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Safety and Effectiveness of Alendronate for Bone Mineral Density in HIV-infected Children and Adolescents

This study has been completed.
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00921557
First received: June 12, 2009
Last updated: February 8, 2017
Last verified: February 2017
Results First Received: December 15, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Participant, Care Provider;   Primary Purpose: Treatment
Condition: HIV Infection
Interventions: Drug: Alendronate
Drug: Placebo
Dietary Supplement: Calcium carbonate/vitamin D

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Fifty-two (52) study participants were recruited between November 5, 2009 and March 27, 2014, at 10 study sites: 8 in the United States and 2 in Brazil.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Children and adolescents were randomly assigned to 3 treatment sequence groups. Two participants were enrolled, but because their baseline lumbar spine bone mineral density z-score was greater than -1.5 at their baseline visit, they never started study treatment and were taken off the study.

Reporting Groups
  Description
1A: Alendronate/Alendronate Participants received alendronate for 96 weeks
1B: Alendronate/Placebo Participants received alendronate for 48 weeks followed by placebo for 48 weeks
2: Placebo/Alendronate Participants received placebo for 48 weeks followed by alendronate for 48 weeks

Participant Flow:   Overall Study
    1A: Alendronate/Alendronate   1B: Alendronate/Placebo   2: Placebo/Alendronate
STARTED   17   17   18 
Started Study Treatment   15   17   18 
COMPLETED   15 [1]   17 [1]   18 [1] 
NOT COMPLETED   2   0   0 
Baseline lumbar spine >-1.5                2                0                0 
[1] Completed 48 weeks



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Includes participants who took at least one dose of study treatment (alendronate/placebo)

Reporting Groups
  Description
1A: Alendronate/Alendronate Participants received alendronate for 96 weeks
1B: Alendronate/Placebo Participants received alendronate for 48 weeks followed by placebo for 48 weeks
2: Placebo/Alendronate Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Total Total of all reporting groups

Baseline Measures
   1A: Alendronate/Alendronate   1B: Alendronate/Placebo   2: Placebo/Alendronate   Total 
Overall Participants Analyzed 
[Units: Participants]
 15   17   18   50 
Age 
[Units: Years]
Median (Full Range)
       
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
   16 
 (11 to 23) 
 16 
 (12 to 23) 
 16 
 (11 to 22) 
 16 
 (11 to 23) 
Age, Customized 
[Units: Participants]
Count of Participants
       
11 - < 15 years         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
11 - < 15 years   7   4   6   17 
15 - < 19 years         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
15 - < 19 years   6   9   8   23 
>= 19 years         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
>= 19 years   2   4   4   10 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
Female      5  33.3%      6  35.3%      5  27.8%      16  32.0% 
Male      10  66.7%      11  64.7%      13  72.2%      34  68.0% 
Race/Ethnicity, Customized 
[Units: Participants]
Count of Participants
       
White non-Hispanic         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
White non-Hispanic   3   3   1   7 
Black non-Hispanic         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
Black non-Hispanic   2   4   1   7 
Hispanic (regardless of race)         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
Hispanic (regardless of race)   10   10   16   36 
Region of Enrollment 
[Units: Participants]
Count of Participants
       
United States         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
United States   6   8   7   21 
Brazil         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
Brazil   9   9   11   29 
Tanner stage [1] 
[Units: Participants]
Count of Participants
       
       
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
 1   0   2   3 
       
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
 3   2   2   7 
       
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
 5   1   2   8 
       
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
 1   8   6   15 
       
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
 5   6   6   17 
[1] Tanner stage represents the extent of physical development in children, adolescents and adults. It is based on external physical characteristics such as the size of breasts, genitals and pubic hair. Before puberty children are Tanner 1. Adults are Tanner 5. Study participants were classified as the most advanced stage of breasts and pubic hair (females) and genitals and pubic hair (males).
Smoker 
[Units: Participants]
Count of Participants
       
