Calcium and High-dose Vitamin D Supplementation on Bone Mineral Density Among HIV-infected Children and Adolescents

Study Overview
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Brief Summary
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Since there is no cure for HIV, therefore antiretroviral therapy must be taken life-long. Some of the HIV medications can negatively impact the health of the bone and is even more exacerbated in perinatally HIV-injected children and adolescents because this is the period when the bone peaks. Bone loss during this period can be devastating and increase the risk for developing weak bones later in life. Supplementation of calcium and vitamin D have not been well studied in HIV-infected children and adolescents in developing countries. Therefore it is not clear whether higher doses of these supplementations can thwart the damages or not.

Detailed Description
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Adverse bone health is one of the major long-term complications among perinatally HIV-infected children and adolescents receiving ART. Since a great deal of bone mineral accrual occurs during the adolescent years and the peak attainment is usually seen at age 18 years, the loss of bone deposition during this period could lead to serious consequences, particularly increased risk of osteoporosis and bone fragility in later of life. A previous study demonstrated that prevalence of low BMD among perinatally HIV-infected Thai children and adolescents was high (25%). However, the prevention strategies such as calcium and vitamin D supplementation which are widely recommended by many guidelines for preventing of osteoporosis and bone fracture have not been well studied to prove their effectiveness among HIV-infected children and adolescents, especially in resource-limited countries. This is considered as the critical research question in pediatric HIV/AIDS field which are urgently required robust and in-depth investigations. This randomized clinical trial study will provide important information about the effect of calcium and high dose (comparing to normal dose) vitamin D supplementation on BMD among ART-experienced, perinatally acquired HIV-infected children and adolescents to best understand the relative contributions of the supplementation to improve bone health status. This study will address research questions, fill gaps in knowledge, and draw clinician attentions to the important long-term medical complications in children and adolescents who are growing up with HIV. Moreover, this study will inform healthcare providers and policy makers about the importance of calcium and vitamin D supplementation as one of the measurement to prevent long-term deterioration of bone mass and the mean to promote bone health among these populations. The funding for this study is the National Research University, Chiang Mai University.

Official Title
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Effect of Calcium and High-dose Vitamin D Supplementation on Bone Mineral Density Among Perinatally HIV-infected Children and Adolescents

Conditions
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Adverse Bone Health, HIV Infection

Intervention / Treatment
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* Dietary Supplement: High dose vitamin D and calcium
* Dietary Supplement: Normal dose vitamin D and calcium


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Participants age 10-20 years. Have a history and/or medical record of HIV infection. Have a history and/or medical record and/or maternal HIV status confirmed of perinatally acquired HIV infection. Have virological suppression after receiving ART, defined as plasma HIV RNA less than 400 copies/mL within 12 months prior to screening. Participants who had been evaluated for BMD (have BMD result) within 1 year prior to entry visit. Caregivers and/or participants gives written inform consent/assent form. Exclusion criteria: Participants who have a documented history of bone fracture at any time prior to screening. Participants who have received any form of calcium greater than 1000 mg/day of elemental calcium at least once within 6 months prior screening. Participants who have received any form of vitamin D (e.g., ergocalciferol or cholecalciferol) supplementation greater than 400 IU/day at least once within 6 months prior to screening. Participants who have received any past pharmacologic treatment for low bone density or osteoporosis (e.g., alendronate) at any time prior to screening. Participants who have a documented history of growth hormone deficiency at any time or using growth hormone within 6 months prior to screening. Participants who have a documented history of primary hyperparathyroidism, hypoparathyroidism, or cushing syndrome at any time prior to screening. Participants who have a documented prior history of kidney stone, renal failure, or renal function impairment (serum creatinine >2 mg/dL). Participants who have a documented prior history of chronic active liver diseases, or liver impairment (alanine aminotransferase [ALT] >100 IU/L at least 2 times within 6 months). Participants who have a documented prior history of thalassemia major (homozygous β-Thalassemia or β-Thalassemia/Hemoglobin E) or sickle cell disease. Participants use any oral, intravenous, or inhaled steroids within 6 months prior to study entry (intranasal steroid use is allowed). Participants who have received anticonvulsant medications (phenytoin, phenobarbital, carbamazepine), methotrexate, within 6 months prior to screening. Pregnancy or breast feeding Participants who have any condition that, in the opinion of the site investigator, would compromise the subject's ability to participate in the study.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High dose vitamin D and calcium<br>Fixed-dose combination (FDC) of 1,500 mg of calcium carbonate (equivalent to 600 mg of elemental calcium) and 200 IU of vitamin D3, administered orally twice daily plus vitamin D2 (20,000 IU/cap) administered once weekly (a total of 1,200 mg of elemental calcium and 3,200 IU of vitamin D daily) | Dietary Supplement: High dose vitamin D and calcium<br>* participants will receive a FDC tablet containing 1500 mg of calcium carbonate (equivalent to 600 mg of elemental calcium) and 200 IU of vitamin D3. This drug will be administered as 1 tablet orally twice daily and is to be taken with food. In addition, participants will receive vitamin D2 capsule containing 20,000 IU of ergocalciferol, which will be administered as 1 capsule orally once weekly at any time (not related with meal).<br>|
| Active Comparator: Normal dose vitamin D and calcium<br>Fixed-dose combination (FDC) of 1,500 mg of calcium carbonate (equivalent to 600 mg of elemental calcium) and 200 IU of vitamin D3, administered orally twice daily (a total of 1,200 mg of elemental calcium and 400 IU of vitamin D daily) | Dietary Supplement: Normal dose vitamin D and calcium<br>* participants will receive a FDC tablet containing 1500 mg of calcium carbonate (equivalent to 600 mg of elemental calcium) and 200 IU of vitamin D3. This drug will be administered as 1 tablet orally twice daily and is to be taken with food<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| lumbar spine Bone Mineral Density (BMD) | To compare the changes in lumbar spine BMD in perinatally HIV-infected children and adolescents receives 48-week of calcium and high-dose vitamin D supplementation with that of children and adolescents receiving 48-week of calcium and normal dose vitamin D supplementation. | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Calcium, Adverse bone health, Bone demineralization, HIV-infection, Children, Adolescents, Vitamin D, Supplementation