DiarrheaNCT02428647
Lao Zinc Study: Effects of Two Forms of Daily Preventive Zinc Versus Therapeutic Zinc Supplementation
A study testing MNP, preventive zinc supplement and therapeutic zinc supplement in people with Diarrhea, run by University of California, Davis at 1 site in Laos.
Trial summary
The study will be conducted as a community-based, randomized, placebo-controlled, trial with four study groups. The overall objective of the study is to determine the optimal method for delivering zinc to young children, both for the prevention of zinc deficiency and treatment of diarrhea. Read more about this study
- Who is it for?
- Ages 6 to 23 monthsHealthy volunteers can take part
- Conditions the study is for
- Diarrhea
- What is being tested?
- MNP, preventive zinc supplement and therapeutic zinc supplement
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3,433 participants
- Where
- 1 siteLaos
- Study dates
- Sep 2015to Jul 2017
- 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 23 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Signed informed consent from at least one parent or primary caregiver
- Age 6-23 months initially
- Permanent resident of study area
- Planned availability during the period of the study
- Acceptance of home visitors
Who cannot join
- Weight-for-height z-score (WHZ) <-3Z with respect to WHO 2006 standards
- Presence of bipedal edema
- Severe illness warranting hospital referral
- Congenital abnormalities potentially interfering with growth
- Chronic medical condition (e.g. malignancy) requiring frequent medical attention
- Known HIV infection of index child or child's mother
Show all 9Show fewer
- Hemoglobin <70 g/L
- Currently consuming zinc supplements
- Current participation in any other clinical trial
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Lao Zinc Study: The Effects of Two Forms of Daily Preventive Zinc Supplementation Versus Therapeutic Zinc Supplementation for Diarrhea on Young Children's Physical Growth and Risk of New Episodes of Diarrhea
The study will be conducted as a community-based, randomized, placebo-controlled, trial with four study groups. The overall objective of the study is to determine the optimal method for delivering zinc to young children, both for the prevention of zinc deficiency and treatment of diarrhea. In particular, the investigators plan to compare the impact on physical growth, morbidity, micronutrient status, immune function, environmental enteric dysfunction, parasite burden and hair cortisol concentration of: 1) daily preventive zinc supplementation as a micronutrient powder (MNP); 2) placebo powders; 3) daily preventive zinc supplementation as dispersible tablets; 4) therapeutic zinc supplementation as dispersible tablets given in relation to episodes of diarrhea.
In addition to the major outcomes mentioned above, the investigators will monitor adherence to the interventions, neuro-behavioral development, and the occurrence of any adverse events.
Read the detailed description
Zinc is an essential nutrient that is required for children's normal growth and resistance to infections, including diarrhea and pneumonia, two major causes of child mortality. Current strategies for controlling the growth and infection-related complications of zinc deficiency include: 1) daily or weekly preventive zinc supplementation, and 2) therapeutic zinc supplementation for 10-14 days in relation to episodes of diarrhea. Information is needed on the relative impact of these intervention strategies on children's growth and risk of new episodes of diarrhea (and other infections).
Preventive zinc supplements can be delivered either as a single nutrient (zinc) supplement or as a multiple micronutrient (MMN) supplement, such as micronutrient powders (MNP) added to young children's complementary food. Available research indicates that zinc delivered in MNP at the currently recommended dose (4.1-5 mg/d) has not had a measurable impact on zinc-related functional outcomes, like growth and prevention of infection. Moreover, some studies of MMN supplements have detected a greater incidence of diarrhea in the MMN group than in the non-intervention or placebo control groups. Thus, despite the beneficial effects of MNP on prevention of anemia and enhancing iron status, questions have been raised about the desirability of providing zinc in MNP (containing iron and other nutrients) versus a single nutrient formulation offered between meals. For these reasons, the present study is designed to compare both the zinc delivery plan (i.e., preventive versus therapeutic supplementation) as well as the form of delivering zinc (i.e., as a dispersible tablet given between meals or as a MNP given with meals) and to permit assessment of any adverse effects of MNP on the incidence of diarrhea.
The study will be conducted as a community-based, randomized, placebo-controlled trial with four study groups in rural communities of Khammouane Province in Central Lao PDR.
The project team will enroll a total of ~3,400 children whose ages will range from 6-23 months. Children will be randomly assigned to one of four study group: 1) preventive zinc supplementation provided as LI-MNP plus ORS and placebo tablets for treatment of diarrhea; 2) placebo preventive supplementation provided as placebo powder plus ORS and placebo tablets for diarrhea ; 3) preventive zinc supplementation provided as dispersible zinc tablets (containing 7 mg zinc, to be given between meals) plus ORS and placebo tablets for diarrhea; and 4) therapeutic zinc supplementation provided as dispersible tablets (containing 20 mg zinc) for diarrhea plus ORS and placebo preventive tablets.
The major outcomes that will be monitored include adherence to the interventions; physical growth; incidence, duration and severity of episodes of diarrhea; changes in MN status; immune function; environmental enteric dysfunction; parasite burden; hair cortisol concentration; neuro-behavioral development; and the occurrence of any adverse events.
- Conditions
- Diarrhea
- Being tested
- MNP, preventive zinc supplement, therapeutic zinc supplement, preventive placebo supplement, therapeutic placebo supplement
- Keywords
- growth, plasma zinc concentration
- Medical subject headings
- Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MNPDietary supplement
MNP containing containing 10 mg zinc and 14 other nutrients, including 6 mg iron, 0.56 mg copper, 17 μg selenium, 90 μg iodine, 400 μg RE vitamin A, 5 μg vitamin D, 5 mg vitamin E, 30 mg ascorbic acid, 0.5 mg vitamin B1, 0.5 mg vitamin B2, 6 mg niacin, 0.5 mg vitamin B6, 0.9 μg vitamin B12, and 150 μg folate
preventive zinc supplementDietary supplement
7 mg zinc daily as dispersible tablet
therapeutic zinc supplementDietary supplement
20 mg zinc per day for 10 days during diarrhea episodes, as dispersible tablet
preventive placebo supplementDietary supplement
dispersible daily placebo tablet
therapeutic placebo supplementDietary supplement
dispersible placebo tablet for 10 days during diarrhea episodes
placebo powderDietary supplement
placebo powder
| Study group | Role | What they receive |
|---|---|---|
| micronutrient powder (MNP) | Active comparator | preventive zinc supplements provided as MNP (containing 10 mg zinc and 14 other nutrients, including 6 mg iron, 0.56 mg copper, 17 μg selenium, 90 μg iodine, 400 μg RE vitamin A, 5 μg vitamin D, 5 mg vitamin E, 30 mg ascorbic acid, 0.5 mg vitamin B1, 0.5 mg vitamin B2, 6 mg niacin, 0.5 mg vitamin B6, 0.9 μg vitamin B12, and 150 μg folate,) plus ORS and therapeutic placebo supplements for diarrhea Receives: Dietary Supplement: MNP; Dietary Supplement: therapeutic placebo supplement |
| placebo powder | Placebo comparator | placebo powder plus ORS and therapeutic placebo supplements for diarrhea Receives: Dietary Supplement: therapeutic placebo supplement; Dietary Supplement: placebo powder |
| preventive zinc supplements | Active comparator | preventive zinc supplements provided as dispersible zinc tablets (containing 7 mg zinc, to be given between meals) plus ORS and therapeutic placebo supplements for diarrhea Receives: Dietary Supplement: preventive zinc supplement; Dietary Supplement: therapeutic placebo supplement |
| therapeutic zinc supplements | Active comparator | preventive placebo supplements provided as dispersible tablets plus ORS and dispersible therapeutic zinc tablets (containing 20 mg zinc) for diarrhea Receives: Dietary Supplement: therapeutic zinc supplement; Dietary Supplement: preventive placebo supplement |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in length and length-for-age Z-score
Measured: 36 weeks
Change in weight and weight-for-age Z-score
Measured: 36 weeks
Incidence of diarrhea
Measured: 36 weeks
Change in hemoglobin concentration
Measured: 32 weeks
Change in micronutrient status
plasma zinc, ferritin, transferrin receptor; and retinol binding protein (RBP) concentrations, measured in a subsample of 560 participants, and controlling for the presence of elevated acute phase protein
Measured: 32 weeks
Innate and adaptive immune defense
