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

NCT ID: NCT00157690

Last Updated: 2008-10-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-12-31
• Study Completion Date: 2006-08-31

Brief 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.

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).

Conditions

Cystic Fibrosis; Osteoporosis; Bone Diseases, Metabolic

Keywords

Alendronate; Bisphosphonates; Cystic Fibrosis; Osteoporosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Alendronate

Group Type: ACTIVE_COMPARATOR

Alendronate

Intervention Type: DRUG

70 mg 1x weekly for 12 months

2

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

70 mg 1 x weekly for 12 months

Interventions

Alendronate

70 mg 1x weekly for 12 months

Intervention Type: DRUG

Placebo

70 mg 1 x weekly for 12 months

Intervention Type: DRUG

Other Intervention Names

Fosamax

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre hospitalier de l'Université de Montréal (CHUM)

OTHER

Sponsor Role: collaborator

London Health Sciences Centre

OTHER

Sponsor Role: collaborator

University of Calgary

OTHER

Sponsor Role: collaborator

McGill University

OTHER

Sponsor Role: collaborator

Laval University

OTHER

Sponsor Role: collaborator

Merck Frosst Canada Ltd.

INDUSTRY

Sponsor Role: collaborator

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

McMaster University

Principal Investigators

Alexandra Papaioannou, M.D.

Role: PRINCIPAL_INVESTIGATOR

McMaster University

Andreas Freitag, M.D.

Role: STUDY_CHAIR

McMaster University

Jonathan D Adachi, M.D.

Role: STUDY_CHAIR

McMaster University

Locations

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, Canada

Countries

Canada

References

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. doi: 10.1164/rccm.200307-1049OC. Epub 2003 Oct 16.

Reference Type: BACKGROUND

PMID: 14563654 (View on PubMed)

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. doi: 10.1210/jc.2004-1629. Epub 2004 Dec 21.

Reference Type: BACKGROUND

PMID: 15613415 (View on PubMed)

Papaioannou A, Kennedy CC, Freitag A, Ioannidis G, O'Neill J, Webber C, Pui M, Berthiaume Y, Rabin HR, Paterson N, Jeanneret A, Matouk E, Villeneuve J, Nixon M, Adachi JD. Alendronate once weekly for the prevention and treatment of bone loss in Canadian adult cystic fibrosis patients (CFOS trial). Chest. 2008 Oct;134(4):794-800. doi: 10.1378/chest.08-0608. Epub 2008 Jul 18.

Reference Type: DERIVED

PMID: 18641106 (View on PubMed)

Other Identifiers

MK-0217 Protocol 214

Identifier Type: -

Identifier Source: org_study_id