Clinical trial NCT02915536: Exploration of Effects of Excessive Iodine on Children and Tolerable Upper Intake Level of Iodine for Children
Official title: Exploration of Effects of Excessive Iodine on Children and Tolerable Upper Intake Level of Iodine for Children
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Iodine Disorders
Keywords: iodine excess
thyroid disease
children
tolerable upper intake level
Lead sponsor: Tianjin Medical University
Sponsor class: OTHER
Collaborators: name: The Shandong Institute for Endemic Disease Control and Research
First posted: 2016-09-27
Enrollment: 2229
Sex: ALL
Minimum age (years): 7
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: High water iodine areas in Shandong are far-ranging. An investigation in 2005 showed that water iodine content exceeded 150μg/L in 17 of the 20 counties, while water iodine in the other 3 exceeded 300μg/L. Regions with water iodine content in the range of 150-800µg/L were chosen as, with a corresponding UIE range of 300-800µg/L, were selected as high iodine intake (HI) areas for the study. Regions with water iodine content in the range of 10-100µg/L with a corresponding UIE range of 100-299µg/L were selected as adequate iodine intake (AI) study areas. Areas with high fluorine will be excluded. One to six primary schools were selected from each city by randomly sampling. Children were selected from these schools.

Brief summary: With the implementation of Universal Salt Iodization (USI) in 1995, China has successfully combated Iodine Deficiency Diseases (IDD). However, China is a country with a complicated iodine geographical environment with wide natural variation in the iodine content of drinking water. It has been reported that the water iodine of at least 11 provinces and cities in China is high, with nearly 31 million people exposed to the risks of excessive iodine intake. This has raised a new public health concern that a safe upper level of iodine intake should be established to ensure that people avoid ingesting excessive iodine intake while continuing to implement USI to control IDD. The investigators have successfully explored the tolerable upper intake level (UL) of iodine for Chinese adults by conducting a randomized double-blinded trial in 256 euthyroid volunteers. However, due to limited data on the safe upper intake level of iodine for children worldwide, current ULs of iodine for children are extrapolated from those for adults based on body weight or body surface area. As it is impossible to ethically conduct a randomized clinical trial regarding excessive iodine intake in children, the investigators plan an observational study to investigate children who have been living with different drinking water iodine levels for over 5 years, observing the changes of thyroid function in response to each iodine exposure level. Subtle changes in thyroid function and thyroid volume of children corresponding to different iodine intake levels will be determined, which will contribute to the establishment of UL of iodine for children.

The aim was:

1. To establish the tolerable upper intake level (UL) of iodine for children of China.
2. To define the adverse effects of excess iodine on children.
3. To monitor the iodine status of children living in high water iodine areas in China.

Detailed description: The project is designed as a cross-sectional comparative epidemiological study, to be conducted in areas with high water iodine and adequate iodine intake, respectively. The research will include the following three stages.

First stage: In an initial contact phase of the study, workshops on the subject matter will be held in Shandong province. Regions will be sampled according to the monitoring data on water iodine collected by the Shandong Institute for Endemic Disease Control and Research, which will be a collaborative department for this study, as well as the pre-investigation. Areas in Shandong with water iodine ranging from 150μg/L to 800μg/L iodine, corresponding to urinary iodine excretion (UIE) of 300-800μg/L, will be investigated as high iodine intake areas (HI); regions with varying water iodine levels within this range will be included. Matching areas in Shandong with 10-100μg/L iodine in water, corresponding to UIE of 100-299μg/L, will be selected as the comparison areas of adequate iodine intake (AI). Refresher courses will be given to investigators and the capacity of laboratory staff will be updated. All relevant local authorities will be properly contacted. Pre-investigations will be conducted to determine the water iodine level and the former iodine status of residents, which will help the investigators to select suitable study areas. A pilot study will be conducted in a small number of subjects, including 24h urine collection and 3d dietary record to ensure that these methods are appropriate and feasible.

Second stage: A cross-sectional study of iodine intake and thyroid function in 7-14-yr-old children will be carried out. This stage mainly includes two parts.

In Part 1, 24-h and spot urinary samples (2 times) from all children will be collected to precisely evaluate the daily iodine intake of subjects. Spot urinary samples will be taken before collection of the 24-h urine samples. Teachers and parents will be trained to help children in performing the collection. 3d dietary records will be used to collect information on food and nutrient intake of participants. The parents (or guardian) and children will be trained on how to record food intake. The dietary record may be started any day of a week and correspond to the day of urine collection. The record will comprise all home food and water intake as well as out-of-home food consumption. Food frequency questionnaires (FFQ) will be used in combination with the dietary records to evaluate long-term habitual iodine intake. Simultaneously, food samples, including locally-consumed foods with relatively high iodine content and those which local residents generally consume frequently, will be sampled to determine iodine content, as will salt and water.

In Part 2, Blood samples will be collected to evaluate thyroid function and thyroid auto-antibodies, and thyroid volume of children will be detected by ultrasonography which will be conducted by professional technicians

Third stage: Iodine intake of all children will be calculated precisely and comprehensively through both 24-h UIE and dietary iodine intake (as described in Part 1). Adverse effects will be defined by parameters detected in Part 2.

Eligibility criteria: Inclusion Criteria:

* Healthy
* Native born or residents of Shandong province for at least 5 years.

Exclusion Criteria:

* Previous history of thyroid diseases or medication intake (including iodine supplements)
* protein-energy malnutrition in the long term

Primary outcomes:
measure: thyroid goiter confirmed by ultrasonographic thyroid volume
timeFrame: 1 year
Secondary outcomes:
measure: thyroid dysfunction confirmed by serum concentrations of FT4, FT3, and TSH with an automated chemiluminescent immunoassay by using diagnostic kits from Bayer Health Care, Siemens
timeFrame: 1 year
Other outcomes:
measure: thyroid dysfunction confirmed by serum concentrations of TPOAb and TGAb with radioimmunoassay by using kits from the Beijing North Institution
timeFrame: 1 year
Locations:
Study officials:
affiliation: Tianjin Medical University
name: Wanqi Zhang, Doctor
role: STUDY_CHAIR
affiliation: The Shandong Institute for Endemic Disease Control and Research
name: Jianchao Bian
role: PRINCIPAL_INVESTIGATOR
affiliation: Tianjin Medical University
name: Zuoliang Dong, Master
role: PRINCIPAL_INVESTIGATOR
affiliation: Tianjin Medical University
name: Laixiang Lin, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Tianjin Medical University
name: Jun Shen, Master
role: PRINCIPAL_INVESTIGATOR
affiliation: The Shandong Institute for Endemic Disease Control and Research
name: Jinbiao Wang
role: PRINCIPAL_INVESTIGATOR
affiliation: The Shandong Institute for Endemic Disease Control and Research
name: Wen Jiang, Master
role: PRINCIPAL_INVESTIGATOR
affiliation: Tianjin Medical University
name: Zhongna Sang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Tianjin Medical University
name: Long Tan, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Tianjin Medical University
name: Wen Chen, Master
role: PRINCIPAL_INVESTIGATOR
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