production of cytokines by cultures of peripheral blood white blood cells; and change in concentrations of naïve and memory CD4 and CD8 T-cells and regulatory (Treg) T-cells in a sub-set of 500 children
Measured: 32 weeks
Secondary outcomes (9)
Change in mid-upper circumference
Measured: 36 weeks
Achievement of gross motor developmental milestones
Gross motor developmental milestones as recommended by the World Health Organization include: sitting without support, crawling, standing with assistance, walking with assistance, standing alone, walking alone
Measured: after 4, 8, 12, 16, 20, 24, 32 and 36 weeks
Change in stool calprotectin concentration
Measured: 36 weeks
Change in stool neopterin concentration
Measured: 36 weeks
Change in hair cortisol concentration
Measured: 36 weeks
Intestinal protozoa parasite infection
Intestinal protozoan infections will be assessed by a modified formalin-ethyl acetate concentration technique
Measured: 36 weeks
Helminths parasite infection
Helminth parasite infections will be assessed using duplicate Kato-Katz thick smears
Measured: 36 weeks
Acute and chronic sleep pattern
Assessed by Brief Infant Child Sleep Questionnaire
Measured: after 4, 8, 12, 16, 20, 24, 32 and 36 weeks
B-vitamin status
erythrocyte thiamine diphosphate, plasma folate and B12 concentrations and erythrocyte glutathione reductase activation coefficient (EGRac) measured in a randomly selected sub-sample of 260 children (MNP and control group only)
Measured: 36 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2015 (estimated)
- Study startSep 2015
- Primary completionMay 2017
- Study completionJul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for DiarrheaStudies of the same condition, open and under way.
- More trials run by University of California, DavisThe sponsor's other registered studies.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 3,433 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Collaborators
- Lao Tropical and Public Health Institute, USDA, Western Human Nutrition Research Center, University of British Columbia, Khon Kaen University, Nutrition International, The Mathile Institute for the Advancement of Human Nutrition
- Responsible party
- Sponsor
- Investigators
- Sonja Y Hess, PhD, Principal investigator, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02428647
- Sponsor's protocol ID
- 626187
- Other IDs
- 10-1347-UCALIF-07
- Status last verified
- Jan 2022
- First submitted
- 9 Feb 2015
- Last updated
- 20 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The complete de-identified dataset will be made publicly available within 3 years after completion of data collection. Associated data dictionaries will be made available along with the datasets.
Publications
Wessells KR, Brown KH, Kounnavong S, Barffour MA, Hinnouho GM, Sayasone S, Stephensen CB, Ratsavong K, Larson CP, Arnold CD, Harding KB, Reinhart GA, Lertmemongkolchai G, Fucharoen S, Bernstein RM, Hess SY. Comparison of two forms of daily preventive zinc supplementation versus therapeutic zinc supplementation for diarrhea on young children's physical growth and risk of infection: study design and rationale for a randomized controlled trial. BMC Nutr. 2018 Nov 29;4:39. doi: 10.1186/s40795-018-0247-6. eCollection 2018.
PubMed 32153900Hess SY, Hinnouho GM, Barffour MA, Bounheuang B, Arnold CD, Bell D, Marts TH, Kounnavong S. First Field Test of an Innovative, Wider Tape to Measure Mid-Upper Arm Circumference in Young Laotian Children. Food Nutr Bull. 2018 Mar;39(1):28-38. doi: 10.1177/0379572117742502. Epub 2017 Dec 19.
PubMed 29258337Hinnouho GM, Barffour MA, Wessells KR, Brown KH, Kounnavong S, Chanhthavong B, Ratsavong K, Kewcharoenwong C, Hess SY. Comparison of haemoglobin assessments by HemoCue and two automated haematology analysers in young Laotian children. J Clin Pathol. 2018 Jun;71(6):532-538. doi: 10.1136/jclinpath-2017-204786. Epub 2017 Dec 2.
PubMed 29197856Kingchaiyaphum B, Sanchaisuriya K, Fucharoen G, Chaibunruang A, Hess SY, Hinnouho GM, Barffour MA, Wessells KR, Kounnavong S, Fucharoen S. Hemoglobins F, A2 , and E levels in Laotian children aged 6-23 months with Hb E disorders: Effect of age, sex, and thalassemia types. Int J Lab Hematol. 2020 Jun;42(3):277-283. doi: 10.1111/ijlh.13164. Epub 2020 Feb 12.
