MalariaPhase 3MACHNCT00623857
Micronutrients and Child Health Study
A Phase 3 study testing Zinc, Vitamins and minerals other than zinc and Vitamins plus zinc and other minerals in people with Malaria, run by Wageningen University at 1 site in Tanzania.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 60 monthsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- Zinc, Vitamins and minerals other than zinc and Vitamins plus zinc and other minerals
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 612 participants
- Where
- 1 siteTanzania
- Study dates
- Mar 2008to Mar 2009
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 60 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Supplementation With Zinc and Other Micronutrients on the Health and Development of African Children
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.
Read the 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.
- Conditions
- Malaria
- Being tested
- Zinc, Vitamins and minerals other than zinc, Vitamins plus zinc and other minerals, Placebo
- 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
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZincDietary supplement
Daily oral supplementation with zinc, 10 mg, for an average of 60 weeks
Vitamins and minerals other than zincDietary supplement
Daily supplementation with 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 and calcium; for an average of 60 weeks
Vitamins plus zinc and other mineralsDietary supplement
Daily oral supplementation with zinc, 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 and calcium; for an average of 60 weeks
PlaceboDietary supplement
Daily oral supplementation with placebo for vitamins and all minerals; for an average of 60 weeks
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Zinc Receives: Dietary Supplement: Zinc |
| 2 | Active comparator | Vitamins and minerals other than zinc Receives: Dietary Supplement: Vitamins and minerals other than zinc |
| 3 | Active comparator | Vitamins plus zinc and other minerals Receives: Dietary Supplement: Vitamins plus zinc and other minerals |
| 4 | Placebo comparator | Placebo for all vitamins and minerals Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Febrile malaria episodes
Measured: 60 weeks
Secondary outcomes (4)
Haematologic and urinary indicators of micronutrient status
Measured: 30 weeks after start of intervention
Anthropometric indices
Measured: 57 weeks after start of intervention
T cell immune responses to in vitro stimulation with a crude Plasmodium falciparum lysate
Measured: 30 weeks after start of intervention
Plasma immunoglobulin concentrations
Measured: 2 weeks after malaria episodes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2008 (estimated)
- Study startMar 2008
- Primary completionMar 2009
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 612 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wageningen University
- Sponsor type
- University, hospital or other
- Collaborators
- Kilimanjaro Christian Medical Centre, Tanzania
- Responsible party
- Sponsor
- Investigators
- Hans Verhoef, PhD, Principal investigator, Wageningen University, Cell Biology and Immunology GroupRaimos M Olomi, MD MMed MPH, Study chair, Kilimanjaro Christian Medical CentreHuub FJ Savelkoul, PhD, Study director, Wageningen University, Cell Biology and Immunology GroupJohn F. Shao, MD, Study director, Kilimanjaro Christian Medical Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00623857
- Sponsor's protocol ID
- WAO 93-442
- Acronym
- MACH
- Status last verified
- Nov 2014
- First submitted
- 14 Feb 2008
- Last updated
- 17 Nov 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 25344520Pasricha 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.
PubMed 24807559Hendriksen 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.
PubMed 23136222Veenemans 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.
PubMed 22870238Veenemans 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.
PubMed 22131908Veenemans 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.
PubMed 21939508Veenemans 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.
PubMed 21666789Mbugi 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.
PubMed 20546583Mbugi 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.
PubMed 20470442Veenemans 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.
PubMed 18582194
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Supplementation With Zinc and Other Micronutrients on the Health and Development of African Children
- ClinicalTrials.gov ID
- NCT00623857
- Acronym / sponsor ID
- MACH / WAO 93-442
- Conditions
- Malaria
- Keywords
- Micronutrients, Zinc, Vitamins, Trace elements, Minerals, Vitamin A, Vitamin B1, Vitamin B2
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 612 participants (actual)
- Lead sponsor
- Wageningen UniversityUniversity, hospital or other
- Collaborators
- Kilimanjaro Christian Medical Centre, Tanzania
- Study start
- Mar 2008
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 26 Feb 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Dietary Supplement: ZincZinc |
| 2 | Active comparator | Dietary Supplement: Vitamins and minerals other than zincVitamins and minerals other than zinc |
| 3 | Active comparator | Dietary Supplement: Vitamins plus zinc and other mineralsVitamins plus zinc and other minerals |
| 4 | Placebo comparator | Dietary Supplement: PlaceboPlacebo for all vitamins and minerals |
Who may qualify
- Ages
- 6 to 60 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZincDaily oral supplementation with zinc, 10 mg, for an average of 60 weeks | Dietary supplement | 1 |
| Vitamins and minerals other than zincDaily supplementation with 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 and calcium; for an average of 60 weeks | Dietary supplement | 2 |
| Vitamins plus zinc and other mineralsDaily oral supplementation with zinc, 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 and calcium; for an average of 60 weeks | Dietary supplement | 3 |
| PlaceboDaily oral supplementation with placebo for vitamins and all minerals; for an average of 60 weeks | Dietary supplement | 4 |
Primary outcome
Febrile malaria episodes
Time frame: 60 weeks
4 secondary outcomes
Haematologic and urinary indicators of micronutrient status
Time frame: 30 weeks after start of intervention
Anthropometric indices
Time frame: 57 weeks after start of intervention
T cell immune responses to in vitro stimulation with a crude Plasmodium falciparum lysate
Time frame: 30 weeks after start of intervention
Plasma immunoglobulin concentrations
Time frame: 2 weeks after malaria episodes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2014.
- Results publication: PubMed 25344520Imwong 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.
- Results publication: PubMed 24807559Pasricha 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.
- Results publication: PubMed 23136222Hendriksen 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.
- Results publication: PubMed 22870238Veenemans 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.
- Results publication: PubMed 22131908Veenemans 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.
- Results publication: PubMed 21939508Veenemans 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.
- Results publication: PubMed 21666789Veenemans 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.
- Results publication: PubMed 20546583Mbugi 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.
- Results publication: PubMed 20470442Mbugi 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.
- Results publication: PubMed 18582194Veenemans 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hans Verhoef, PhD principal investigator
Wageningen University, Cell Biology and Immunology Group
Raimos M Olomi, MD MMed MPH study chair
Kilimanjaro Christian Medical Centre
Huub FJ Savelkoul, PhD study director
Wageningen University, Cell Biology and Immunology Group
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Zinc, Vitamins and minerals other than zinc and Vitamins plus zinc and other minerals in people with Malaria, run by Wageningen University at 1 site in Tanzania.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Tanzania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Febrile malaria episodes (time frame: 60 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00623857, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Nov 2014.