Clinical trial NCT00623857: Micronutrients and Child Health Study
Official title: Effects of Supplementation With Zinc and Other Micronutrients on the Health and Development of African Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malaria
Keywords: Micronutrients
Zinc
Vitamins
Trace elements
Minerals
Vitamin A
Vitamin B1
Vitamin B2
Niacin
Vitamin B6
Folic acid
Vitamin B12
Vitamin C
Vitamin D
Vitamin E
Vitamin K
Iron
Iodine
Copper
Selenium
Magnesium
Calcium
Malaria
Immunity
Anthropometry
Lead sponsor: Wageningen University
Sponsor class: OTHER
Collaborators: name: Kilimanjaro Christian Medical Centre, Tanzania
First posted: 2008-02-26
Enrollment: 612
Sex: ALL
Minimum age (years): 6
Maximum age (years): 60
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine to what extent supplementation with zinc and other micronutrients are efficacious in preventing malaria in young Tanzanian children.

Detailed description: Zinc is essential for the functioning of the immune system. Supplementation trials in Asia, Latin America, the Pacific and developed countries have shown that increasing zinc intake has great potential to control common infections in children, but the response to supplementation may be different in Africa, where the primary environmental challenge to children's health is malaria. Simultaneous supplementation with other potentially limiting nutrients may be required to overcome a lack of response when zinc is given alone. The project aims at measuring effects of daily oral supplementation with zinc and other micronutrients, given either alone or in combination, on malaria incidence and nutritional status, and on indicators of immunity.

Eligibility criteria: Inclusion Criteria:

* Aged 6-60 months
* Permanently residing in the study area
* Being moderately or mildly stunted (height-for-age z-score \<-1.5 SD)
* Informed consent from parents or guardians obtained

Exclusion Criteria:

* Severe wasting (weight-for-height z-score \<-3 SD)
* Hemoglobin concentration \<70 g/L
* Axillary temperature ≥37.50 °C with malaria antigenemia
* Signs and symptoms at randomisation suggesting malaria, hepatitis, HIV/AIDS, tuberculosis, sickle cell disease or other severe condition
* Unable to produce a venous blood sample (\>1 mL)

