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

2021年11月3日 更新者：National Institute of Allergy and Infectious Diseases (NIAID)

Impact of Oral Alendronate Therapy on Bone Mineral Density in HIV-infected Children and Adolescents With Low Bone Mineral Density

HIV-infected children, youth, and adults have lower bone mineral density (BMD) than would be expected for HIV-uninfected people of similar age, weight and race. As the majority of perinatally HIV-infected U.S. children are entering or in adolescence, the potential for HIV-related impaired BMD during the adolescent peak of bone mass acquisition is of particular concern. The primary purpose of this study was to compare changes from pre-treatment levels of BMD of the lumbar spine after 24 and 48 weeks of alendronate treatment with placebo in HIV-infected children and adolescents.

調査の概要

状態

完了

条件

介入・治療

詳細な説明

Puberty is a time when the foundation is laid for healthy bone mass. Over the course of puberty, 26% of bone mass is established in the 4-year period of peak height velocity and up to 60% of adult peak bone mass is established. Factors that affect normal bone mineralization include calcium intake, vitamin D status, degree of physical and weight bearing activities, hormones, genetics, body weight, and general health and nutrition status. HIV-infected children, youth, and adults have lower bone mineral density (BMD) than would be expected for healthy people of similar age, weight, and race. As the majority of perinatally HIV-infected U.S. children are entering or in adolescence, the potential for HIV-related impaired BMD during the adolescent peak of bone mass acquisition is of particular concern. The purpose of this study was to compare changes in BMD of the lumbar spine from pre-treatment levels to 24 and 48 weeks after alendronate treatment or placebo in HIV-infected children and adolescents.

Participants were randomized equally into one of three groups: Group 1A received alendronate for 96 weeks; Group 1B received alendronate for 48 weeks followed by placebo for 48 weeks; Group 2 received placebo for 48 weeks followed by alendronate for 48 weeks. All three groups were followed off treatment for an additional 48 weeks. Participants also received vitamin D/calcium for the duration of the study and were asked to perform 60 minutes of weight-bearing exercise each day.

Clinic visits were scheduled every 12 weeks after entry, with telephone contact visits one, four, and 28 weeks after entry and the week 48 visit. A physical exam and dental assessment was conducted at each clinic visit, and a history of adverse events collected. Dual Energy X-ray absorptiometry (DXA), hematology and chemistry panels were conducted at entry and weeks 24, 48, 72, 96 and 144. Lumbar spine and whole body (with head) BMD was measured using Hologic DXA scanners (QDR4500A, QDR4500W or Delphi A models).

The primary analysis compared changes from entry to 24 and 48 weeks in lumbar spine BMD between Groups 1A and 1B combined (both on alendronate for initial 48 weeks) vs. Group 2 (on placebo for 48 weeks). Study participants were unblinded after 96 weeks of follow-up (the primary completion date) but remained on study, off study treatment, for an additional 48 weeks.

Secondary laboratory outcomes listed in the protocol (bone marker turnover and Receptor Activator of Nuclear Factor Kappa-B Ligand/Osteoprotegerin (RANKL/OPG) Ratio) and central fat content, which required application for additional funding for laboratory testing, will not be performed and no results will be available.

研究の種類

介入

入学 (実際)

