The Effect of Alendronate, Calcium, and Vitamin D on Bone Mineral Density in HIV Infected Patients

HIV Infections Clinical Trial

Official title:

A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Once-Weekly Alendronate in HIV-Infected Subjects With Decreased Bone Mineral Density Receiving Calcium and Vitamin D

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00061256
• Other study ID #: ACTG A5163
• Secondary ID: DAIDS-ES ID 1008
• Status: Completed
• Phase: Phase 2
• First received: May 22, 2003
• Last updated: August 6, 2009
• Est. completion date: September 2006

Study information

• Verified date: August 2009
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

Alendronate is a drug that is used to treat osteoporosis. The purpose of this study is to examine whether alendronate in combination with calcium and vitamin D is safe and effective for treating bone loss in people with HIV.

Description:

Decreased bone mineral density (BMD) has been identified in up to 50% of HIV infected men, with severe osteoporosis in up to 21% of these men. The mechanisms underlying these bone abnormalities remain unclear. Bisphosphonates are potent bone resorption inhibitors and have been shown to be effective in treating osteoporosis. While several bisphosphonates are approved for the treatment of osteoporosis in women, alendronate is the only bisphosphonate approved for treatment in men. This study hypothesizes that alendronate will be able to reverse decreased BMD secondary to inhibition of bone resorption in HIV infected patients treated with potent antiretroviral therapy, and that these patients will be able to tolerate alendronate without any significant toxicities. The study will also examine the efficacy of once-weekly alendronate with daily calcium and vitamin D in both men and women with HIV.

Patients will participate in this study for 48 weeks. Patients will be randomly assigned to receive either alendronate or placebo. All patients will receive calcium and vitamin D. Dual energy x-ray absorptiometry (DEXA) scans will be used to evaluate bone density at each visit. After study entry, patients will have visits at Weeks 2, 12, 24, 36, and 48. During these visits, blood will be drawn and a pregnancy test may be performed. Patients must fast for at least 8 hours prior to the entry visit and for the visits at Weeks 2, 12, 24, and 48.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: September 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 25 Years and older

Eligibility

Inclusion Criteria

• HIV-1 infection

• Lumbar spine DEXA scan confirming decreased BMD within 90 days prior to study entry

• CD4 cell count 100 cells/mm3 or more within 30 days prior to study entry

• Stable antiretroviral regimen for at least 12 weeks prior to study entry

• No plans to alter antiretroviral therapy or to initiate structured/strategic treatment interruptions

• No plans to significantly alter exercise habits or diet for the duration of the study

• Documentation of two consecutive measurements of viral load of 5000 copies/ml or less within 90 days prior to study entry, with at least one of the two values obtained within 30 days prior to study entry

• Willing to use acceptable methods of contraception

• For women with the absence of menses for at least 6 months, serum prolactin level in the normal range within 60 days prior to study entry

• For women taking estrogen therapy, stable estrogen regimen for at least 24 weeks prior to study entry, with no plan to change estrogen dose for the duration of the study

• Serum calcium between 8 mg/dl and 11 mg/dl within 30 days prior to study entry

Exclusion Criteria

• Men with untreated low total serum testosterone levels within 60 days prior to study entry, or men with plans to initiate testosterone replacement during the study

• Cannot receive vitamin D or calcium supplements

• Daily vitamin or dietary supplements that include 10,000 IU or greater of vitamin A within 90 days prior to study entry

• Hyperparathyroidism, vitamin D deficiency, or oral thrush within 60 days prior to study entry

• Any current or past conditions that predispose to disorders involving the esophagus. Participants with a history of mild or controlled reflux may be enrolled.

