Vitamin D DeficiencyNCT02551835
Vitamin D Supplements on Markers for Cardiovascular Disease and Diabetes: an Individual Participant Data Meta-analysis
An observational study of Vitamin D Deficiency and Vitamin; Excess Vitamin D (Nutritional), run by Amsterdam UMC, location VUmc.
Trial summary
This meta-analysis will be conducted to study the effect on vitamin D supplements on markers for cardiovascular disease and diabetes using individual participant data from 12 RCTs. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Vitamin D Deficiency, Vitamin; Excess Vitamin D (Nutritional)
- How many people
- 2,945 participants
- Where
- No sites listed yet
- Study dates
- Apr 2015to Aug 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The participating RCTs are the Tromso IGT, Tromso OBESITY, Tromso BMD, Tromso CLAMP, Tromso DEPRESSION, Styrian Vitamin D Hypertension Trial, Paravit, Oosterwerff, Chel, Wicherts, UCC1, and UCC2 trials.
Who may be able to join
- Availability of quality bio-banked samples for uniform 25(OH)D re-measurement
- Prospective data on one or more of the outcomes
- Willingness to collaborate
Who cannot join
- Trials among pregnant women, children, or performed in patient populations.
About this study
Official title: The Effect of Vitamin D Supplementation on Markers for Cardiovascular Disease and Diabetes: an Individual Participant Data Meta-analysis of Randomized Controlled Trials
This meta-analysis will be conducted to study the effect on vitamin D supplements on markers for cardiovascular disease and diabetes using individual participant data from 12 RCTs. Given that previous data suggest that vitamin D supplementation might be most effective in those individuals with very low 25-hydroxyvitamin D (25(OH)D) and potentially harmful in those achieving very high levels after vitamin D supplementation, this meta-analyses will be performed in subgroups according 25(OH)D levels.
Read the detailed description
Large randomized controlled trials (RCTs) are currently on-going to evaluate non-skeletal effects of vitamin D supplementation in the general older population. The results of these studies can be expected in 2017 to 2020 and while they will report important data, they may still leave knowledge gaps on the effects of vitamin D on clinically relevant surrogate parameters in specific groups. Recent data indicate that the association of vitamin D status and outcome is U- or reverse J-shaped and may be modified by the presence of certain risk factors or genetic variations of the vitamin D receptor.
This work is part of the European Union-project 'Food-based solutions for eradication of vitamin D deficiency and health promotion throughout the life cycle' (ODIN). This individual patient meta-analysis of existing high quality vitamin D RCTs aims to evaluate whether there are beneficial or harmful vitamin D effects on surrogate parameters for clinical outcomes (i.e. blood pressure, lipids, parathyroid hormone (PTH), fasting blood glucose and glycated haemoglobin (HbA1c)). With data from almost 3000 randomized subjects from 12 RCTs that are available within this consortium, the investigators will have sufficient power to detect clinically relevant effects of vitamin D supplementation on risk factors for cardiovascular disease.
Subgroup analyses will investigate effect modifiers to evaluate whether certain groups of individuals experience pronounced or attenuated effects from vitamin D supplementation. Given that previous data suggest that vitamin D supplementation might be most effective in those individuals with very low 25(OH)D and potentially harmful in those achieving very high levels after vitamin D supplementation, this individual patient data meta-analyses will be performed in subgroups with serum 25(OH)D levels <30, 40, and 50 nmol/L and >100, 125 and 150 nmol/L. 25(OH)D levels will be re-measured to ensure comparability.
- Keywords
- ODIN, Meta-analysis, Cholecalciferol, 25(OH)D, Subgroup effects
- Medical subject headings
- Vitamin D Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Tromso Impaired Glucose Tolerance (IGT) study | RCT on 20000 IU vitamin D3/week versus placebo for 1 year among persons with impaired glucose tolerance and/or impaired fasting glucose. | |
| Tromso OBESITY study | RCT on 20000 or 40000 IU vitamin D3/week plus 500 mg calcium/day versus placebo plus 500 mg calcium/day for 1 year among persons with a high body mass index. | |
| Tromso Bone Mineral Density (BMD) study | RCT on 40000 IU vitamin D3/week plus 800 IU/day and 1000 mg calcium/day versus placebo plus 800 IU/day and 1000 mg calcium/day for 1 year among women with a low bone mineral density. | |
| Tromso CLAMP study | RCT on 40000 IU vitamin D3/week versus placebo for 6 months among persons with 25(OH)D values <42 nmol/L. | |
| Tromso DEPRESSION study | RCT on 40000 IU vitamin D3/week versus placebo for 6 months among persons with 25(OH)D values <55 nmol/L. | |
| Styrian Vitamin D Hypertension Trial | RCT on 2800 IU vitamin D3/day versus placebo for 8 weeks among persons a history of arterial hypertension and 25(OH)D values <75 nmol/L. | |
| Paravit study | RCT on 7000 IU vitamin D3/day versus placebo for 6 months among persons with a high body mass index and 25(OH)D values <50 nmol/L. | |
| Oosterwerff study | RCT on 1200 IU vitamin D3/day plus 500 mg calcium/day versus placebo plus 500 mg calcium/day for 16 weeks among non-western immigrants with pre-diabetes and 25(OH)D values <50 nmol/L. | |
