DiarrheaNCT00272116
Effect of Zinc and Vitamin A Supplementation on Diarrhea, Physical Growth and Immune Response in Malnourished Children
A study testing Zinc and vitamin A single dose at enrollment in people with Diarrhea and Pneumonia, run by Society for Applied Studies at 1 site in India.
Trial summary
Zinc deficiency is common in developing country children, as food intakes are often low, foods from animal sources are infrequently used, the bioavailability of zinc from staple cereal-based diets is limited and zinc losses occur during recurring diarrheal illnesses. Read more about this study
- Who is it for?
- Ages 6 to 30 monthsHealthy volunteers can take part
- Conditions the study is for
- Diarrhea, Pneumonia, Acute Respiratory Tract Infection
- What is being tested?
- Zinc and vitamin A single dose at enrollment
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,482 participants
- Where
- 1 siteIndia
- Study dates
- Feb 1998to Sep 2000
- Phase
- Interventional
- 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 30 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Children in the age group 6-30 months
- Either sex
Who cannot join
- Refused consent
- Likely to move out of study area within the next four months
- Urgent admission to hospital on the enrollment day
- Had received massive dose of vitamin A within the two months before enrollment
Trial locations and contacts
1 site in 1 country.
India1 site
All India Institute of Medical Sciences
New Delhi, National Capital Territory of Delhi, 110029
About this study
Zinc deficiency is common in developing country children, as food intakes are often low, foods from animal sources are infrequently used, the bioavailability of zinc from staple cereal-based diets is limited and zinc losses occur during recurring diarrheal illnesses. Zinc deficiency is associated with impairment in immunological and other defenses against infection and increased rates of serious infections. Due to limitations in currently used biochemical markers, supplementation trials in populations likely to be deficient provide a reliable means of assessing health consequences of zinc deficiency.
A significantly lower incidence and prevalence of diarrhea has been observed in zinc supplemented developing country children in several placebo-controlled trials. The effect of routine zinc supplementation on lower respiratory tract infection is still unclear. We, therefore, evaluated the impact of daily zinc supplementation in a representative sample of children aged 6 to 30 months enrolled from a New Delhi slum area, with a sample size sufficient to determine the impact on the incidence of severe diarrhea and acute lower respiratory infection.
Read the detailed description
Diarrheal disease is a major cause of child mortality in developing countries. Currently, the management of diarrhea focuses on oral rehydration therapy in acute diarrhea. However, acute diarrhea accounts for only 1/3 of the diarrhea-related deaths, the majority of the remaining being caused by persistent diarrhea. Currently persistent diarrhea treatment is complex, not yet adapted to community settings and, hence, has only a marginal impact on diarrheal mortality. A major challenge is to develop and implement cost-effective community-based interventions that can be applied to children with diarrhea to prevent persistence.
The trial was implemented in the urban slum of Dakshinpuri comprising 15,000 dwellings and a population of about 75,000. Recent data from a neighboring community indicated that childhood malnutrition, zinc deficiency, diarrhea and lower respiratory tract infection were common. Children aged 6 to 30 months were identified through a door-to-door survey. Enrollment required that the parents give informed consent and that families did not intend to emigrate. Eligible children were individually randomized by a simple randomization scheme in blocks of 8 generated by a person at Statens Serum Institut, Denmark. The zinc and placebo syrups were prepared and packaged in unbreakable bottles by GK Pharma Aps (Koge, Denmark( and labeled with unique child number according to the randomization scheme. The zinc and placebo syrups were similar in appearance, taste and packaging.
The enrolled children were randomized to receive zinc gluconate (10 mg elemental zinc/day to infants and 20 mg/day to older children) or placebo daily for a period of 4 months. All included subjects were given a massive dose of vitamin A at enrollment in addition to zinc or placebo. A field attendant administered the syrup daily at home for 4 months except on Sundays, when the mother was asked to administer it. One bottle containing 250 mL was kept in the child's home and replaced monthly.
