Effect of Multiple Micronutrient Supplementation on Growth, Morbidity, and Mortality of HIV Infected Children in Uganda (MMS)

• ClinicalTrials.gov Identifier: NCT00122941
• Recruitment Status: Completed
• First Posted: July 22, 2005
• Last Update Posted: June 16, 2008
• Sponsor: Makerere University
• Collaborator: The Norwegian Programme for Development, Research and Higher Education
• Information provided by: Makerere University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HIV Infections	Dietary Supplement: multiple micronutrients	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 860 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• 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 Start Date: June 2005
• Actual Primary Completion Date: May 2008
• Actual Study Completion Date: May 2008

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Number of children dying during the study period
2. Average weight gain in each of the treatment groups

Secondary Outcome Measures :

1. Blood micronutrient levels
2. Incidence/prevalence of diarrhoea
3. HIV disease progression (CD4 count and clinical staging)
4. Prevalence of C. parvum and E. bieneusi
5. Adverse events related to supplementation

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 5 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Norway

Centre for International Health University of Bergen

Bergen, Norway, NO-5021

Uganda

Department of Paediatrics and Child Health, Mulago Hospital

Kampala, Uganda, P.O. 7072

Sponsors and Collaborators

Makerere University

The Norwegian Programme for Development, Research and Higher Education

Investigators

• Principal Investigator: Grace Ndeezi, MMed; Makerere University, Medical School, Department of Paediatrics and Child Health

More Information

Publications:

Jiamton S, Pepin J, Suttent R, Filteau S, Mahakkanukrauh B, Hanshaoworakul W, Chaisilwattana P, Suthipinittharm P, Shetty P, Jaffar S. A randomized trial of the impact of multiple micronutrient supplementation on mortality among HIV-infected individuals living in Bangkok. AIDS. 2003 Nov 21;17(17):2461-9. doi: 10.1097/00002030-200311210-00008.

Kelly P, Musonda R, Kafwembe E, Kaetano L, Keane E, Farthing M. Micronutrient supplementation in the AIDS diarrhoea-wasting syndrome in Zambia: a randomized controlled trial. AIDS. 1999 Mar 11;13(4):495-500. doi: 10.1097/00002030-199903110-00008.

Bhutta ZA, Black RE, Brown KH, Gardner JM, Gore S, Hidayat A, Khatun F, Martorell R, Ninh NX, Penny ME, Rosado JL, Roy SK, Ruel M, Sazawal S, Shankar A. Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators' Collaborative Group. J Pediatr. 1999 Dec;135(6):689-97. doi: 10.1016/s0022-3476(99)70086-7.

Campa A, Shor-Posner G, Indacochea F, Zhang G, Lai H, Asthana D, Scott GB, Baum MK. Mortality risk in selenium-deficient HIV-positive children. J Acquir Immune Defic Syndr Hum Retrovirol. 1999 Apr 15;20(5):508-13. doi: 10.1097/00042560-199904150-00015.

Tang AM, Graham NM, Semba RD, Saah AJ. Association between serum vitamin A and E levels and HIV-1 disease progression. AIDS. 1997 Apr;11(5):613-20. doi: 10.1097/00002030-199705000-00009.

Allard JP, Aghdassi E, Chau J, Tam C, Kovacs CM, Salit IE, Walmsley SL. Effects of vitamin E and C supplementation on oxidative stress and viral load in HIV-infected subjects. AIDS. 1998 Sep 10;12(13):1653-9. doi: 10.1097/00002030-199813000-00013.

Fawzi W, Msamanga G, Spiegelman D, Hunter DJ. Studies of vitamins and minerals and HIV transmission and disease progression. J Nutr. 2005 Apr;135(4):938-44. doi: 10.1093/jn/135.4.938.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

• Responsible Party: James K Tumwine, Makerere University Medical School
• ClinicalTrials.gov Identifier: NCT00122941
• Other Study ID Numbers: 2002/HD11/2078/MMS; MV910
• First Posted: July 22, 2005
• Last Update Posted: June 16, 2008
• Last Verified: June 2008

Keywords provided by Makerere University:

multiple; micronutrients; supplementation; HIV; children; randomised; trial; mortality; morbidity; growth; Uganda

Additional relevant MeSH terms:

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Micronutrients; Trace Elements; Physiological Effects of Drugs