst Canada Ltd., University of Calgary

Country where clinical trial is conducted

Canada, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		12 months	No
Secondary	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.		12 months	No
Secondary	To determine health-related quality of life (HRQL) using the SF-36 instrument.		12 months	No
Secondary	To determine HRQL using the Cystic Fibrosis Questionnaire (CFQ).		12 months	No
Secondary	To determine the safety of 70 mg of alendronate given once weekly compared with placebo in adult CF patients		12 months	Yes
Secondary	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).		12 months	No