Field workers visited households every seventh day during the 4-month follow-up period. At each visit, information was obtained for the previous 7 days on history of fever, number and consistency of stools. If the child had diarrhea or vomiting, dehydration was assessed. Information was also obtained on cough, lower chest indrawing and on their illness characteristics and whether treatment was sought in the previous 7 days. Intervention impact was assessed on physician-diagnosed acute lower respiratory tract infections and pneumonia.
Blood was collected at baseline in all children to measure micronutrient status. Cognitive development was measured at baseline and end study using Bayelys Scales of Infant Development version II.
- Conditions
- Diarrhea, Pneumonia, Acute Respiratory Tract Infection
- Being tested
- Zinc and vitamin A single dose at enrollment, Placebo and vitamin A single dose at enrollment
- Keywords
- zinc, diarrhea, severe diarrhea, recurrent diarrhea, acute lower respiratory infection, pneumonia
- Medical subject headings
- Diarrhea, Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zinc and vitamin A single dose at enrollmentDrug
10 mg/day of elemental zinc as zinc gluconate to infants and 20 mg/day to older children
Placebo and vitamin A single dose at enrollmentDrug
Placebo was plain glucose. Vitamin A 100,000 IU to infants and 200,000 IU to older children
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | 10 mg/day of elemental zinc as zinc gluconate to infants and 20 mg/day to older children and Vitamin A 100,000 IU to infants and 200,000 IU to older children Receives: Drug: Zinc and vitamin A single dose at enrollment |
| 2 | Placebo comparator | Not described Receives: Drug: Placebo and vitamin A single dose at enrollment |
What is being measured
The primary outcome is the main question the study is designed to answer.
- To measure the impact of zinc and vitamin A on the duration of diarrheal illness
Measured: Weekly home visits for 6 months
Secondary outcomes (7)
- To measure the impact of supplementation on the outcome of acute diarrhea, particularly on the risk of persistence
Measured: Weekly home visits for 6 months
- To measure the impact of supplementation on immune response to parenteral live measles vaccine and oral live tetravalent rotavirus vaccine
Measured: At baseline and end study
To measure the impact of zinc and vitamin A on cognitive development
Measure the efficacy of daily zinc administration on cognitive development in children 12 to 18 months of age.
Measured: 6 months
-To measure the prevalence of zinc, copper, folate, vitamin B12, vitamin D, vitamin A and vitamin E deficiencies in the included children
From the plasma specimen collected at baseline, measure the concentration of various nutrients to estimate the prevalences of deficiency of these.
Measured: 6 months
-To measure the association between nutrient status at baseline (including micronutrient status) and subsequent diarrheal and respiratory illnesses
Measure to what extent plasma levels of zinc, copper, folate, vitamin B12, vitamin D, vitamin A, and vitamin E predicts infections over the subsequent 4 months.
Measured: 6 months
-To measure the association between nutrient status at baseline (including micronutrient status) and cognitive development.
We will measure to what extent, deficiencies of micronutrients predicts cognitive development in children 12 to 18 months of age.
Measured: 6 months
-To measure whether or not deficiencies of selected micronutrients modifies the effect of zinc on diarrhea or pneumonia
From the analyses of vitamins and minerals in plasma, we will measure to what extent deficiencies of these modifies the effect of zinc on pneumonia and diarrhea.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2006 (estimated)
- Study startFeb 1998
- Primary completionFeb 2000
- Study completionSep 2000
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for DiarrheaStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2,482 participants (actual)
Sponsor and investigators
- Lead sponsor
- Society for Applied Studies
- Sponsor type
- University, hospital or other
- Collaborators
- European Commission, World Health Organization, Norwegian Council of Universities' Committee for Development Research and Education
- Responsible party
- Principal investigator, NBhandari, Society for Applied Studies
- Investigators
- Maharaj K Bhan, MD, Principal investigator, All India Institute of Medical SciencesNita Bhandari, PhD, Principal investigator, Society for Applied Studies, New Delhi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00272116
- Sponsor's protocol ID
- ERB3514PL950371
- Other IDs
- IC18-CT96-0045
- Status last verified
- Apr 2012
- First submitted
- 2 Jan 2006
- Last updated
- 3 Apr 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Bhandari N, Bahl R, Taneja S, Strand T, Molbak K, Ulvik RJ, Sommerfelt H, Bhan MK. Effect of routine zinc supplementation on pneumonia in children aged 6 months to 3 years: randomised controlled trial in an urban slum. BMJ. 2002 Jun 8;324(7350):1358. doi: 10.1136/bmj.324.7350.1358.
