Clinical trial NCT00122941: Effect of Multiple Micronutrient Supplementation on Growth, Morbidity, and Mortality of HIV Infected Children in Uganda
Official title: Effect of Multiple Micronutrient Supplementation on Growth, Morbidity, and Mortality of HIV Infected Children in Uganda: a Randomised Double Blind Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: multiple
micronutrients
supplementation
HIV
children
randomised
trial
mortality
morbidity
growth
Uganda
Lead sponsor: Makerere University
Sponsor class: OTHER
Collaborators: name: The Norwegian Programme for Development, Research and Higher Education
First posted: 2005-07-22
Enrollment: 860
Sex: ALL
Minimum age (years): 1
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Micronutrient deficiencies are common in HIV infected children and are aggravated by poor nutrition, especially in poor resource countries such as Uganda. It appears that micronutrient deficiencies contribute to immune dysfunction, increased morbidity and HIV disease progression. Hitherto, there has been no randomised controlled trial to assess the effect of multiple micronutrient supplementation on morbidity and mortality in HIV infected children in Africa. Therefore, the investigators shall carry out a randomised controlled trial to determine the effect of multiple micronutrient supplementation on morbidity, weight gain and mortality among HIV infected children aged 1 to 5 years in Uganda.

Hypothesis: Daily administration of twice the recommended dietary allowance (2RDA) of multiple micronutrients to HIV infected children aged one to five years, for 6 months, will reduce all cause mortality from 24% to 14.4% in one year and result in a weight gain difference of 150 grams.

Detailed description: Micronutrient deficiencies are common in HIV infected children and are aggravated by poor nutrition, especially in poor resource countries such as Uganda. It appears that micronutrient deficiencies contribute to immune dysfunction, increased morbidity and HIV disease progression. Hitherto, there has been no randomised controlled trial to assess the effect of multiple micronutrient supplementation on morbidity and mortality in HIV infected children in Africa. Therefore, the investigators shall carry out a randomised controlled trial to determine the effect of multiple micronutrient supplementation on morbidity, weight gain and mortality among HIV infected children aged 1 to 5 years in Uganda.

Hypothesis: Daily administration of twice the recommended dietary allowance (2RDA) of multiple micronutrients to HIV infected children aged one to five years, for 6 months, will reduce all cause mortality from 24% to 14.4% in one year and result in a weight gain difference of 150 grams.

A sample size of 373 was calculated assuming that the mortality risk in one year in HIV infected children is 24% (Barhane et al) and that this risk will be reduced to 14.4% in the intervention group (40% effect size) with 90% power and 95% confidence.

Assuming a 10% attrition rate (38 study participants), the final sample size in each group is 411.

Eligibility criteria: Inclusion Criteria:

* Aged 1 to 5 years
* HIV infection (previously confirmed by 2 ELISAs for children \> 18 months; DNA PCR for those \< 18 months)
* Informed consent from the parent/caretaker
* Ability to return for follow-up (lives within a radius of 15 km from hospital and unlikely to change residence during the course of the study)

Exclusion Criteria:

* Children already enrolled in other studies
* Children with severe abnormalities which are likely to impair oral intake (for example, severe cerebral palsy)
* Severely ill children requiring urgent admission and resuscitation

Primary outcomes:
measure: Number of children dying during the study period
measure: Average weight gain in each of the treatment groups
Secondary outcomes:
measure: Blood micronutrient levels
measure: Incidence/prevalence of diarrhoea
measure: HIV disease progression (CD4 count and clinical staging)
measure: Prevalence of C. parvum and E. bieneusi
measure: Adverse events related to supplementation
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Centre for International Health University of Bergen
city: Kampala
country: Uganda
facility: Department of Paediatrics and Child Health, Mulago Hospital
Study officials:
affiliation: Makerere University, Medical School, Department of Paediatrics and Child Health
name: Grace Ndeezi, MMed
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Ndeezi G, Tumwine JK, Ndugwa CM, Bolann BJ, Tylleskar T. Multiple micronutrient supplementation improves vitamin B(1)(2) and folate concentrations of HIV infected children in Uganda: a randomized controlled trial. Nutr J. 2011 May 21;10:56. doi: 10.1186/1475-2891-10-56.
citation: Ndeezi G, Tumwine JK, Bolann BJ, Ndugwa CM, Tylleskar T. Zinc status in HIV infected Ugandan children aged 1-5 years: a cross sectional baseline survey. BMC Pediatr. 2010 Sep 21;10:68. doi: 10.1186/1471-2431-10-68.
citation: Ndeezi G, Tylleskar T, Ndugwa CM, Tumwine JK. Effect of multiple micronutrient supplementation on survival of HIV-infected children in Uganda: a randomized, controlled trial. J Int AIDS Soc. 2010 Jun 3;13:18. doi: 10.1186/1758-2652-13-18.