Primary outcomes:
measure: Febrile malaria episodes
timeFrame: 60 weeks
Secondary outcomes:
measure: Haematologic and urinary indicators of micronutrient status
timeFrame: 30 weeks after start of intervention
measure: Anthropometric indices
timeFrame: 57 weeks after start of intervention
measure: T cell immune responses to in vitro stimulation with a crude Plasmodium falciparum lysate
timeFrame: 30 weeks after start of intervention
measure: Plasma immunoglobulin concentrations
timeFrame: 2 weeks after malaria episodes
Other outcomes:
Locations:
city: Moshi
country: Tanzania
facility: Kilimanjaro Christian Medical Centre
Study officials:
affiliation: Wageningen University, Cell Biology and Immunology Group
name: Hans Verhoef, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kilimanjaro Christian Medical Centre
name: Raimos M Olomi, MD MMed MPH
role: STUDY_CHAIR
affiliation: Wageningen University, Cell Biology and Immunology Group
name: Huub FJ Savelkoul, PhD
role: STUDY_DIRECTOR
affiliation: Kilimanjaro Christian Medical Centre
name: John F. Shao, MD
role: STUDY_DIRECTOR
References:
citation: Imwong M, Woodrow CJ, Hendriksen IC, Veenemans J, Verhoef H, Faiz MA, Mohanty S, Mishra S, Mtove G, Gesase S, Seni A, Chhaganlal KD, Day NP, Dondorp AM, White NJ. Plasma concentration of parasite DNA as a measure of disease severity in falciparum malaria. J Infect Dis. 2015 Apr 1;211(7):1128-33. doi: 10.1093/infdis/jiu590. Epub 2014 Oct 24.
citation: Pasricha SR, Atkinson SH, Armitage AE, Khandwala S, Veenemans J, Cox SE, Eddowes LA, Hayes T, Doherty CP, Demir AY, Tijhaar E, Verhoef H, Prentice AM, Drakesmith H. Expression of the iron hormone hepcidin distinguishes different types of anemia in African children. Sci Transl Med. 2014 May 7;6(235):235re3. doi: 10.1126/scitranslmed.3008249.
citation: Hendriksen IC, White LJ, Veenemans J, Mtove G, Woodrow C, Amos B, Saiwaew S, Gesase S, Nadjm B, Silamut K, Joseph S, Chotivanich K, Day NP, von Seidlein L, Verhoef H, Reyburn H, White NJ, Dondorp AM. Defining falciparum-malaria-attributable severe febrile illness in moderate-to-high transmission settings on the basis of plasma PfHRP2 concentration. J Infect Dis. 2013 Jan 15;207(2):351-61. doi: 10.1093/infdis/jis675. Epub 2012 Nov 7.
citation: Veenemans J, Schouten LR, Ottenhof MJ, Mank TG, Uges DR, Mbugi EV, Demir AY, Kraaijenhagen RJ, Savelkoul HF, Verhoef H. Effect of preventive supplementation with zinc and other micronutrients on non-malarial morbidity in Tanzanian pre-school children: a randomized trial. PLoS One. 2012;7(8):e41630. doi: 10.1371/journal.pone.0041630. Epub 2012 Aug 3.
citation: Veenemans J, Milligan P, Prentice AM, Schouten LR, Inja N, van der Heijden AC, de Boer LC, Jansen EJ, Koopmans AE, Enthoven WT, Kraaijenhagen RJ, Demir AY, Uges DR, Mbugi EV, Savelkoul HF, Verhoef H. Effect of supplementation with zinc and other micronutrients on malaria in Tanzanian children: a randomised trial. PLoS Med. 2011 Nov;8(11):e1001125. doi: 10.1371/journal.pmed.1001125. Epub 2011 Nov 22.
citation: Veenemans J, Jansen EJ, Baidjoe AY, Mbugi EV, Demir AY, Kraaijenhagen RJ, Savelkoul HF, Verhoef H. Effect of alpha(+)-thalassaemia on episodes of fever due to malaria and other causes: a community-based cohort study in Tanzania. Malar J. 2011 Sep 22;10:280. doi: 10.1186/1475-2875-10-280.
citation: Veenemans J, Mank T, Ottenhof M, Baidjoe A, Mbugi EV, Demir AY, Wielders JP, Savelkoul HF, Verhoef H. Protection against diarrhea associated with Giardia intestinalis Is lost with multi-nutrient supplementation: a study in Tanzanian children. PLoS Negl Trop Dis. 2011 Jun;5(6):e1158. doi: 10.1371/journal.pntd.0001158. Epub 2011 Jun 7.
citation: Mbugi EV, Meijerink M, Veenemans J, Jeurink PV, McCall M, Olomi RM, Shao JF, Chilongola JO, Verhoef H, Savelkoul HF. Effect of nutrient deficiencies on in vitro Th1 and Th2 cytokine response of peripheral blood mononuclear cells to Plasmodium falciparum infection. Malar J. 2010 Jun 14;9:162. doi: 10.1186/1475-2875-9-162.
citation: Mbugi EV, Meijerink M, Veenemans J, Jeurink PV, McCall M, Olomi RM, Shao JF, Verhoef H, Savelkoul HF. Alterations in early cytokine-mediated immune responses to Plasmodium falciparum infection in Tanzanian children with mineral element deficiencies: a cross-sectional survey. Malar J. 2010 May 17;9:130. doi: 10.1186/1475-2875-9-130.
citation: Veenemans J, Andang'o PE, Mbugi EV, Kraaijenhagen RJ, Mwaniki DL, Mockenhaupt FP, Roewer S, Olomi RM, Shao JF, van der Meer JW, Savelkoul HF, Verhoef H. Alpha+ -thalassemia protects against anemia associated with asymptomatic malaria: evidence from community-based surveys in Tanzania and Kenya. J Infect Dis. 2008 Aug 1;198(3):401-8. doi: 10.1086/589884.