PubMed 32048804Wessells KR, Hinnouho GM, Barffour MA, Arnold CD, Kounnavong S, Kewcharoenwong C, Lertmemongkolchai G, Schuster GU, Stephensen CB, Hess SY. Impact of Daily Preventive Zinc or Therapeutic Zinc Supplementation for Diarrhea on Plasma Biomarkers of Environmental Enteric Dysfunction among Rural Laotian Children: A Randomized Controlled Trial. Am J Trop Med Hyg. 2020 Feb;102(2):415-426. doi: 10.4269/ajtmh.19-0584.
PubMed 31889508Hess SY, Wessells KR, Hinnouho GM, Barffour MA, Sanchaisuriya K, Arnold CD, Brown KH, Larson CP, Fucharoen S, Kounnavong S. Iron status and inherited haemoglobin disorders modify the effects of micronutrient powders on linear growth and morbidity among young Lao children in a double-blind randomised trial. Br J Nutr. 2019 Oct 28;122(8):895-909. doi: 10.1017/S0007114519001715.
PubMed 31303184Hinnouho GM, Bernstein RM, Barffour MA, Arnold CD, Wessells KR, Ratsavong K, Bounheuang B, Kounnavong S, Hess SY. Impact of Two Forms of Daily Preventive Zinc or Therapeutic Zinc Supplementation for Diarrhea on Hair Cortisol Concentrations Among Rural Laotian Children: A Randomized Controlled Trial. Nutrients. 2018 Dec 27;11(1):47. doi: 10.3390/nu11010047.
PubMed 30591656Barffour MA, Hinnouho GM, Kounnavong S, Wessells KR, Ratsavong K, Bounheuang B, Chanhthavong B, Sitthideth D, Sengnam K, Arnold CD, Brown KH, Hess SY. Effects of Daily Zinc, Daily Multiple Micronutrient Powder, or Therapeutic Zinc Supplementation for Diarrhea Prevention on Physical Growth, Anemia, and Micronutrient Status in Rural Laotian Children: A Randomized Controlled Trial. J Pediatr. 2019 Apr;207:80-89.e2. doi: 10.1016/j.jpeds.2018.11.022. Epub 2018 Dec 21.
PubMed 30580974Wessells KR, Brown KH, Arnold CD, Barffour MA, Hinnouho GM, Killilea DW, Kounnavong S, Hess SY. Plasma and Nail Zinc Concentrations, But Not Hair Zinc, Respond Positively to Two Different Forms of Preventive Zinc Supplementation in Young Laotian Children: a Randomized Controlled Trial. Biol Trace Elem Res. 2021 Feb;199(2):442-452. doi: 10.1007/s12011-020-02163-2. Epub 2020 Apr 30.
PubMed 32356207Hinnouho GM, Wessells KR, Barffour MA, Sayasone S, Arnold CD, Kounnavong S, Hess SY. Impact of Different Strategies for Delivering Supplemental Zinc on Selected Fecal Markers of Environmental Enteric Dysfunction among Young Laotian Children: A Randomized Controlled Trial. Am J Trop Med Hyg. 2020 Oct;103(4):1416-1426. doi: 10.4269/ajtmh.20-0106.
PubMed 32618258Barffour MA, Hinnouho GM, Wessells KR, Kounnavong S, Ratsavong K, Sitthideth D, Bounheuang B, Sengnam K, Chanhthavong B, Arnold CD, Brown KH, Larson CP, Hess SY. Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial. J Glob Health. 2020 Jun;10(1):010424. doi: 10.7189/jogh.10.010424.
PubMed 32612816Kewcharoenwong C, Schuster GU, Wessells KR, Hinnouho GM, Barffour MA, Kounnavong S, Brown KH, Hess SY, Samer W, Tussakhon I, Peerson JM, Lertmemongkolchai G, Stephensen CB. Daily Preventive Zinc Supplementation Decreases Lymphocyte and Eosinophil Concentrations in Rural Laotian Children from Communities with a High Prevalence of Zinc Deficiency: Results of a Randomized Controlled Trial. J Nutr. 2020 Aug 1;150(8):2204-2213. doi: 10.1093/jn/nxaa037.
