. 2023 Feb 28;24(5):4679. doi: 10.3390/ijms24054679

Table 3.

Overview of recent completed clinical trials treating participants with vitamin D.

Title (Year of Completion)	Design	Intervention/Treatment	Endpoints/Outcomes	Results	Conclusions
Short-term vascular effects and oxidative status of calcium and vitamin D supplementation of postmenopausal hypertensive black women NCT04255992 [104] (2020)	Double-arm, double-blind, randomized, and parallel clinical trial 22 participants	Patients with stable antihypertensive therapy for at least 3 months Calcium arm: 1000 mg calcium tablet per day for 8 weeks Vitamin D/calcium arm: 1000 mg/800UI of vitamin D/calcium tablet per day for 8 weeks	Primary: Change in 24 h BP profile from baseline to week 8 Secondary: Change in serum malondialdehyde concentration from baseline to week 8	Calcium vs. vitamin D/calcium arm: no significant differences in diurnal SBP reductions (4.7 [−2.5–10] vs. 4.7 [0.6–8.10] mmHg, p = 0.630) and HsCRP reductions (1.68 [0.43–5.58] vs. 1.46 [0.36–4.63] mg/L, p = 0.540). However, the vitamin D/calcium combination reduced uric acid levels significantly better than calcium alone (by 16 [9.63–24] vs. 11 [8–18] mg/L, p = 0.020). All values are given as median [interquartile range].	Supplementation with both calcium alone and calcium and vitamin D in postmenopausal hypertensive women is associated with a significant reduction of diurnal BP and inflammatory biomarkers.
Study to investigate the effects of vitamin D administration on plasma renin activity in patients with stable chronic heart failure (VitD-CHF) NCT01092130 [105] (2013)	Open-label, blinded-endpoint, randomized, prospective trial 101 participants	Patients treated with ACE-inhibitors or ARBs and BARBs Control arm: no additional medication for 6 weeks Intervention arm: 2000 IU vitamin D daily, for 6 weeks	Primary: plasma renin activity (PRA) after 6 weeks Secondary: evaluation of the effect of vitamin D on plasma values of additional markers of RAAS activity, on different markers of the vitamin D cascade, on plasma levels of NT-proBNP, on urinary levels of markers of glomerular and tubular damage, on extracellular matrix markers, and on NYHA-class. Safety endpoints were biochemical indices of kidney function and bone homeostasis	Significant increase in both 25(OH)D and 1,25(OH)₂D levels in the intervention group compared to control (80 [75–87] vs. 44 [39–49] nmol/L, p < 0.001 and 194 (179–211] vs.132 [121–143] nmol/L, p < 0.001, respectively) after 6 weeks. Significant decrease in both PRA and PRC in the intervention group compared to control (5.2 [2.9–9.5] vs. 7.3 [4.5–11.8] ng/mL, p = 0.002 and 55 [32–93] vs. 72 [47–111] ng/mL, p = 0.02, respectively) after 6 weeks. All values given as geometric means [95%CI].	Supplementation with dietary vitamin D₃ (2.000 IU/d) in CHF patients increased vitamin D levels and lowered both PRA and PRC effectively compared to control.
Physiologic interactions between the adrenal- and the parathyroid glands NCT02572960 [106] (2018)	Double-blind, placebo-controlled trial 81 participants	Patients with secondary hyperparathyroidism due to vitamin D deficiency Arm 1: Vitamin D₃ 70 µg/day for 12 weeks valsartan 80 mg/day for 2 weeks Arm 2: Vitamin D₃ 70 µg/day for 12 weeks placebo valsartan daily for 2 weeks Arm 3: Placebo vitamin D₃/day for 12 weeks valsartan 80 mg/day for 2 weeks Arm 4: Placebo vitamin D₃/day for 12 weeks placebo Valsartan daily for 2 weeks	Primary: Aldosterone at baseline and after 12 weeks of vitamin D₃ treatment Secondary: PTH at baseline and after 2 weeks of ARB treatment, arterial stiffness, 24 h BP, physiological parameters	Valsartan (ARB) reduced DBP by −5.0 [−8.8; −1.0) mmHg vs. −2.6 [−7.5; 3.7] mmHg in the placebo group (p < 0.05). SBP was not significantly different in both groups. Renin increased strongly compared to placebo (81.2 [44.3; 180.0]) vs. 1.35 [−23.2; 46.3] pg/mL, p < 0.001), while the aldosterone ratio decreased significantly from valsartan treatment (−126 [−253; −52] vs. −8 [−59; 15], p < 0.0001). An addition of vitamin D₃ had no further effect Vitamin D₃ supplementation reduced PTH by −3.1 [−9.4; 9.1]% vs. a 5.7 [−5.2; 23.8]% increase in the placebo group (p = 0.1). All values are given as median [interquartile range].	