52

段階

  • フェーズ2

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

  • アメリカ
    • California
      • Los Angeles、California、アメリカ、90095-1752
        • David Geffen School of Medicine at UCLA NICHD CRS
    • Florida
      • Miami、Florida、アメリカ、33136
        • Pediatric Perinatal HIV Clinical Trials Unit CRS
      • Tampa、Florida、アメリカ、33606
        • USF - Tampa NICHD CRS
    • Illinois
      • Chicago、Illinois、アメリカ、60614-3393
        • Lurie Children's Hospital of Chicago (LCH) CRS
    • Maryland
      • Baltimore、Maryland、アメリカ、21287
        • Johns Hopkins Univ. Baltimore NICHD CRS
    • Massachusetts
      • Worcester、Massachusetts、アメリカ、01605
        • WNE Maternal Pediatric Adolescent AIDS CRS
    • Tennessee
      • Memphis、Tennessee、アメリカ、38105
        • St. Jude Children's Research Hospital CRS
  • ブラジル
      • Sao Paulo、ブラジル、14049-900
        • Univ. of Sao Paulo Brazil NICHD CRS
    • Minas Gerais
      • Belo Horizonte、Minas Gerais、ブラジル、30130-100
        • SOM Federal University Minas Gerais Brazil NICHD CRS
  • プエルトリコ
      • San Juan、プエルトリコ、00936
        • San Juan City Hosp. PR NICHD CRS

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

11年～24年 (子、大人)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

Inclusion Criteria (Version 2.0 of protocol):

  • Documentation of HIV-1 infection
  • HIV-infection acquired before puberty
  • For participants receiving antiretroviral therapy, must have been on the same antiretroviral agents for at least 12 weeks prior to study entry and have a viral load less than 10,000 copies/mL. For participants not receiving antiretroviral therapy, must have not been on antiretroviral agents for at least 12 weeks prior to study entry and have no indication for therapy
  • Lumbar spine DXA BMD z-score less than -1.5 or history of fragility fracture within the prior 12 months (regardless of DXA result).
  • Available for routine dental exam and care every 6 months
  • Demonstrated ability and willingness to swallow study medications
  • Females of reproductive potential must have had a negative pregnancy test at screening and within 48 hours prior to study entry. They must also have agreed to avoid pregnancy while on the study and if engaging in sexual activity, use at least two forms of contraception.
  • Parent or legal guardian able and willing to provide signed informed consent for children who could not provide consent for themselves.

Exclusion Criteria (Version 2.0 of protocol):

  • Body weight more than 300 lbs.
  • For female participants: if on Depo-Provera, they must have been on it for at least 1 year prior to study entry; if not on Depa-Provera, they must have not been on it for at least 1 year prior to study entry.
  • Anticonvulsant therapy
  • Proven growth hormone deficiency
  • Use of growth hormone in the 12 months prior to entry
  • Primary hyperparathyroidism
  • Hypoparathyroidism
  • Renal failure
  • Cushing syndrome
  • Active dental infection
  • Dental or periodontal disease expected to require more than basic restorative care
  • Pregnancy or lactation
  • Esophageal or gastric ulcer, chronic nonsteroidal anti-inflammatory drug (NSAID) use, or aspirin use
  • Tenofovir disoproxil fumarate (TDF): if on TDF, they must have been on it for at least 6 months prior to study entry; if not on TDF, they must have not been on it for at least 6 months prior to study entry.
  • Hemoglobin less than 10 g/dL
  • Any past pharmacologic treatment (except vitamin D and/or calcium supplementation) for low bone density
  • Inability to stand or sit upright for at least 30 minutes
  • Hypersensitivity to any component of alendronate
  • Hypocalcemia (less than the lower limit of normal established by the local laboratory in which it was performed)
  • Known abnormalities of the esophagus that delay esophageal emptying such as stricture or achalasia
  • 25-OH vitamin D less than 10 ng/mL in combination with elevated intact PTH above the upper limit of normal for the local laboratory in which it was performed

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：ランダム化
  • 介入モデル：クロスオーバー割り当て
  • マスキング：ダブル