PubMed 32119742Kewcharoenwong C, Sein MM, Nithichanon A, Khongmee A, Wessells KR, Hinnouho GM, Barffour MA, Kounnavong S, Hess SY, Stephensen CB, Lertmemongkolchai G. Daily preventive zinc supplementation increases the antibody response against pathogenic Escherichia coli in children with zinc insufficiency: a randomised controlled trial. Sci Rep. 2022 Sep 27;12(1):16084. doi: 10.1038/s41598-022-20445-8.
PubMed 36167891Hinnouho GM, Hampel D, Shahab-Ferdows S, Barffour MA, McAnena L, Arnold CD, Ryan Wessells K, Kounnavong S, Allen LH, McNulty H, Hess SY. Daily supplementation of a multiple micronutrient powder improves folate but not thiamine, riboflavin, or vitamin B12 status among young Laotian children: a randomized controlled trial. Eur J Nutr. 2022 Oct;61(7):3423-3435. doi: 10.1007/s00394-022-02890-3. Epub 2022 May 9.
PubMed 35534778
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lao Zinc Study: The Effects of Two Forms of Daily Preventive Zinc Supplementation Versus Therapeutic Zinc Supplementation for Diarrhea on Young Children's Physical Growth and Risk of New Episodes of Diarrhea
- ClinicalTrials.gov ID
- NCT02428647
- Acronym / sponsor ID
- 626187
- Conditions
- Diarrhea
- Keywords
- growth, plasma zinc concentration
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3,433 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Collaborators
- Lao Tropical and Public Health Institute, USDA, Western Human Nutrition Research Center, University of British Columbia, Khon Kaen University, Nutrition International, The Mathile Institute for the Advancement of Human Nutrition
- Study start
- Sep 2015
- Primary completion
- May 2017 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 29 Apr 2015 (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 study will be conducted as a community-based, randomized, placebo-controlled, trial with four study groups. The overall objective of the study is to determine the optimal method for delivering zinc to young children, both for the prevention of zinc deficiency and treatment of diarrhea. In particular, the investigators plan to compare the impact on physical growth, morbidity, micronutrient status, immune function, environmental enteric dysfunction, parasite burden and hair cortisol concentration of: 1) daily preventive zinc supplementation as a micronutrient powder (MNP); 2) placebo powders; 3) daily preventive zinc supplementation as dispersible tablets; 4) therapeutic zinc supplementation as dispersible tablets given in relation to episodes of diarrhea.
In addition to the major outcomes mentioned above, the investigators will monitor adherence to the interventions, neuro-behavioral development, and the occurrence of any adverse events.
Detailed description
Zinc is an essential nutrient that is required for children's normal growth and resistance to infections, including diarrhea and pneumonia, two major causes of child mortality. Current strategies for controlling the growth and infection-related complications of zinc deficiency include: 1) daily or weekly preventive zinc supplementation, and 2) therapeutic zinc supplementation for 10-14 days in relation to episodes of diarrhea. Information is needed on the relative impact of these intervention strategies on children's growth and risk of new episodes of diarrhea (and other infections).
Preventive zinc supplements can be delivered either as a single nutrient (zinc) supplement or as a multiple micronutrient (MMN) supplement, such as micronutrient powders (MNP) added to young children's complementary food. Available research indicates that zinc delivered in MNP at the currently recommended dose (4.1-5 mg/d) has not had a measurable impact on zinc-related functional outcomes, like growth and prevention of infection. Moreover, some studies of MMN supplements have detected a greater incidence of diarrhea in the MMN group than in the non-intervention or placebo control groups. Thus, despite the beneficial effects of MNP on prevention of anemia and enhancing iron status, questions have been raised about the desirability of providing zinc in MNP (containing iron and other nutrients) versus a single nutrient formulation offered between meals. For these reasons, the present study is designed to compare both the zinc delivery plan (i.e., preventive versus therapeutic supplementation) as well as the form of delivering zinc (i.e., as a dispersible tablet given between meals or as a MNP given with meals) and to permit assessment of any adverse effects of MNP on the incidence of diarrhea.
The study will be conducted as a community-based, randomized, placebo-controlled trial with four study groups in rural communities of Khammouane Province in Central Lao PDR.
