Clinical trial NCT02421653: RCT of Iodine-containing MNPs vs Oral Iodized Oil to Prevent Iodine Deficiency in Weaning Infants
Official title: A Randomised Controlled Trial of Iodine-containing Micronutrient Powders Versus Oral Iodised Oil to Prevent Iodine Deficiency in Weaning Infants
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Iodine Deficiency Disorders
Keywords: Micronutrient powders
MNP
Weaning
Home fortification
Iodine
Iodine deficiency
Iodine Deficiency Disorder
IDD
Infant
Growth
Iodised oil
Lead sponsor: Swiss Federal Institute of Technology
Sponsor class: OTHER
Collaborators: name: UNICEF
name: Global Alliance for Improved Nutrition
First posted: 2015-04-21
Enrollment: 0
Sex: ALL
Minimum age (years): 6
Maximum age (years): 9
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: In this study, two intervention strategies to address iodine deficiency and prevent iodine deficiency disorders in breast-fed weaning infants will be evaluated in a mild to moderate iodine-deficient population in Zamboanga del Norte, Philippines, Southeast Asia.

Detailed description: Universal salt iodization (USI) is the most effective means to ensure optimal population iodine status and prevent iodine deficiency. In countries where USI is well implemented it is generally assumed that iodine requirements of infants are covered through breast milk. As infants wean from breast milk, at the age of 4-6 months, iodized salt programs likely contribute little to their iodine intakes. Home-prepared complementary foods have low native iodine content and pediatric guidelines recommend no extra salt be given to infants during the first year making the dietary sources of iodine limited. Weaning infants may therefore be particularly vulnerable to iodine deficiency and its effects.

Iodine is an essential micronutrient and an integral component of the thyroid hormones, needed for normal growth and development, particularly of the brain. Thyroid hormones play a critical role for development of the central nervous system from early fetal life until well after birth. Thyroid hormone insufficiency during postnatal development is associated with sensorimotor and language deficits and hypothyroidism in infancy is associated with poorer language, memory skills, fine motor, auditory processing, attention and executive processing.

In iodine deficient areas where iodized salt coverage is poor, WHO, UNICEF and the International Council for the Control of Iodine Deficiency Disorders (ICCIDD) recommend infants between 7 and 24 months be given a daily dose of 90 µg iodine (potassium iodate) or an annual dose of 200 mg iodine (iodised oil). The scientific evidence for this recommendation is weak, however, and it is uncertain under what conditions the two prevention strategies may be applied and which of the two is best when.

The objective of this study is to evaluate the efficacy and safety of the two recommended intervention strategies in iodine-deficient weaning infants. The need for high-quality controlled studies to better understand the potential contribution and synergy of alternative strategies to help achieve optimal iodine nutrition in different population groups and settings has recently been defined as a major research priority.

Following a cross-sectional, pilot study, we will conduct a randomized controlled trial to assess the efficacy of two daily doses of iodine as potassium iodate (90 µg, 100% of the WHO recommended dose, and 45 µg, 50% of the WHO recommended dose) and the annual dose of 200 mg iodine in iodised oil, via a randomized, controlled trial in weaning infants of lactating mothers living in an area affected by mild to moderate iodine deficiency in Zamboanga del Norte, Philippines, Southeast Asia.

We will compare the efficacy of each of the iodine doses against each other, and against micro-nutrients given alone, estimate the optimal level of iodine for inclusion in MNPs, and report on the safety of these interventions in weaning infants.

This study will provide important guidance to public health experts, governments and international organisations to ensure normal infant thyroid function and growth and development.

Eligibility criteria: Except for the infant age criteria, the selection and exclusion criteria are the same for all participants (pilot and intervention):

Inclusion criteria:

* Ages:
* For pilot - aged 6 - 18 months (+2 weeks, no infant \< 6 months)
* For intervention - aged 6 - 9 months (+2 weeks, no infant \< 6 months)
* Born to a healthy singleton pregnancy
* Term (week 38 to 42) delivery
* Family residence at the study site for at least 12 months prior to the start of the study and anticipated residence for at least a further 12 months (mother and infant)
* Exclusively breastfed for at least 2 months, or if not, having received no other sources of iodine intake (in formula, supplements, or foods)
* Signed informed consent

Exclusion criteria:

* Suffering from severe acute malnutrition(\< 3 weight-for-height z-scores)
* Known history of medical illnesses
* Taking chronic medications (mother and infant)
* Use of iodine containing dietary supplements during the last 6 months (mother and infant)
* Exposure to iodine containing X-ray / CT contrast agent, skin disinfectants or medications during the last 6 months (mother and infant)
* Participation in any other clinical study (mother and infant) or participated in the pilot study (infant)

NB: Severe Acute Malnutrition is defined as being below 3 standard deviations (SD) of the WHO standard for weight-for-height ratio for infants and children aged 6 to 60 months. All infants identified with SAM will be excluded from the study and referred to hospital or nutrition clinic for treatment.

Primary outcomes:
measure: Infant urinary iodine concentration (UIC)
timeFrame: 24 weeks
measure: Infant dried blood spot thyroglobulin (DBS-Tg)
timeFrame: 24 weeks
Secondary outcomes:
measure: Infant dried blood spot TSH (DBS-TSH)
timeFrame: 24 weeks
measure: Infant dried blood spot total T4 (DBS-T4)
timeFrame: 24 weeks
measure: Infant somatic growth (head circumference, weight, length)
timeFrame: 24 weeks, and if results significant at this point, 52 weeks
measure: Thyroid autoimmunity
timeFrame: 24 weeks
measure: Safety (Composite measure of infant morbidities and infant mortality)
timeFrame: 24 weeks
Other outcomes:
measure: Infant urinary creatinine concentration
timeFrame: 24 weeks
measure: Infant urinary sodium concentration
timeFrame: 24 weeks
measure: Mother urinary iodine concentration (UIC)
timeFrame: 24 weeks
measure: Mother breast milk iodine concentration (BMIC)
timeFrame: 24 weeks
Locations:
Study officials:
affiliation: ETH Zuerich
name: Michael B Zimmermann, MD
role: PRINCIPAL_INVESTIGATOR
References: