Clinical trial NCT02426840: Calcium and High-dose Vitamin D Supplementation on Bone Mineral Density Among HIV-infected Children and Adolescents
Official title: Effect of Calcium and High-dose Vitamin D Supplementation on Bone Mineral Density Among Perinatally HIV-infected Children and Adolescents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Adverse Bone Health
HIV Infection
Keywords: Adverse bone health
Bone demineralization
HIV-infection
Children
Adolescents
Calcium
Vitamin D
Supplementation
Lead sponsor: Chiang Mai University
Sponsor class: OTHER
Collaborators: name: HIV-NAT, Thai Red Cross - AIDS Research Centre
name: Nakornping Hospital
First posted: 2015-04-27
Enrollment: 200
Sex: ALL
Minimum age (years): 10
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: lumbar spine Bone Mineral Density (BMD)
timeFrame: 48 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: HIV-NAT, Thai Red Cross - AIDS Research Centre
city: Bangkok
country: Thailand
facility: Queen Sirikit National Institute of Child Health
city: Chiang Mai
country: Thailand
facility: Faculty of Medicine and Research Institute for Health Sciences (RIHES), Chiang Mai University
city: Chiang Mai
country: Thailand
facility: Nakornping hospital (NKP)
city: Chiang Rai
country: Thailand
facility: Chiangrai Prachanukroh Hospital
Study officials:
affiliation: Chiang Mai University
name: Tavitiya Sudjaritruk, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sudjaritruk T, Bunupuradah T, Aurpibul L, Kanjanavanit S, Chotecharoentanan T, Sricharoen N, Ounchanum P, Suntarattiwong P, Pornpaisalsakul K, Puthanakit T; CAL-D Study Group. Impact of Vitamin D and Calcium Supplementation on Bone Mineral Density and Bone Metabolism Among Thai Adolescents With Perinatally Acquired Human Immunodeficiency Virus (HIV) Infection: A Randomized Clinical Trial. Clin Infect Dis. 2021 Nov 2;73(9):1555-1564. doi: 10.1093/cid/ciab547.