The project team will enroll a total of ~3,400 children whose ages will range from 6-23 months. Children will be randomly assigned to one of four study group: 1) preventive zinc supplementation provided as LI-MNP plus ORS and placebo tablets for treatment of diarrhea; 2) placebo preventive supplementation provided as placebo powder plus ORS and placebo tablets for diarrhea ; 3) preventive zinc supplementation provided as dispersible zinc tablets (containing 7 mg zinc, to be given between meals) plus ORS and placebo tablets for diarrhea; and 4) therapeutic zinc supplementation provided as dispersible tablets (containing 20 mg zinc) for diarrhea plus ORS and placebo preventive tablets.
The major outcomes that will be monitored include adherence to the interventions; physical growth; incidence, duration and severity of episodes of diarrhea; changes in MN status; immune function; environmental enteric dysfunction; parasite burden; hair cortisol concentration; neuro-behavioral development; and the occurrence of any adverse events.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| micronutrient powder (MNP) | Active comparator | Dietary Supplement: MNP, Dietary Supplement: therapeutic placebo supplementpreventive zinc supplements provided as MNP (containing 10 mg zinc and 14 other nutrients, including 6 mg iron, 0.56 mg copper, 17 μg selenium, 90 μg iodine, 400 μg RE vitamin A, 5 μg vitamin D, 5 mg vitamin E, 30 mg ascorbic acid, 0.5 mg vitamin B1, 0.5 mg vitamin B2, 6 mg niacin, 0.5 mg vitamin B6, 0.9 μg vitamin B12, and 150 μg folate,) plus ORS and therapeutic placebo supplements for diarrhea |
| placebo powder | Placebo comparator | Dietary Supplement: therapeutic placebo supplement, Dietary Supplement: placebo powderplacebo powder plus ORS and therapeutic placebo supplements for diarrhea |
| preventive zinc supplements | Active comparator | Dietary Supplement: preventive zinc supplement, Dietary Supplement: therapeutic placebo supplementpreventive zinc supplements provided as dispersible zinc tablets (containing 7 mg zinc, to be given between meals) plus ORS and therapeutic placebo supplements for diarrhea |
| therapeutic zinc supplements | Active comparator | Dietary Supplement: therapeutic zinc supplement, Dietary Supplement: preventive placebo supplementpreventive placebo supplements provided as dispersible tablets plus ORS and dispersible therapeutic zinc tablets (containing 20 mg zinc) for diarrhea |
Who may qualify
- Ages
- 6 to 23 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Signed informed consent from at least one parent or primary caregiver
- Age 6-23 months initially
- Permanent resident of study area
- Planned availability during the period of the study
- Acceptance of home visitors
Key exclusion criteria (9 listed)
- Weight-for-height z-score (WHZ) <-3Z with respect to WHO 2006 standards
- Presence of bipedal edema
- Severe illness warranting hospital referral
- Congenital abnormalities potentially interfering with growth
- Chronic medical condition (e.g. malignancy) requiring frequent medical attention
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 |
|---|---|---|
| MNPMNP containing containing 10 mg zinc and 14 other nutrients, including 6 mg iron, 0.56 mg copper, 17 μg selenium, 90 μg iodine, 400 μg RE vitamin A, 5 μg vitamin D, 5 mg vitamin E, 30 mg ascorbic acid, 0.5 mg vitamin B1, 0.5 mg vitamin B2, 6 mg niacin, 0.5 mg vitamin B6, 0.9 μg vitamin B12, and 150 μg folate | Dietary supplement | micronutrient powder (MNP) |
| preventive zinc supplement7 mg zinc daily as dispersible tablet | Dietary supplement | preventive zinc supplements |
| therapeutic zinc supplement20 mg zinc per day for 10 days during diarrhea episodes, as dispersible tablet | Dietary supplement | therapeutic zinc supplements |