No effect of ARB treatment on PTH plasma concentration. No correlation between calcium homeostasis and RAAS. Vitamin D₃ supplementation reduced PTH, but did not affect BP, cardiac conduction, or the RAAS.
Effects of vitamin D on blood pressure and cardiovascular risk factors NCT02136771 [66,107] (2014)	Single-center, double-blind, placebo-controlled, parallel-group study	Hypertensive patients with 25-hydroxyvitamin D levels below 30 ng/mL Treatment arm: 2800 IU vitamin D₃ per day as oily drops for 8 weeks Placebo arm: Oily drops only as placebo for 8 weeks	Primary: 24-h systolic ambulatory blood pressure after 8 weeks Secondary: 24-h diastolic ambulatory blood pressure, plasma renin concentration, plasma aldosterone concentration, NT-pro-BNP, 24-h urinary albumin excretion, triglycerides, HDL-cholesterol	No significant reduction of 24 h SBP was observed (−0.4 [−2.8 to 1.9] mmHg, p = 0.712). Triglycerides increased significantly in the vitamin D group with a mean treatment of 17 [1–33] mg/dL (p = 0.013). A significant increase in 25(OH)D (mean treatment effect 11.5 [9.4–13.7] ng/mL: p < 0.001) and a significant decrease in PTH (−5.7 [−9.3 to −2.1] pg/mL; p = 0.003). All values given as mean [95%CI].	No significant effects of vitamin D supplementation on BP and several cardiovascular risk factors were shown; however, a significant increase in triglycerides was observed.
DAYLIGHT: Vitamin D therapy in individuals at high risk of hypertension NCT01240512 [108] (2017)	Double-blind, randomized, controlled trial 534 participants	Patients with 25-hydroxyvitamin D <25 ng/mL, SBP 120–159 mmHg, DBP ≤ 99 mmHg, no antihypertensive medication High dose arm: 4000 IU/d vitamin D₃ for 6 months Low dose arm: 400 IU/d vitamin D₃ for 6 months	Primary: change in 24 h SBP after 6 months Secondary: change in 24 h DBP, change in mean daytime and nighttime ambulatory systolic and diastolic blood pressure, change in mean clinic systolic and diastolic blood pressure, change in mean clinic pulse pressure, all after 6 months	There was no significant difference in the primary end point or in any of the secondary end points. No evidence of association between change in 25-hydroxyvitamin D and change in 24-h systolic blood pressure after 6 months.	Supplementation with vitamin D did not reduce BP in vitamin D deficient individuals with either prehypertension or stage 1 hypertension.
The VALIDATE-D study NCT01635062 [109] (2017)	Randomized, double-blinded, and placebo-controlled study 18 participants	Patients with treated type-two diabetes, normal blood pressure or stage 1 hypertension (treated or untreated), and normal kidney function Intervention arm: calcitriol (titrated up to 0.75 µg/d) for 3 weeks Placebo arm: placebo for 3 weeks	Primary: change in circulating RAS activity after 2 weeks Secondary: change in renal plasma flow and urinary protein excretion after 2 weeks	Increases in 1,25(OH)₂D (45.4 ± 18.2 to 61.8 ± 11.2 pg/mL, p = 0.03) with calcitriol administration vs. no change in the placebo group. No significant differences in PRA, serum or urinary aldosterone, baseline ang II-stimulated MAP, or basal and ang II-stimulated RPF between interventions was found. Values are given as mean ± SD.	Calcitriol raises 1,25(OH)₂D levels compared to placebo, but this has no significant effect on the change in circulating RAS activity or vascular hemodynamics.