PubMed 12052800Bhandari N, Bahl R, Taneja S, Strand T, Molbak K, Ulvik RJ, Sommerfelt H, Bhan MK. Substantial reduction in severe diarrheal morbidity by daily zinc supplementation in young north Indian children. Pediatrics. 2002 Jun;109(6):e86. doi: 10.1542/peds.109.6.e86.
PubMed 12042580Strand TA, Taneja S, Ueland PM, Refsum H, Bahl R, Schneede J, Sommerfelt H, Bhandari N. Cobalamin and folate status predicts mental development scores in North Indian children 12-18 mo of age. Am J Clin Nutr. 2013 Feb;97(2):310-7. doi: 10.3945/ajcn.111.032268. Epub 2013 Jan 2.
PubMed 23283502Manger MS, Taneja S, Strand TA, Ueland PM, Refsum H, Schneede J, Nygard O, Sommerfelt H, Bhandari N. Poor folate status predicts persistent diarrhea in 6- to 30-month-old north Indian children. J Nutr. 2011 Dec;141(12):2226-32. doi: 10.3945/jn.111.144220. Epub 2011 Oct 19.
PubMed 22013199Manger MS, Strand TA, Taneja S, Refsum H, Ueland PM, Nygard O, Schneede J, Sommerfelt H, Bhandari N. Cobalamin status modifies the effect of zinc supplementation on the incidence of prolonged diarrhea in 6- to 30-month-old north Indian children. J Nutr. 2011 Jun;141(6):1108-13. doi: 10.3945/jn.110.127415. Epub 2011 Apr 27.
PubMed 21525251Taneja S, Strand TA, Sommerfelt H, Bahl R, Bhandari N. Zinc supplementation for four months does not affect growth in young north Indian children. J Nutr. 2010 Mar;140(3):630-4. doi: 10.3945/jn.109.115766. Epub 2010 Jan 27.
PubMed 20107146
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Zinc and Vitamin A Supplementation on Diarrhea, Physical Growth and Immune Response in Malnourished Children
- ClinicalTrials.gov ID
- NCT00272116
- Acronym / sponsor ID
- ERB3514PL950371
- Conditions
- Diarrhea, Pneumonia, Acute Respiratory Tract Infection
- Keywords
- zinc, diarrhea, severe diarrhea, recurrent diarrhea, acute lower respiratory infection, pneumonia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,482 participants (actual)
- Lead sponsor
- Society for Applied StudiesUniversity, hospital or other
- Collaborators
- European Commission, World Health Organization, Norwegian Council of Universities' Committee for Development Research and Education
- Study start
- Feb 1998
- Primary completion
- Feb 2000 (actual)
- Study completion
- Sep 2000 (actual)
- First posted
- 4 Jan 2006 (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.
Zinc deficiency is common in developing country children, as food intakes are often low, foods from animal sources are infrequently used, the bioavailability of zinc from staple cereal-based diets is limited and zinc losses occur during recurring diarrheal illnesses. Zinc deficiency is associated with impairment in immunological and other defenses against infection and increased rates of serious infections. Due to limitations in currently used biochemical markers, supplementation trials in populations likely to be deficient provide a reliable means of assessing health consequences of zinc deficiency.