| preventive placebo supplementdispersible daily placebo tablet | Dietary supplement | therapeutic zinc supplements |
| therapeutic placebo supplementdispersible placebo tablet for 10 days during diarrhea episodes | Dietary supplement | micronutrient powder (MNP), placebo powder, preventive zinc supplements |
| placebo powderplacebo powder | Dietary supplement | placebo powder |
Primary outcome
Change in length and length-for-age Z-score
Time frame: 36 weeks
Change in weight and weight-for-age Z-score
Time frame: 36 weeks
Incidence of diarrhea
Time frame: 36 weeks
Change in hemoglobin concentration
Time frame: 32 weeks
Change in micronutrient status
Time frame: 32 weeks
plasma zinc, ferritin, transferrin receptor; and retinol binding protein (RBP) concentrations, measured in a subsample of 560 participants, and controlling for the presence of elevated acute phase protein
Innate and adaptive immune defense
Time frame: 32 weeks
production of cytokines by cultures of peripheral blood white blood cells; and change in concentrations of naïve and memory CD4 and CD8 T-cells and regulatory (Treg) T-cells in a sub-set of 500 children
9 secondary outcomes
Change in mid-upper circumference
Time frame: 36 weeks
Achievement of gross motor developmental milestones
Time frame: after 4, 8, 12, 16, 20, 24, 32 and 36 weeks
Change in stool calprotectin concentration
Time frame: 36 weeks
Change in stool neopterin concentration
Time frame: 36 weeks
Change in hair cortisol concentration
Time frame: 36 weeks
Intestinal protozoa parasite infection
Time frame: 36 weeks
Helminths parasite infection
Time frame: 36 weeks
Acute and chronic sleep pattern
Time frame: after 4, 8, 12, 16, 20, 24, 32 and 36 weeks
B-vitamin status
Time frame: 36 weeks
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 20 Jan 2022.
- Background: PubMed 32153900Wessells KR, Brown KH, Kounnavong S, Barffour MA, Hinnouho GM, Sayasone S, Stephensen CB, Ratsavong K, Larson CP, Arnold CD, Harding KB, Reinhart GA, Lertmemongkolchai G, Fucharoen S, Bernstein RM, Hess SY. Comparison of two forms of daily preventive zinc supplementation versus therapeutic zinc supplementation for diarrhea on young children's physical growth and risk of infection: study design and rationale for a randomized controlled trial. BMC Nutr. 2018 Nov 29;4:39. doi: 10.1186/s40795-018-0247-6. eCollection 2018.
- Results publication: PubMed 29258337Hess SY, Hinnouho GM, Barffour MA, Bounheuang B, Arnold CD, Bell D, Marts TH, Kounnavong S. First Field Test of an Innovative, Wider Tape to Measure Mid-Upper Arm Circumference in Young Laotian Children. Food Nutr Bull. 2018 Mar;39(1):28-38. doi: 10.1177/0379572117742502. Epub 2017 Dec 19.
- Results publication: PubMed 29197856Hinnouho GM, Barffour MA, Wessells KR, Brown KH, Kounnavong S, Chanhthavong B, Ratsavong K, Kewcharoenwong C, Hess SY. Comparison of haemoglobin assessments by HemoCue and two automated haematology analysers in young Laotian children. J Clin Pathol. 2018 Jun;71(6):532-538. doi: 10.1136/jclinpath-2017-204786. Epub 2017 Dec 2.
- Results publication: PubMed 32048804Kingchaiyaphum B, Sanchaisuriya K, Fucharoen G, Chaibunruang A, Hess SY, Hinnouho GM, Barffour MA, Wessells KR, Kounnavong S, Fucharoen S. Hemoglobins F, A2 , and E levels in Laotian children aged 6-23 months with Hb E disorders: Effect of age, sex, and thalassemia types. Int J Lab Hematol. 2020 Jun;42(3):277-283. doi: 10.1111/ijlh.13164. Epub 2020 Feb 12.
- Results publication: PubMed 31889508Wessells KR, Hinnouho GM, Barffour MA, Arnold CD, Kounnavong S, Kewcharoenwong C, Lertmemongkolchai G, Schuster GU, Stephensen CB, Hess SY. Impact of Daily Preventive Zinc or Therapeutic Zinc Supplementation for Diarrhea on Plasma Biomarkers of Environmental Enteric Dysfunction among Rural Laotian Children: A Randomized Controlled Trial. Am J Trop Med Hyg. 2020 Feb;102(2):415-426. doi: 10.4269/ajtmh.19-0584.