• Esophagitis within 6 months prior to study entry

• Pregnant or breastfeeding

• Paget's disease

• Spinal fracture (thoracic or lumbar spine) within 60 days prior to study entry

• Atraumatic bone fracture at any time since 18 years of age

• Spinal fracture at any time in the past

• Inability to stand or sit upright for at least 30 minutes

• Use of systemic glucocorticoids for a cumulative duration of longer than 4 weeks within 6 months immediately prior to study entry

• Use of medications for treatment of osteoporosis within 12 months prior to study entry

• Allergy/hypersensitivity to any component of alendronate, the components of the tablet, or bisphosphonate compounds

• Active drug or alcohol dependence which, in the opinion of the investigator, would interfere with adherence to study requirements or would endanger the patient's health while on study

• Hospitalization for alcohol-related liver disease at any time in the past

• Current use of systemic cytotoxic chemotherapy

• Acute illness within 30 days prior to study entry which, in the opinion of the investigator, would interfere with participation in the study

• History of hepatitis C virus infection

• For participants using anabolic steroids, use of steroids for less than 6 months prior to entry or plans to change current regimen during the course of the study; if a steroid regimen has been discontinued, it must have been discontinued at least 6 months prior to entry

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Alendronate

• Calcium carbonate

• Vitamin D

Locations

Country	Name	City	State
United States	University of Alabama-Birmingham	Birmingham	Alabama
United States	Univ of North Carolina	Chapel Hill	North Carolina
United States	Cook County Hospital Core Center	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	Case Western Reserve Univ	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Univ of Texas, Galveston	Galveston	Texas
United States	Indiana Univ Hosp	Indianapolis	Indiana
United States	Methodist Hosp of Indiana	Indianapolis	Indiana
United States	Wishard Hosp	Indianapolis	Indiana
United States	UCLA School of Medicine	Los Angeles	California
United States	Univ of Minnesota	Minneapolis	Minnesota
United States	Comprehensive Care Clinic	Nashville	Tennessee
United States	Chelsea Clinic	New York	New York
United States	NYU/Bellevue	New York	New York
United States	Nebraska Health System	Omaha	Nebraska
United States	University of Pennsylvania, Philadelphia	Philadelphia	Pennsylvania
United States	Rhode Island Hosp	Providence	Rhode Island
United States	Stanley Street Treatment and Resource	Providence	Rhode Island
United States	The Miriam Hosp	Providence	Rhode Island
United States	AIDS Community Health Center	Rochester	New York
United States	Univ of Rochester Med Ctr	Rochester	New York
United States	University of California, San Diego	San Diego	California
United States	San Francisco General Hospital	San Francisco	California
United States	University of Washington (Seattle)	Seattle	Washington
United States	Stanford Univ	Stanford	California
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (5)

Mondy K, Tebas P. Emerging bone problems in patients infected with human immunodeficiency virus. Clin Infect Dis. 2003 Apr 1;36(Suppl 2):S101-5. — View Citation

Orwoll E, Ettinger M, Weiss S, Miller P, Kendler D, Graham J, Adami S, Weber K, Lorenc R, Pietschmann P, Vandormael K, Lombardi A. Alendronate for the treatment of osteoporosis in men. N Engl J Med. 2000 Aug 31;343(9):604-10. — View Citation

Reid IR. The roles of calcium and vitamin D in the prevention of osteoporosis. Endocrinol Metab Clin North Am. 1998 Jun;27(2):389-98. Review. — View Citation

Schnitzer T, Bone HG, Crepaldi G, Adami S, McClung M, Kiel D, Felsenberg D, Recker RR, Tonino RP, Roux C, Pinchera A, Foldes AJ, Greenspan SL, Levine MA, Emkey R, Santora AC 2nd, Kaur A, Thompson DE, Yates J, Orloff JJ. Therapeutic equivalence of alendronate 70 mg once-weekly and alendronate 10 mg daily in the treatment of osteoporosis. Alendronate Once-Weekly Study Group. Aging (Milano). 2000 Feb;12(1):1-12. — View Citation

Tebas P, Powderly WG, Claxton S, Marin D, Tantisiriwat W, Teitelbaum SL, Yarasheski KE. Accelerated bone mineral loss in HIV-infected patients receiving potent antiretroviral therapy. AIDS. 2000 Mar 10;14(4):F63-7. — View Citation

External Links

•   Click here for more information about alendronate.
•   Click here for more information about calcium carbonate.
•   Haga clic aquí para ver información sobre este ensayo clínico en español.