A significantly lower incidence and prevalence of diarrhea has been observed in zinc supplemented developing country children in several placebo-controlled trials. The effect of routine zinc supplementation on lower respiratory tract infection is still unclear. We, therefore, evaluated the impact of daily zinc supplementation in a representative sample of children aged 6 to 30 months enrolled from a New Delhi slum area, with a sample size sufficient to determine the impact on the incidence of severe diarrhea and acute lower respiratory infection.
Detailed description
Diarrheal disease is a major cause of child mortality in developing countries. Currently, the management of diarrhea focuses on oral rehydration therapy in acute diarrhea. However, acute diarrhea accounts for only 1/3 of the diarrhea-related deaths, the majority of the remaining being caused by persistent diarrhea. Currently persistent diarrhea treatment is complex, not yet adapted to community settings and, hence, has only a marginal impact on diarrheal mortality. A major challenge is to develop and implement cost-effective community-based interventions that can be applied to children with diarrhea to prevent persistence.
The trial was implemented in the urban slum of Dakshinpuri comprising 15,000 dwellings and a population of about 75,000. Recent data from a neighboring community indicated that childhood malnutrition, zinc deficiency, diarrhea and lower respiratory tract infection were common. Children aged 6 to 30 months were identified through a door-to-door survey. Enrollment required that the parents give informed consent and that families did not intend to emigrate. Eligible children were individually randomized by a simple randomization scheme in blocks of 8 generated by a person at Statens Serum Institut, Denmark. The zinc and placebo syrups were prepared and packaged in unbreakable bottles by GK Pharma Aps (Koge, Denmark( and labeled with unique child number according to the randomization scheme. The zinc and placebo syrups were similar in appearance, taste and packaging.
The enrolled children were randomized to receive zinc gluconate (10 mg elemental zinc/day to infants and 20 mg/day to older children) or placebo daily for a period of 4 months. All included subjects were given a massive dose of vitamin A at enrollment in addition to zinc or placebo. A field attendant administered the syrup daily at home for 4 months except on Sundays, when the mother was asked to administer it. One bottle containing 250 mL was kept in the child's home and replaced monthly.
Field workers visited households every seventh day during the 4-month follow-up period. At each visit, information was obtained for the previous 7 days on history of fever, number and consistency of stools. If the child had diarrhea or vomiting, dehydration was assessed. Information was also obtained on cough, lower chest indrawing and on their illness characteristics and whether treatment was sought in the previous 7 days. Intervention impact was assessed on physician-diagnosed acute lower respiratory tract infections and pneumonia.
Blood was collected at baseline in all children to measure micronutrient status. Cognitive development was measured at baseline and end study using Bayelys Scales of Infant Development version II.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Zinc and vitamin A single dose at enrollment10 mg/day of elemental zinc as zinc gluconate to infants and 20 mg/day to older children and Vitamin A 100,000 IU to infants and 200,000 IU to older children |
| 2 | Placebo comparator | Drug: Placebo and vitamin A single dose at enrollment |
Who may qualify
- Ages
- 6 to 30 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Children in the age group 6-30 months
- Either sex
Key exclusion criteria (4 listed)
- Refused consent
- Likely to move out of study area within the next four months
- Urgent admission to hospital on the enrollment day
- Had received massive dose of vitamin A within the two months before enrollment
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 |
|---|---|---|
| Zinc and vitamin A single dose at enrollment10 mg/day of elemental zinc as zinc gluconate to infants and 20 mg/day to older children | Drug | 1 |
| Placebo and vitamin A single dose at enrollmentPlacebo was plain glucose. Vitamin A 100,000 IU to infants and 200,000 IU to older children | Drug | 2 |
Primary outcome
- To measure the impact of zinc and vitamin A on the duration of diarrheal illness
Time frame: Weekly home visits for 6 months
7 secondary outcomes
- To measure the impact of supplementation on the outcome of acute diarrhea, particularly on the risk of persistence
Time frame: Weekly home visits for 6 months
- To measure the impact of supplementation on immune response to parenteral live measles vaccine and oral live tetravalent rotavirus vaccine
Time frame: At baseline and end study
To measure the impact of zinc and vitamin A on cognitive development
Time frame: 6 months
-To measure the prevalence of zinc, copper, folate, vitamin B12, vitamin D, vitamin A and vitamin E deficiencies in the included children
Time frame: 6 months
-To measure the association between nutrient status at baseline (including micronutrient status) and subsequent diarrheal and respiratory illnesses
Time frame: 6 months
-To measure the association between nutrient status at baseline (including micronutrient status) and cognitive development.