- Results publication: PubMed 31303184Hess SY, Wessells KR, Hinnouho GM, Barffour MA, Sanchaisuriya K, Arnold CD, Brown KH, Larson CP, Fucharoen S, Kounnavong S. Iron status and inherited haemoglobin disorders modify the effects of micronutrient powders on linear growth and morbidity among young Lao children in a double-blind randomised trial. Br J Nutr. 2019 Oct 28;122(8):895-909. doi: 10.1017/S0007114519001715.
- Results publication: PubMed 30591656Hinnouho GM, Bernstein RM, Barffour MA, Arnold CD, Wessells KR, Ratsavong K, Bounheuang B, Kounnavong S, Hess SY. Impact of Two Forms of Daily Preventive Zinc or Therapeutic Zinc Supplementation for Diarrhea on Hair Cortisol Concentrations Among Rural Laotian Children: A Randomized Controlled Trial. Nutrients. 2018 Dec 27;11(1):47. doi: 10.3390/nu11010047.
- Results publication: PubMed 30580974Barffour MA, Hinnouho GM, Kounnavong S, Wessells KR, Ratsavong K, Bounheuang B, Chanhthavong B, Sitthideth D, Sengnam K, Arnold CD, Brown KH, Hess SY. Effects of Daily Zinc, Daily Multiple Micronutrient Powder, or Therapeutic Zinc Supplementation for Diarrhea Prevention on Physical Growth, Anemia, and Micronutrient Status in Rural Laotian Children: A Randomized Controlled Trial. J Pediatr. 2019 Apr;207:80-89.e2. doi: 10.1016/j.jpeds.2018.11.022. Epub 2018 Dec 21.
- Results publication: PubMed 32356207Wessells KR, Brown KH, Arnold CD, Barffour MA, Hinnouho GM, Killilea DW, Kounnavong S, Hess SY. Plasma and Nail Zinc Concentrations, But Not Hair Zinc, Respond Positively to Two Different Forms of Preventive Zinc Supplementation in Young Laotian Children: a Randomized Controlled Trial. Biol Trace Elem Res. 2021 Feb;199(2):442-452. doi: 10.1007/s12011-020-02163-2. Epub 2020 Apr 30.
- Results publication: PubMed 32618258Hinnouho GM, Wessells KR, Barffour MA, Sayasone S, Arnold CD, Kounnavong S, Hess SY. Impact of Different Strategies for Delivering Supplemental Zinc on Selected Fecal Markers of Environmental Enteric Dysfunction among Young Laotian Children: A Randomized Controlled Trial. Am J Trop Med Hyg. 2020 Oct;103(4):1416-1426. doi: 10.4269/ajtmh.20-0106.
- Results publication: PubMed 32612816Barffour MA, Hinnouho GM, Wessells KR, Kounnavong S, Ratsavong K, Sitthideth D, Bounheuang B, Sengnam K, Chanhthavong B, Arnold CD, Brown KH, Larson CP, Hess SY. Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial. J Glob Health. 2020 Jun;10(1):010424. doi: 10.7189/jogh.10.010424.
- Results publication: PubMed 32119742Kewcharoenwong C, Schuster GU, Wessells KR, Hinnouho GM, Barffour MA, Kounnavong S, Brown KH, Hess SY, Samer W, Tussakhon I, Peerson JM, Lertmemongkolchai G, Stephensen CB. Daily Preventive Zinc Supplementation Decreases Lymphocyte and Eosinophil Concentrations in Rural Laotian Children from Communities with a High Prevalence of Zinc Deficiency: Results of a Randomized Controlled Trial. J Nutr. 2020 Aug 1;150(8):2204-2213. doi: 10.1093/jn/nxaa037.
- Individual participant dataSharing planned: Yes. The complete de-identified dataset will be made publicly available within 3 years after completion of data collection. Associated data dictionaries will be made available along with the datasets.
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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.
Sonja Y Hess, PhD principal investigator
University of California, Davis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing MNP, preventive zinc supplement and therapeutic zinc supplement in people with Diarrhea, run by University of California, Davis at 1 site in Laos.
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 5 inclusion and 9 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 20 Jan 2022. 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 Laos. 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?
Change in length and length-for-age Z-score (time frame: 36 weeks). The study lists 6 primary outcomes in all. 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 NCT02428647, which also lists 14 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 20 Jan 2022.