Clinical trial NCT02750293: The Effect of Vitamin D Supplementation on Cardiovascular Risk Factors
Official title: The Effect of Vitamin D Supplementation on Cardiovascular Risk Factors in Subjects With Low Serum 25-hydroxyvitamin D Levels
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Vitamin D Deficiency
Keywords: vitamin D
blood pressure
serum lipids
glucose metabolism
muscle function
arterial stiffness
depression
psoriasis
sleep
bone density
Lead sponsor: University of Tromso
Sponsor class: OTHER
First posted: 2016-04-25
Enrollment: 411
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Six-hundred subjects with vitamin D deficiency will be randomized to vitamin D 3000 IU per day versus placebo for 4 months, with effects on cardiovascular risk factors as main endpoint

Detailed description: Vitamin D is a hormone with effects not only on the skeleton, but on most tissues in the body. Lack of vitamin D is associated with cardio-vascular disease (CVD) and type 2 diabetes, and also with risk factors for these diseases like hypertension, dyslipidemia, insulin resistance, and endothelial dysfunction. However, intervention studies with vitamin D have been inconclusive regarding diseases and risk factors. Most of these studies were done in white, Western populations in subjects fairly vitamin D sufficient, and accordingly, no benefits were to be expected. Also, in many studies the doses of vitamin D have been too low, and the studies underpowered. To firmly establish the role of vitamin D regarding CVD risk factors we will in the present study include 600 subjects with vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) \< 30 nmol/L) and randomize to high dose vitamin D (3000 IU per day) versus placebo for four months. The subjects will be recruited based on 25(OH)D measurements in the forthcoming 7th survey in the Tromsø study where more than 20 000 subjects are expected to attend. If our hypotheses are correct and the vitamin D supplement has a positive effect, this will be of great importance not only in countries with low sun exposure, but particularly for subjects in developing countries where vitamin D deficiency is highly prevalent.

Eligibility criteria: Inclusion Criteria:

* participated in The 7th survey in The Tromsø study
* vitamin D deficiency

Exclusion Criteria:

* primary hyperparathyroidism
* granulomatous disease
* reduced kidney function
* systolic blood pressure \> 174 mmHg
* diastolic blood pressure \> 104 mmHg
* diabetes
* renal stones last 5 years
* use of solarium on regular basis
* planned holidays in tropical areas
* clinical depression
* clinical signs of vitamin D deficiency (muscle weakness)
* use of vitamin D supplements
* serious illness

Primary outcomes:
measure: Change from baseline in systolic and diastolic blood pressure
timeFrame: 4 months
Secondary outcomes:
measure: Change from baseline in hand-grip, quadriceps and biceps muscle strength measured by hand held dynamometry .
timeFrame: 4 months
measure: Change from baseline in score on Becks Depression Inventory
timeFrame: 4 months
measure: Change from baseline in cognitive function evaluated with The Twelve Word Memory Test
timeFrame: 4 months
measure: Change from baseline in cognitive function evaluated with The Digit Symbol Coding Test
timeFrame: 4 months
measure: Change from baseline in cognitive function evaluated with The Tapping Test
timeFrame: 4 months
measure: Change from baseline in arterial stiffness and endothelial function evaluated with pulse wave velocity
timeFrame: 4 months
measure: Change from baseline in arterial stiffness and endothelial function evaluated with augmentation index (AIX)
timeFrame: 4 months
measure: Change from baseline in arterial stiffness and endothelial function evaluated with the subendocardial viability ratio (SEVR)
timeFrame: 4 months
measure: Change from baseline in number of subjects with nasal staphylococcus aureus colonization
timeFrame: 4 months
measure: Change from baseline in bone mass density measured with dual energy x-ray absorptiometry (DEXA) at the lumbar spine and hip
timeFrame: 4 months
measure: Change from baseline in the bone turnover marker serum type 1 procollagen (P1NP)
timeFrame: 4 months
measure: Change from baseline in the bone turnover marker serum collagen type 1 cross-linked C-telopeptide (CTX-1)
timeFrame: 4 months
measure: Change from baseline in serum marker of interferon-γ mediated macrophage activation
timeFrame: 4 months
measure: Change from baseline in serum vitamin B6 status.
timeFrame: 4 months
measure: Change from baseline in the glycosylation marker HbA1c
timeFrame: 4 months
measure: Change from baseline in the glycosylation marker the receptor for advanced glycosylation end products (s-RAGE)
timeFrame: 4 months
measure: Change from baseline in the glycosylation marker carboxy-methyllysine
timeFrame: 4 months
measure: Change from baseline in psoriasis Activity in subjects with psoriasis evaluated with the Self-Administered Psoriasis Area Severity Index (SAPASI)
timeFrame: 4 months
measure: Change from baseline in psoriasis Activity in subjects with psoriasis, evaluated with the Dermatological Life Quality Index (DLQI)
timeFrame: 4 months
measure: Change from baseline in psoriasis Activity in subjects with psoriasis, evaluated with the Psoriasis Area Severity Index (PASI)
timeFrame: 4 months
measure: Change from baseline in transcriptomic profile (mRNA) in adipose tissue biopsies
timeFrame: 4 months
measure: Change from baseline in number of subjects with nocturnal legg cramps
timeFrame: 4 months
measure: Change from baseline in sleep pattern evaluated with the Tromsø Study 7th Survey sleep pattern questionnaire
timeFrame: 4 months
measure: Change from baseline in the serum total cholesterol
timeFrame: 4 months
measure: Change from baseline in the serum HDL-cholesterol
timeFrame: 4 months
measure: Change from baseline in the serum LDL-cholesterol
timeFrame: 4 months
measure: Change from baseline in the serum triglycerides
timeFrame: 4 months
measure: Change from baseline in the serum Apolipoprotein A1
timeFrame: 4 months
measure: Change from baseline in the serum Apolipoprotein B,
timeFrame: 4 months
measure: Change from baseline in insulin resistance evaluated with the homeostasis model assessment (HOMA) index based on fasting serum glucose and serum insulin
timeFrame: 4 months
measure: Change from baseline in proteomic profile with relative quantification in adipose tissue biopsies with the use of Liquid chromatography mass spectrometry Technology (LC-MS/MS)
timeFrame: 4 months
measure: Change from baseline in metabolomic profile with relative quantification in adipose tissue biopsies with the use of Liquid chromatography mass spectrometry Technology (LC-MS/MS)
timeFrame: 4 months
Other outcomes:
Locations:
city: Tromsø
country: Norway
facility: University Hospital of North Norway
Study officials:
affiliation: University of Tromso
name: rolf Jorde, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jorde R, Kubiak J, Svartberg J, Fuskevag OM, Figenschau Y, Martinaityte I, Grimnes G. Vitamin D supplementation has no effect on cognitive performance after four months in mid-aged and older subjects. J Neurol Sci. 2019 Jan 15;396:165-171. doi: 10.1016/j.jns.2018.11.020. Epub 2018 Nov 17.