Yes         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
Yes   0   2   1   3 
No         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
No   15   15   17   47 
Bone age [1] 
[Units: Years]
Median (Full Range)
       
Participants Analyzed 
[Units: Participants]
 15   16   18   49 
   14 
 (10 to 22) 
 16 
 (11 to 23) 
 15 
 (11 to 21) 
 15 
 (10 to 23) 
[1] Bone age estimates maturity of a child's skeletal system. It was assessed by taking an X-ray of the left wrist, hand, and fingers. the X-ray was compared with images in a standard atlas of bone development, based on data from large numbers of other kids of the same gender and age. One participant did not have bone age measured at entry.
Use of tenofovir [1] 
[Units: Participants]
Count of Participants
       
Yes         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
Yes   7   7   9   23 
No         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
No   8   10   9   27 
[1] Tenofovir disoproxil is a drug used to treat HIV
CDC HIV disease category [1] 
[Units: Participants]
Count of Participants
       
A/1         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
A/1   0   1   3   4 
B/2         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
B/2   2   0   6   8 
C/3         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
C/3   13   16   9   38 
[1] Severity of HIV disease was classified using the Centers for Disease Control (CDC) 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults (https://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm). Disease category C/3 is the most advanced.
HIV-1 RNA (copies/ml) 
[Units: Participants]
Count of Participants
       
<= 400         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
<= 400   10   16   15   41 
>400         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
>400   5   1   3   9 
CD4 cell count (cells/mm^3) 
[Units: Participants]
Count of Participants
       
200 - <500         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
200 - <500   3   3   2   8 
500 - < 1000         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
500 - < 1000   10   10   10   30 
>= 1000         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
>= 1000   2   4   6   12 
25-OH Vitamin D (ng/mL) 
[Units: Participants]
Count of Participants
       
10 - < 20         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
10 - < 20   1   5   0   6 
20 - < 30         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
20 - < 30   7   8   6   21 
>= 30         
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
>= 30   7   4   12   23 
Lumbar spine BMD (g/cm^2) 
[Units: G/cm^2]
Median (Full Range)
       
Participants Analyzed 
[Units: Participants]
 15   17   18   50 
   0.64 
 (0.47 to 0.93) 
 0.73 
 (0.50 to 0.89) 
 0.66 
 (0.50 to 0.88) 
 0.70 
 (0.47 to 0.93) 
Whole body (with head) BMD (g/cm^2) [1] 
[Units: G/cm^2]
Median (Full Range)
       
Participants Analyzed 
[Units: Participants]
 14   16   16   46 
   0.87 
 (0.68 to 1.05) 
 0.91 
 (0.62 to 1.08) 
 0.86 
 (0.69 to 1.08) 
 0.87 
 (0.62 to 1.08) 
[1] Whole body (with head) BMD was missing at entry for some participants because of software problems with the DXA machines.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percent Change From Baseline to Weeks 24 and 48 in Lumbar Spine BMD   [ Time Frame: Weeks 0, 24 and 48 ]

2.  Primary:   Percentage of Participants Developing New Signs, Symptoms, Hematology or Chemistry Laboratory Values Greater Than or Equal to Grade 3 or New Cases of Jaw Osteonecrosis, Atrial Fibrillation, or Non-healing Fractures   [ Time Frame: Week 0 to 48 ]

3.  Secondary:   Percent Change From Baseline to Weeks 24 and 48 in Whole Body (With Head) BMD   [ Time Frame: Weeks 0, 24 and 48 ]

4.  Secondary:   Effect of Other Known Bone Mineral Determinants (Age, Gender, Race/Ethnicity, Steroid Use, Depo-Provera, Tenofovir, Pubertal Stage, Bone Age, Vitamin D Status) and Inflammatory Cytokine Levels on Changes in Lumbar Spine BMD   [ Time Frame: Weeks 0, 24 and 48 ]

5.  Secondary:   Effect of Other Known Bone Mineral Determinants (Age, Gender, Race/Ethnicity, Steroid Use, Depo-Provera, Tenofovir, Pubertal Stage, Bone Age, Vitamin D Status) and Inflammatory Cytokine Levels on Changes in Whole Body (With Head) BMD.   [ Time Frame: Weeks 0, 24 and 48 ]

6.  Secondary:   Change From Baseline to Week 48 in Bone Marker Turnover   [ Time Frame: Weeks 0 and 48 ]

7.  Secondary:   Correlation of Changes in Bone Marker Turnover With Changes in Lumbar Spine and Whole Body (With Head) BMD   [ Time Frame: Weeks 0 and 48 ]

8.  Secondary:   Change From Baseline to Week 48 in Receptor Activator of Nuclear Factor Kappa-B Ligand/Osteoprotegerin (RANKL/OPG) Ratio   [ Time Frame: Weeks 0 and 48 ]

9.  Secondary:   Correlation of Changes in RANKL/OPG Ratio With Changes in Lumbar Spine and Whole Body (With Head) BMD   [ Time Frame: Weeks 0 and 48 ]

10.  Secondary:   Change From Baseline to Week 48 in Central Fat Content   [ Time Frame: Weeks 0 and 48 ]

11.  Secondary:   Correlation of Changes in Central Fat Content With Changes in Lumbar Spine and Whole Body (With Head) BMD   [ Time Frame: Weeks 0 and 48 ]

12.  Secondary:   Percent of Participants With HIV-1 RNA <= 400 Copies/ml   [ Time Frame: Weeks 0, 48, 96 and 144 ]

13.  Secondary:   Change in CD4 Percent From Baseline   [ Time Frame: Weeks 0, 48, 96 and 144 ]

14.  Secondary:   Change in Centers for Disease Control (CDC) HIV Disease Category   [ Time Frame: Weeks 0, 48, 96 and 144 ]

15.  Secondary:   Percent of Participants With Detectable Urinary Alendronate   [ Time Frame: Weeks 48, 96 and 144 ]

16.  Secondary:   Percent Change From Baseline to Week 96 in Lumbar Spine BMD   [ Time Frame: Weeks 0 and 96 ]
Results not yet reported.   Anticipated Reporting Date:   09/2017  

17.  Secondary:   Percent Change From Baseline to Week 96 in Whole Body (With Head) BMD   [ Time Frame: Weeks 0 and 96 ]
Results not yet reported.   Anticipated Reporting Date:   09/2017  

18.  Secondary:   Safety as Measured by the Incidence of New Signs, Symptoms, Hematology or Chemistry Laboratory Values Greater Than or Equal to Grade 3 or New Cases of Jaw Osteonecrosis, Atrial Fibrillation, or Non-healing Fractures   [ Time Frame: Weeks 0 to 96 ]
Results not yet reported.   Anticipated Reporting Date:   09/2017  

19.  Secondary:   Percent Change From Week 48 to Week 96 (Group 1B), Week 48 to Week 144 (Group 1B), and Week 96 to 144 (Group 2) in Lumbar Spine BMD   [ Time Frame: Weeks 48, 96 and 144 ]
Results not yet reported.   Anticipated Reporting Date:   09/2017  

20.  Secondary:   Percent Change From Week 48 to Week 96 (Group 1B), Week 48 to Week 144 (Group 1B), and Week 96 to 144 (Group 2) in Whole Body (With Head) BMD   [ Time Frame: Weeks 48, 96 and 144 ]
Results not yet reported.   Anticipated Reporting Date:   09/2017  


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Melissa Allen, Director, IMPAACT Operations Center
Organization: Family Health International (FHI 360)
phone: (919) 405-1429
e-mail: mallen@fhi360.org


Publications:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00921557     History of Changes
Other Study ID Numbers: P1076
10669 ( Registry Identifier: DAIDS-ES Registry Number )
IMPAACT P1076
Study First Received: June 12, 2009
Results First Received: December 15, 2016
Last Updated: February 8, 2017