Time frame: 6 months
-To measure whether or not deficiencies of selected micronutrients modifies the effect of zinc on diarrhea or pneumonia
Time frame: 6 months
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 3 Apr 2012.
- Results publication: PubMed 12052800Bhandari N, Bahl R, Taneja S, Strand T, Molbak K, Ulvik RJ, Sommerfelt H, Bhan MK. Effect of routine zinc supplementation on pneumonia in children aged 6 months to 3 years: randomised controlled trial in an urban slum. BMJ. 2002 Jun 8;324(7350):1358. doi: 10.1136/bmj.324.7350.1358.
- Results publication: PubMed 12042580Bhandari N, Bahl R, Taneja S, Strand T, Molbak K, Ulvik RJ, Sommerfelt H, Bhan MK. Substantial reduction in severe diarrheal morbidity by daily zinc supplementation in young north Indian children. Pediatrics. 2002 Jun;109(6):e86. doi: 10.1542/peds.109.6.e86.
- Derived from this study: PubMed 23283502Strand TA, Taneja S, Ueland PM, Refsum H, Bahl R, Schneede J, Sommerfelt H, Bhandari N. Cobalamin and folate status predicts mental development scores in North Indian children 12-18 mo of age. Am J Clin Nutr. 2013 Feb;97(2):310-7. doi: 10.3945/ajcn.111.032268. Epub 2013 Jan 2.
- Derived from this study: PubMed 22013199Manger MS, Taneja S, Strand TA, Ueland PM, Refsum H, Schneede J, Nygard O, Sommerfelt H, Bhandari N. Poor folate status predicts persistent diarrhea in 6- to 30-month-old north Indian children. J Nutr. 2011 Dec;141(12):2226-32. doi: 10.3945/jn.111.144220. Epub 2011 Oct 19.
- Derived from this study: PubMed 21525251Manger MS, Strand TA, Taneja S, Refsum H, Ueland PM, Nygard O, Schneede J, Sommerfelt H, Bhandari N. Cobalamin status modifies the effect of zinc supplementation on the incidence of prolonged diarrhea in 6- to 30-month-old north Indian children. J Nutr. 2011 Jun;141(6):1108-13. doi: 10.3945/jn.110.127415. Epub 2011 Apr 27.
- Derived from this study: PubMed 20107146Taneja S, Strand TA, Sommerfelt H, Bahl R, Bhandari N. Zinc supplementation for four months does not affect growth in young north Indian children. J Nutr. 2010 Mar;140(3):630-4. doi: 10.3945/jn.109.115766. Epub 2010 Jan 27.
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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.
Maharaj K Bhan, MD principal investigator
All India Institute of Medical Sciences
Nita Bhandari, PhD principal investigator
Society for Applied Studies, New Delhi
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Zinc and vitamin A single dose at enrollment in people with Diarrhea and Pneumonia, run by Society for Applied Studies at 1 site in India.
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 2 inclusion and 4 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 3 Apr 2012. 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 India. 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.
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?
- To measure the impact of zinc and vitamin A on the duration of diarrheal illness (time frame: Weekly home visits for 6 months). 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 NCT00272116, which also lists 6 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 3 Apr 2012.