Evaluating the effectiveness of using two Vitamin D Supplementation regimes to improve glucose tolerance in vitamin D deficient Sri Lankan adults: A preliminary open labelled phase IV randomised trial

INTERVENTION: Study setting – Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura Study population – Adults residing in Anuradhapura district Sri Lanka. Adults with impaired glucose tolerance (IGT) as per the WHO criteria (fasting plasma glucose (< 126 mg/dL, 7 mmol/L) and 2‐hour plasma glucose after a 75g of glucose load between 140 – 199 mg/dL (7.8 – 11.1 mmol/L) Intervention Group 1 ‐ 2,000 IU daily cholecalciferol (vitamin D3) for 24 weeks+ lifestyle modifications* Group 2 ‐ 60,000 IU per week cholecalciferol (vitamin D3) for 8 weeks, followed by 2,000 IU/day cholecalciferol (vitamin D3) for 16 weeks + lifestyle modifications* *‐lifestyle modifications include sun exposure, diet and level of physical activities Sun exposure ‐Exposing at least 25‐30% of body surface area (face, arms and legs) for direct sunlight without sunscreen daily for 30‐35 minutes between 10.00 am to 3.00 pm, Diet ‐ The dietary pattern of the participants will be assessed based on the data obtained at the baseline assessment through 3‐day food diary. Accordingly necessary dietary modification advices will be given based on food based dietary guidelines developed by Ministry of Health, Sri Lanka Level of Physical activities ‐ The advices will be provided based on the 2024 Guideline for the Primary Prevention of Stroke: A Guideline from the American Heart Association/American Stroke Association. Accordingly, the participants will be advised to engage in at least 150 minutes of moderate‐intensity physical activity, 75 minutes of vigorous‐intensity physical activity, or an equivalent combination per week and to avoid excessive time spent in sedentary behaviour (characterized by low energy expenditure while sitting, reclining, or lying while awake) Randomization – block randomization Block randomization will be performed after recruitment of the required sample size. Initially, participants will be ranked in descending order based on baseline serum vitamin D levels to ensure comparable baseline distribution between groups. Subsequently, participants will be divided into 10 blocks, each comprising four individuals. Within each block, two participants will be assigned to each group. Allocation within each block will be determined using randomly selected sequences. All possible allocation arrangements (e.g., 1‐1‐2‐2, 1‐2‐1‐2, 2‐2‐1‐1, 1‐2‐2‐1, 2‐1‐1‐2) will be written on paper chits. For each block, one chit will be randomly selected to determine the allocation sequence. After each selection, the chit will be returned to the pool to allow for random reuse in subsequent blocks. CONDITION: Vitamin D deficiency and impaired glucose tolerance PRIMARY OUTCOME: Changes in plasma glucose tolerance following vitamin D supplementation; Method ‐ assessment of plasma glucose level 2 hours after 75g oral glucose load (oral glucose tolerance test); [At the point of recruitment (baseline) and 24 weeks after the intervention (end of trial)]; INCLUSION CRITERIA: Adults (both males and females) aged 30‐50 years Normal body mass inde X18.5 – 22.9 kg/m² as per the South Asian cutoffs Vitamin D deficient (<20 ng/mL) or insufficient (21‐29 ng/mL) Impaired glucose tolerance as of the results of oral glucose tolerance test (fasting plasma glucose (< 126 mg/dL) and 2‐ hour plasma glucose 140 – 199 mg/dL), Adults who can understand written and verbal communications in Sinhala or English languages SECONDARY OUTCOME: Changes in plasma glucose, insulin, and insulin sensitivity; Method ‐ assessing fasting plasma glucose, serum insulin and HOMA‐IR score [At the point of recruitment and 24 weeks after (end of the intervention)]; Proportion achieving vitamin D sufficiency through two regimes after 10 weeks and 24 weeks of supplementation; Method ‐ calculating the percentage of participants who achieved the normal vitamin D levels [ At the point of recruitment and 24 weeks after (end of the intervention)]; Adherence to supplementation; Method ‐ Treatment diary will be given to the participants at each follow up visit along with the required number of pills until next visit (monthly). participants will be advised to submit the remaining pills. Adherence will be measured using the treatment diary and the remaining pill count [At every follow up visit (at the end of 4th, 8th, 10th, 16th, 20th and 24th week)]; Tolerability and adverse events; Method ‐ Assessing the treatment diary, detailed structured clinical assessment at follow up visits and laboratory investigation results in suspected events of vitamin D toxicity. [Treatment diary and clinical assessment ‐ at every follow up visit (at the end of 4th, 8th, 10th, 16th, 20th and 24th week); Laboratory assessment ‐ baseline, 10th week and 24th week]; Changes in diet, physical activity, and sun exposure; Method ; Diet ‐ 3 day food diary; Sun exposure ‐ 3 day sun exposure diary; Physical activity ‐ International physical activity questionnaire (IPAQ) short version [ Baseline, 10th and 24th week]; Changes in serum vitamin D levels following vitamin D supplementation Method ‐ assessment of serum vitamin D level [At the point of recruitment (baseline) and, 10 weeks and 24 weeks after the intervention]; Changes in serum vitamin D levels following vitamin D supplementation Method ‐ assessment of serum vitamin D level [At the point of recruitment (baseline) and, 10 weeks and 24 weeks after the intervention];