NCT02428647

Brief 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. 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
3,433

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Sep 2015

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 9, 2015

Completed
3 months until next milestone

First Posted

Study publicly available on registry

April 29, 2015

Completed
4 months until next milestone

Study Start

First participant enrolled

September 1, 2015

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2017

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2017

Completed
Last Updated

January 20, 2022

Status Verified

January 1, 2022

Enrollment Period

1.7 years

First QC Date

February 9, 2015

Last Update Submit

January 4, 2022

Conditions

Diarrhea

Keywords

growthplasma zinc concentration

Outcome Measures

Primary Outcomes (6)

  • Change in length and length-for-age Z-score

    36 weeks

  • Change in weight and weight-for-age Z-score

    36 weeks

  • Incidence of diarrhea

    36 weeks

  • Change in hemoglobin concentration

    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

    32 weeks

  • Innate and adaptive immune defense

    production of cytokines by cultures of peripheral blood white blood cells; and change in concentrations of naĂ¯ve and memory CD4 and CD8 T-cells and regulatory (Treg) T-cells in a sub-set of 500 children

    32 weeks

Secondary Outcomes (9)

  • Change in mid-upper circumference

    36 weeks

  • Achievement of gross motor developmental milestones

    after 4, 8, 12, 16, 20, 24, 32 and 36 weeks

  • Change in stool calprotectin concentration

    36 weeks

  • Change in stool neopterin concentration

    36 weeks

  • Change in hair cortisol concentration

    36 weeks

  • +4 more secondary outcomes

Other Outcomes (2)

  • Incidence of serious adverse events

    36 weeks

  • Incidence of any non-serious adverse events

    36 weeks

Study Arms (4)

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

Dietary Supplement: MNPDietary Supplement: therapeutic placebo supplement

placebo powder

PLACEBO COMPARATOR

placebo powder plus ORS and therapeutic placebo supplements for diarrhea

Dietary Supplement: therapeutic placebo supplementDietary 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

Dietary Supplement: preventive zinc supplementDietary 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

Dietary Supplement: therapeutic zinc supplementDietary Supplement: preventive placebo supplement

Interventions

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

micronutrient powder (MNP)
preventive zinc supplementDIETARY_SUPPLEMENT

7 mg zinc daily as dispersible tablet

preventive zinc supplements
therapeutic zinc supplementDIETARY_SUPPLEMENT

20 mg zinc per day for 10 days during diarrhea episodes, as dispersible tablet

therapeutic zinc supplements
preventive placebo supplementDIETARY_SUPPLEMENT

dispersible daily placebo tablet

therapeutic zinc supplements
therapeutic placebo supplementDIETARY_SUPPLEMENT

dispersible placebo tablet for 10 days during diarrhea episodes

micronutrient powder (MNP)placebo powderpreventive zinc supplements
placebo powderDIETARY_SUPPLEMENT

placebo powder

placebo powder

Eligibility Criteria

Age6 Months - 23 Months
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • Hemoglobin \<70 g/L
  • Currently consuming zinc supplements
  • Current participation in any other clinical trial

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Lao Tropical and Public Health Institute

Vientiane, Laos

Location

Related Publications (14)

  • 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.

    PMID: 32153900BACKGROUND

  • Hess 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.

    PMID: 29258337RESULT

  • Hinnouho 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.

    PMID: 29197856RESULT

  • Kingchaiyaphum 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.

    PMID: 32048804RESULT

  • Wessells 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.

    PMID: 31889508RESULT

  • Hess 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.

    PMID: 31303184RESULT

  • Hinnouho 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.

    PMID: 30591656RESULT

  • Barffour 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.

    PMID: 30580974RESULT

  • Wessells 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.

    PMID: 32356207RESULT

  • Hinnouho 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.

    PMID: 32618258RESULT

  • Barffour 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.

    PMID: 32612816RESULT

  • Kewcharoenwong 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.

    PMID: 32119742RESULT

  • Kewcharoenwong 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.

    PMID: 36167891DERIVED

  • Hinnouho 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.

    PMID: 35534778DERIVED

MeSH Terms

Conditions

Diarrhea

Condition Hierarchy (Ancestors)

Signs and Symptoms, DigestiveSigns and SymptomsPathological Conditions, Signs and Symptoms

Study Officials

  • Sonja Y Hess, PhD

    University of California, Davis

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 9, 2015

First Posted

April 29, 2015

Study Start

September 1, 2015

Primary Completion

May 1, 2017

Study Completion

July 1, 2017

Last Updated

January 20, 2022

Record last verified: 2022-01

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, SAP, ICF
Time Frame
Summer 2020
Access Criteria
Publicly available
More information

Locations

LA(1)