| Chel study | RCT on 600 IU vitamin D3/day (or daily equivalent) versus placebo for 4 months among nursing home residents >70 years of age. | |
| Wicherts study | RCT on 800 IU vitamin D3/day versus 100,000 IU/3 months versus sunlight advice for 6 months among non-western immigrants with 25(OH)D values <25 nmol/L. | |
| University College Cork (UCC) 1 study | RCT on 200, 400, or 600 IU vitamin D3/day versus placebo for 22 weeks among persons > 63 years of age. | |
| UCC 2 study | RCT on 200, 400, or 600 IU vitamin D3/day versus placebo for 22 weeks among persons 20-40 years of age. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood pressure
Systolic and diastolic (Main outcome of cardiovascular markers)
Measured: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)
HbA1c
(Main outcome of diabetic markers)
Measured: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)
Secondary outcomes (9)
High-density lipoproteins (HDL) cholesterol
Measured: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)
Low-density lipoproteins (LDL) cholesterol
Measured: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)
Total cholesterol
Measured: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)
Triglycerides
Measured: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)
Parathyroid hormone (PTH)
Parathyroid hormone
Measured: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)
Fasting glucose
Measured: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)
Fasting insulin
Measured: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)
C-peptide
Measured: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)
Two-hour glucose
After oral glucose tolerance test
Measured: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2015 (estimated)
- Study startApr 2015
- Primary completionAug 2016 (estimated)
- Study completionAug 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Vitamin D DeficiencyStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Prospective
- Enrolment
- 2,945 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Collaborators
- European Union
- Responsible party
- Principal investigator, Karin Swart, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02551835
- Sponsor's protocol ID
- ODIN 8.3
- Status last verified
- Mar 2016
- First submitted
- 10 Sep 2015
- Last updated
- 2 Mar 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Swart KM, Lips P, Brouwer IA, Jorde R, Heymans MW, Grimnes G, Grubler MR, Gaksch M, Tomaschitz A, Pilz S, Eiriksdottir G, Gudnason V, Wamberg L, Rejnmark L, Sempos CT, Durazo-Arvizu RA, Dowling KG, Hull G, Skrabakova Z, Kiely M, Cashman KD, van Schoor NM. Effects of vitamin D supplementation on markers for cardiovascular disease and type 2 diabetes: an individual participant data meta-analysis of randomized controlled trials. Am J Clin Nutr. 2018 Jun 1;107(6):1043-1053. doi: 10.1093/ajcn/nqy078.
PubMed 29868916
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Vitamin D Supplementation on Markers for Cardiovascular Disease and Diabetes: an Individual Participant Data Meta-analysis of Randomized Controlled Trials
- ClinicalTrials.gov ID
- NCT02551835
- Acronym / sponsor ID
- ODIN 8.3
- Keywords
- ODIN, Meta-analysis, Cholecalciferol, 25(OH)D, Subgroup effects
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 2,945 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Collaborators
- European Union
- Study start
- Apr 2015
- Primary completion
- Aug 2016 (estimated)
- Study completion
- Aug 2016 (estimated)
- First posted
- 16 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This meta-analysis will be conducted to study the effect on vitamin D supplements on markers for cardiovascular disease and diabetes using individual participant data from 12 RCTs. Given that previous data suggest that vitamin D supplementation might be most effective in those individuals with very low 25-hydroxyvitamin D (25(OH)D) and potentially harmful in those achieving very high levels after vitamin D supplementation, this meta-analyses will be performed in subgroups according 25(OH)D levels.
Detailed description
Large randomized controlled trials (RCTs) are currently on-going to evaluate non-skeletal effects of vitamin D supplementation in the general older population. The results of these studies can be expected in 2017 to 2020 and while they will report important data, they may still leave knowledge gaps on the effects of vitamin D on clinically relevant surrogate parameters in specific groups. Recent data indicate that the association of vitamin D status and outcome is U- or reverse J-shaped and may be modified by the presence of certain risk factors or genetic variations of the vitamin D receptor.
This work is part of the European Union-project 'Food-based solutions for eradication of vitamin D deficiency and health promotion throughout the life cycle' (ODIN). This individual patient meta-analysis of existing high quality vitamin D RCTs aims to evaluate whether there are beneficial or harmful vitamin D effects on surrogate parameters for clinical outcomes (i.e. blood pressure, lipids, parathyroid hormone (PTH), fasting blood glucose and glycated haemoglobin (HbA1c)). With data from almost 3000 randomized subjects from 12 RCTs that are available within this consortium, the investigators will have sufficient power to detect clinically relevant effects of vitamin D supplementation on risk factors for cardiovascular disease.
