Clinical trial NCT05141968: Vitamin D Supplementation and Glycemic Control Improvement Among Type 1 Diabetic Children
Official title: The Effects of Vitamin D Supplementation on Glycemic Control in Children With Type 1 Diabetes Mellitus in Gaza Strip, A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes Mellitus
Vitamin D Deficiency
Keywords: Vitamin D Supplementation
Glycemic Control
Type 1 Diabetes Mellitus
Gaza Strip
Randomized Controlled Trial.
Lead sponsor: Al-Azhar University
Sponsor class: OTHER
First posted: 2021-12-02
Enrollment: 80
Sex: ALL
Minimum age (years): 4
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: Type 1 diabetes mellitus (T1DM) is an immune-mediated disease characterized by diminished insulin secretion due to damage to islets of Langerhans in the pancreas, which eventually results in high levels of glucose in the blood. According to World Diabetes Foundation, in Palestine, 4.4% of diabetic patients are diagnosed with T1DM, while 95.3% are diagnosed with type 2 diabetes (T2DM) (World Diabetes Foundation, 2020).

Observational studies have reliably provided evidence that T1DM patients with acceptable glycemic control have higher 25(OH)D levels than T1DM with lesser glycemic control. Additionally, it has been specified by some of the research-based studies that there is a strong connection between the deficiency of vitamin D and the incidence of T1DM.

In interventional studies of T1DM children and adults, repletion of vitamin D in deficient individuals improved HbA1c in a period of 12 weeks. Participants were more likely to achieve HbA1c \< 7.8% if they had higher 25(OH)D levels on week 12 than on baseline, especially if 25(OH)D levels were exceeded 51 nmol/l.

According to the Food and Drug Administration (FDA), The Institute of Medicine's (IOM) recommended Upper Limit (UL) for chronic Vitamin D intake for infants (children less than 1 year of age) is 25 mcg/day (1,000 IU/d), and for children age 1 year and older the recommended UL is 50 mcg/day (2,000 IU/d) (Institute of Medicine Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, 1997).

Despite a large amount of evidence from observational and experimental studies supporting the effects of vitamin D on glucose metabolism and the immune system, results from clinical studies remain inconsistent, which makes it impossible to recommend vitamin D supplementation for the treatment of T1DM. Therefore, this study aimed to investigate the status of vitamin D among T1DM children for vitamin and to examine the effects of vitamin D supplementation on glycemic control in children with T1DM. This is the first randomized controlled trial that studied the effects of vitamin D supplementation on glycemic control among T1DM children in the Gaza Strip, Palestine.

Detailed description: 2.1 Study design The study design was experimental, A randomized controlled trial. 2.2 Study setting The study was conducted at the endocrinology outpatients' clinic at AL-RANTISI PEDIATRIC HOSPITAL in Gaza Strip.

2.3 Study Sample After getting the ethical approval, data were collected throughout 3 months, starting from October 2017 to January 2018. In this period, 80 children who were less than 14 years old were diagnosed with T1DM which was indicated through fasting blood glucose level greater than 126 mg/dl or HbA1c cut point of ≥6.5% (American Diabetes Association, 2010), and had vitamin D deficiency which indicated by its levels of less than 12 ng/ml (Sullivan, 2019), were recruited from endocrinology outpatients' clinic at AL-RANTISI PEDIATRIC HOSPITAL in Gaza Strip.

2.4 Sampling

A stratified random sampling technique was applied to assign children with the previously mentioned criteria into two groups. The first group is the interventional (experimental) group that received vitamin D supplements (2000 IU/day) and the second group is the control group that did not receive any supplements. Both groups were on their regular diet and treatment, but one group was put on vitamin D supplement and the other group received a placebo instead. According to previous studies and after the direct supervision from the treating pediatrician and endocrinologist, the best preparation and dosage of vitamin D was used (According to FDA the recommended dose for children age 1 year and older is 2,000 IU/day). The two groups were defined as follows:

Group A: is the control group, that received a placebo as a supplement. Group B: is the interventional group that supplemented with vitamin D tablets containing 2000 IU once time daily with a meal, for 3 months of intervention.

Concerning the laboratory investigations; vitamin D status was assessed by measuring the concentration of 25-hydroxyvitamin D (25(OH)D) in the children's serum. Levels of 25(OH)D were interpreted as deficiency (≤20 ng/ml or ≤50 nmol/L), insufficiency (21-29 ng/ml or 52.5-72.5 nmol/L), and sufficiency (30-100 ng/ml ng/ml or 75-250 nmol/L). The glycated hemoglobin levels are defined based on the control of diabetes, as good control (HbA1c\<7.8%), moderate control (HbA1c:7.8%-9.9%), and poor control (HbA1c\>9.9%).

2.5 Tools of Data Collection

Children's health assessment structure interview sheet was used to collect data. It was constructed by the researchers based upon relevant literature. The questionnaire consisted of three parts:

Part I: Children's socio-demographic characteristics This part was aimed to collect socio-demographic characteristics for both interventions, and control groups before the intervention such as age, gender, number of family members, and level of education.

Part II: Children's current health history It covered the history of the discovery of diabetes, duration of diabetes, type of insulin, family history of diabetes, and periodic test for diabetes. This part had been used before the intervention for both the intervention and control groups.

Part III: Children's laboratory investigations This part addressed HbA1c that was investigated and recorded before and after the interference for both interventions, and control groups. Additionally, vitamin D status was assessed and recorded before the intervention for both interventions, and control groups.

2.6 Statistical analysis Data was entered and statistically analyzed using a statistical package for social sciences (SPSS) version 26 database for windows 10. Descriptive statistics were used to summarize the socio-demographic characteristics of subjects. Numerical data like 25-(OH)D levels, and HbA1c, were presented as mean (SD) or median (IQR) based on their normality distribution. Categorical data were presented as frequency (percentage). The chi-square test was used for categorical data comparison. Analysis of quantitative data between two groups was done using unpaired t-test. Pearson correlation coefficients between continuous variables were used as a measure of association. A p-value \<0.05 was considered statistically significant.

Eligibility criteria: The eligibility criteria are:

Criteria for children with T1DM:

Inclusion criteria for children with T1DM:

* Children (4-14 years of age) of both genders, with a T1DM.
* Not on vitamin D Supplementation. Exclusion criteria for children with T1DM
* Age ≤ 4 or more than14 years old
* Patients with T2DM
* Children had received vitamin D supplements

Primary outcomes:
measure: Percent of HbA1c in children with T1DM for both intervention, and control groups.
timeFrame: Three Months
Secondary outcomes:
measure: Concentration of Vitamin D for both intervention, and control groups
timeFrame: Three Months
Other outcomes:
Locations:
city: Gaza City
country: Palestinian Territory, occupied
facility: Al-Rantisi pediatric hospital
Study officials:
affiliation: Department of Laboratory Medicine, Al Azhar University-Gaza, Gaza Strip, Palestine
name: Heba A Al Sarraj, PhD
role: STUDY_CHAIR
affiliation: Department of Laboratory Medicine, Al Azhar University-Gaza, Gaza Strip, Palestine
name: Ashraf J Shaqaliah, Master
role: STUDY_DIRECTOR
affiliation: Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia
name: Heba M Arafat, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of a Medical Laboratory Sciences, Faculty of Health Sciences, Islamic University of Gaza
name: Ohood M Shamallakh, Master
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of a Medical Laboratory Sciences, Faculty of Health Sciences, Islamic University of Gaza
name: Kholoud M Shamallakh, Master
role: PRINCIPAL_INVESTIGATOR
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