武器と介入

参加者グループ / アーム
介入・治療
実験的：1A: Alendronate/Alendronate
Participants received alendronate for 96 weeks and calcium carbonate/vitamin D for 144 weeks
薬：Alendronate
Oral tablet taken once weekly: 70 mg if participant greater than 30 kg or 35 mg if participant less than or equal to 30 kg
他の名前：
  • フォサマックス
ダイエットサプリメント：Calcium carbonate/vitamin D
Tablet taken once or twice daily: calcium carbonate (600 mg) and vitamin D (400 IU) once daily for participants with 25-OH-vitamin D levels greater than or equal to 20 ng/mL or twice daily for those with 25-OH-vitamin D levels less than 20 ng/mL
実験的：1B: Alendronate/Placebo
Participants received alendronate for 48 weeks followed by placebo for 48 weeks and calcium carbonate/vitamin D for 144 weeks
薬：Alendronate
Oral tablet taken once weekly: 70 mg if participant greater than 30 kg or 35 mg if participant less than or equal to 30 kg
他の名前：
  • フォサマックス
ダイエットサプリメント：Calcium carbonate/vitamin D
Tablet taken once or twice daily: calcium carbonate (600 mg) and vitamin D (400 IU) once daily for participants with 25-OH-vitamin D levels greater than or equal to 20 ng/mL or twice daily for those with 25-OH-vitamin D levels less than 20 ng/mL
薬：Placebo
Oral tablet taken once weekly
実験的：2: Placebo/Alendronate
Participants received placebo for 48 weeks followed by alendronate for 48 weeks and calcium carbonate/vitamin D for 144 weeks
薬：Alendronate
Oral tablet taken once weekly: 70 mg if participant greater than 30 kg or 35 mg if participant less than or equal to 30 kg
他の名前：
  • フォサマックス
ダイエットサプリメント：Calcium carbonate/vitamin D
Tablet taken once or twice daily: calcium carbonate (600 mg) and vitamin D (400 IU) once daily for participants with 25-OH-vitamin D levels greater than or equal to 20 ng/mL or twice daily for those with 25-OH-vitamin D levels less than 20 ng/mL
薬：Placebo
Oral tablet taken once weekly

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Percent Change From Baseline to Weeks 24 and 48 in Lumbar Spine BMD
時間枠：Weeks 0, 24 and 48
Percent change was calculated as (measurement at time T - measurement at baseline)/measurement at baseline * 100%. Results for Groups 1A and 1B combined as both were on alendronate for the first 48 weeks.
Weeks 0, 24 and 48
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
時間枠：Week 0 to 48
Signs, symptoms, and laboratory values were graded using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0 (December 2004). Results for Groups 1A and 1B were combined as both were on alendronate for the first 48 weeks.
Week 0 to 48