Subgroup analyses will investigate effect modifiers to evaluate whether certain groups of individuals experience pronounced or attenuated effects from vitamin D supplementation. Given that previous data suggest that vitamin D supplementation might be most effective in those individuals with very low 25(OH)D and potentially harmful in those achieving very high levels after vitamin D supplementation, this individual patient data meta-analyses will be performed in subgroups with serum 25(OH)D levels <30, 40, and 50 nmol/L and >100, 125 and 150 nmol/L. 25(OH)D levels will be re-measured to ensure comparability.
Study design
- Time perspective
- Prospective
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| Tromso Impaired Glucose Tolerance (IGT) study | – | –RCT on 20000 IU vitamin D3/week versus placebo for 1 year among persons with impaired glucose tolerance and/or impaired fasting glucose. |
| Tromso OBESITY study | – | –RCT on 20000 or 40000 IU vitamin D3/week plus 500 mg calcium/day versus placebo plus 500 mg calcium/day for 1 year among persons with a high body mass index. |
| Tromso Bone Mineral Density (BMD) study | – | –RCT on 40000 IU vitamin D3/week plus 800 IU/day and 1000 mg calcium/day versus placebo plus 800 IU/day and 1000 mg calcium/day for 1 year among women with a low bone mineral density. |
| Tromso CLAMP study | – | –RCT on 40000 IU vitamin D3/week versus placebo for 6 months among persons with 25(OH)D values <42 nmol/L. |
| Tromso DEPRESSION study | – | –RCT on 40000 IU vitamin D3/week versus placebo for 6 months among persons with 25(OH)D values <55 nmol/L. |
| Styrian Vitamin D Hypertension Trial | – | –RCT on 2800 IU vitamin D3/day versus placebo for 8 weeks among persons a history of arterial hypertension and 25(OH)D values <75 nmol/L. |
| Paravit study | – | –RCT on 7000 IU vitamin D3/day versus placebo for 6 months among persons with a high body mass index and 25(OH)D values <50 nmol/L. |
| Oosterwerff study | – | –RCT on 1200 IU vitamin D3/day plus 500 mg calcium/day versus placebo plus 500 mg calcium/day for 16 weeks among non-western immigrants with pre-diabetes and 25(OH)D values <50 nmol/L. |
| Chel study | – | –RCT on 600 IU vitamin D3/day (or daily equivalent) versus placebo for 4 months among nursing home residents >70 years of age. |
| Wicherts study | – | –RCT on 800 IU vitamin D3/day versus 100,000 IU/3 months versus sunlight advice for 6 months among non-western immigrants with 25(OH)D values <25 nmol/L. |
| University College Cork (UCC) 1 study | – | –RCT on 200, 400, or 600 IU vitamin D3/day versus placebo for 22 weeks among persons > 63 years of age. |
| UCC 2 study | – | –RCT on 200, 400, or 600 IU vitamin D3/day versus placebo for 22 weeks among persons 20-40 years of age. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The participating RCTs are the Tromso IGT, Tromso OBESITY, Tromso BMD, Tromso CLAMP, Tromso DEPRESSION, Styrian Vitamin D Hypertension Trial, Paravit, Oosterwerff, Chel, Wicherts, UCC1, and UCC2 trials.
Key inclusion criteria (3 listed)
- Availability of quality bio-banked samples for uniform 25(OH)D re-measurement
- Prospective data on one or more of the outcomes
- Willingness to collaborate
Key exclusion criteria (1 listed)
- Trials among pregnant women, children, or performed in patient populations.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Blood pressure
Time frame: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)
Systolic and diastolic (Main outcome of cardiovascular markers)
HbA1c
Time frame: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)
(Main outcome of diabetic markers)
9 secondary outcomes
High-density lipoproteins (HDL) cholesterol
Time frame: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)
Low-density lipoproteins (LDL) cholesterol
Time frame: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)
Total cholesterol
Time frame: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)
Triglycerides
Time frame: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)
Parathyroid hormone (PTH)
Time frame: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)
Fasting glucose
Time frame: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)
Fasting insulin
Time frame: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)
C-peptide
Time frame: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)
Two-hour glucose
Time frame: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2016.
- Derived from this study: PubMed 29868916Swart KM, Lips P, Brouwer IA, Jorde R, Heymans MW, Grimnes G, Grubler MR, Gaksch M, Tomaschitz A, Pilz S, Eiriksdottir G, Gudnason V, Wamberg L, Rejnmark L, Sempos CT, Durazo-Arvizu RA, Dowling KG, Hull G, Skrabakova Z, Kiely M, Cashman KD, van Schoor NM. Effects of vitamin D supplementation on markers for cardiovascular disease and type 2 diabetes: an individual participant data meta-analysis of randomized controlled trials. Am J Clin Nutr. 2018 Jun 1;107(6):1043-1053. doi: 10.1093/ajcn/nqy078.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Vitamin D Deficiency and Vitamin; Excess Vitamin D (Nutritional), run by Amsterdam UMC, location VUmc.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood pressure (time frame: Participants were followed for the duration of the intervention period (range 8 weeks - 1 year, depending on the RCT in which they are participating)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02551835, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2016.