二次結果の測定

結果測定
メジャーの説明
時間枠
Percent Change From Baseline to Weeks 24 and 48 in Whole Body (With Head) BMD
時間枠：Weeks 0, 24 and 48
Percent change was calculated as (measurement at time T - measurement at baseline)/measurement at baseline * 100%. Results for Groups 1A and 1B were combined as both were on alendronate for the first 48 weeks.
Weeks 0, 24 and 48
Percent Change From Baseline to Week 96 in Lumbar Spine BMD
時間枠：Weeks 0 and 96
Percent change was calculated as (measurement at week 96 - measurement at baseline)/measurement at baseline * 100%. Includes Groups 1A and 1B only.
Weeks 0 and 96
Percent Change From Baseline to Week 96 in Whole Body (With Head) BMD
時間枠：Weeks 0 and 96
Percent change was calculated as (measurement at week 96 - measurement at baseline)/measurement at baseline * 100%. Includes Groups 1A and 1B only.
Weeks 0 and 96
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
時間枠：Weeks 0 to 144
Signs, symptoms, and laboratory values were graded using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0 (December 2004).
Weeks 0 to 144
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
時間枠：Weeks 0, 24 and 48
A slope was fit for each participant to their percent change [(measurement at time T - measurement at baseline)/measurement at baseline)*100%] in lumbar spine BMD from baseline. Results represent average changes in lumbar spine BMD over one year. Results are summarized for age, gender, ethnicity, tenofovir use, Tanner stage, bone age and vitamin D level. Only one participant was on steroids and none were using Dep-Provera. Inflammatory cytokine levels were not assayed. Results were combined for Groups 1A and 1B as both were on alendronate for the first 48 weeks.
Weeks 0, 24 and 48
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.
時間枠：Weeks 0, 24 and 48
A slope was fit for each participant to their percent change [(measurement at time T - measurement at baseline)/measurement at baseline)*100%] in whole body (with head) BMD from baseline. Results represent average changes in whole body (with head) BMD over one year. Results are summarized for age, gender, ethnicity, tenofovir use, Tanner stage, bone age and vitamin D level. Only one participant was on steroids and none were using Dep-Provera. Inflammatory cytokine levels were not assayed. Results were combined for Groups 1A and 1B as both were on alendronate for the first 48 weeks.
Weeks 0, 24 and 48
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
時間枠：Weeks 48, 96 and 144
Percent change was calculated as (measurement at time T2 - measurement at time T1)/measurement at Time T1 * 100%.
Weeks 48, 96 and 144
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
時間枠：Weeks 48, 96 and 144
Percent change was calculated as (measurement at time T2 - measurement at time T2)/measurement at time T1 * 100%.
Weeks 48, 96 and 144
Change From Baseline to Week 48 in Bone Marker Turnover
時間枠：Weeks 0 and 48
Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Weeks 0 and 48
Correlation of Changes in Bone Marker Turnover With Changes in Lumbar Spine and Whole Body (With Head) BMD
時間枠：Weeks 0 and 48
Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Weeks 0 and 48
Change From Baseline to Week 48 in Receptor Activator of Nuclear Factor Kappa-B Ligand/Osteoprotegerin (RANKL/OPG) Ratio
時間枠：Weeks 0 and 48
Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Weeks 0 and 48
Correlation of Changes in RANKL/OPG Ratio With Changes in Lumbar Spine and Whole Body (With Head) BMD
時間枠：Weeks 0 and 48
Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Weeks 0 and 48
Change From Baseline to Week 48 in Central Fat Content
時間枠：Weeks 0 and 48
Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Weeks 0 and 48
Correlation of Changes in Central Fat Content With Changes in Lumbar Spine and Whole Body (With Head) BMD
時間枠：Weeks 0 and 48
Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Weeks 0 and 48
Percent of Participants With HIV-1 RNA <= 400 Copies/ml
時間枠：Weeks 0, 48, 96 and 144
Percent calculated as number of participants with HIV-1 RNA <= 400 copies/ml relative to the number of participants with HIV-1 RNA measured at that time point.
Weeks 0, 48, 96 and 144
Change in CD4 Percent From Baseline
時間枠：Weeks 0, 48, 96 and 144
Change in percentage of lymphocytes that are CD4 cells calculated as measurement at each time point minus baseline measurement
Weeks 0, 48, 96 and 144
Change in Centers for Disease Control (CDC) HIV Disease Category
時間枠：Weeks 144
Percentage of participants advancing in CDC HIV disease category from baseline throughout study follow-up
Weeks 144
Percent of Participants With Detectable Urinary Alendronate
時間枠：Weeks 48, 96 and 144
Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Weeks 48, 96 and 144

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

National Institute of Allergy and Infectious Diseases (NIAID)

協力者

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

捜査官

  • スタディチェア：George K. Siberry, MD、Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

出版物と役立つリンク

研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。

一般刊行物

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2009年11月1日

一次修了 (実際)

2016年1月1日

研究の完了 (実際)

2017年1月1日

試験登録日

最初に提出

2009年6月12日

QC基準を満たした最初の提出物

2009年6月12日

最初の投稿 (見積もり)

2009年6月16日

学習記録の更新

投稿された最後の更新 (実際)

2021年11月5日

QC基準を満たした最後の更新が送信されました

2021年11月3日

最終確認日

2017年6月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • P1076
  • 10669 (その他の識別子：Fred Hutch/University of Washington Cancer Consortium)
  • IMPAACT P1076

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

いいえ

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

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