Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    The effect of oral Vitamin D supplementation on endothelial function, vascular inflammation, oxidative stress and insulin sensitivity in patients with impaired fasting glucose: A randomised, double blinded, placebo controlled trial

    Summary
    EudraCT number
    		 2014-002766-73
    Trial protocol
    		 GB  
    Global end of trial date
    23 Jan 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    22 Jun 2022
    First version publication date
    22 Jun 2022
    Other versions
    Summary report(s)
    		 Vitamin-D justification for no results

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    PHT/2014/44
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Portsmouth Hospitals NHS Trust
    Sponsor organisation address
    Queen Alexandra Hospital, Portsmouth, United Kingdom, PO6 3LY
    Public contact
    Linda Harndahl , Portsmouth Hospitals NHS Trust, 0044 2392286236, Research.Office@porthosp.nhs.uk
    Scientific contact
    Michael Cummings, Portsmouth Hospitals NHS Trust, 0044 2392286000 , michael.cummings@porthosp.nhs.uk
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    09 Apr 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    13 Oct 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Jan 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study is to examine whether Vitamin D3 3,200 IU supplementation in patients with impaired fasting glucose has an effect on: reduction of the VCAM-1 marker (vascular circulating adhesion molecule-1) in blood.
    Protection of trial subjects
    The study was conducted in compliance with the Good Clinical Practice (GCP) guidelines, MHRA, REC approved protocol; study site local requirements to ensure the safety of trial participants. Vitamin D3 is a medication used to treat Vitamin D deficiency in the adults. Uncommon (>1/1000, <1/100) undesirable effects of Vitamin D3 include raised blood calcium levels and raised excretion of calcium in the urine. The dose of Vitamin D3 used in this study is safe and well within the Tolerable Upper Intake Level of 4000 IU/day and extremely unlikely to cause raised calcium levels and complications associated with this. Nonetheless, a system for assessing and reporting of adverse events will be set up to monitor the safety of participants. The exclusion criteria of our study ensure that patients with conditions and on treatments that could increase the risk of Vitamin D side effects are excluded from participation.Vitamin D3 rarely (>1/10 000, <1/1000) causes itching, rash and hives. Vitamin D3 and placebo capsules contain Arachis (peanut) oil that can cause allergic reaction in people with peanut and soya allergy. Patients with peanut and soya allergy will therefore be excluded from participation. All study participants will be made aware of the risks/precautions in a patient information leaflet.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Oct 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 46
    Worldwide total number of subjects
    46
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    24
    From 65 to 84 years
    22
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants were identified through routine screening by the clinical team at the Diabetes center. Local GP practices also carried out routine screening and referred eligible participants to the recruiting site. The search consisted of identifying participants with impaired fasting glucose.

    Pre-assignment
    Screening details
    		 Informed consent & participant capacity were assessed by the Principal investigator. Blood samples (11-15ml) will have been taken during the screening visit on participants having fasted overnight before the visit (instructions for fasting were provided on the participant information sheet - PIS). Clinical assessment including ECGs were done.

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    the identity of the placebo and active drug was appropriately concealed to the investigator team and participants of the study. These were over-encapsulated.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Arm B
    Arm description
    		 Participants in Arm B received placebo manufactured with appearance identical to the Fultium D3 3,200 IU capsules (Investigational Medicinal Product - IMP). The study IMP for the whole duration of the trial will be dispensed after the 1st study visit by the Pharmacy in Queen Alexandra Hospital, Portsmouth, UK. The IMP was to be taken by the participants orally one capsule orally once a day for 12 weeks (84 days).
    Arm type
    		 Placebo

    Investigational medicinal product name
    Manufactured matched placebo identical to the Fultium D3 3,200 IU capsules
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    One capsule orally once a day for 12 weeks (84 days)

    Arm title
    		 Arm A
    Arm description
    		 Participants in Arm A received Investigational Medicinal Product (IMP) Fultium D3 3,200 IU capsules. The study IMP for the whole duration of the trial will be dispensed after the 1st study visit by the Pharmacy in Queen Alexandra Hospital, Portsmouth, UK. The IMP was to be taken by the participants orally one capsule orally once a day for 12 weeks (84 days).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Colecalciferol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    One capsule containing 3,200 IU of colecalciferol daily

    Number of subjects in period 1
    		Arm B Arm A
    Started
    23
    23
    Completed
    23
    23

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Arm B
    Reporting group description
    		 Participants in Arm B received placebo manufactured with appearance identical to the Fultium D3 3,200 IU capsules (Investigational Medicinal Product - IMP). The study IMP for the whole duration of the trial will be dispensed after the 1st study visit by the Pharmacy in Queen Alexandra Hospital, Portsmouth, UK. The IMP was to be taken by the participants orally one capsule orally once a day for 12 weeks (84 days).

    Reporting group title
    Arm A
    Reporting group description
    		 Participants in Arm A received Investigational Medicinal Product (IMP) Fultium D3 3,200 IU capsules. The study IMP for the whole duration of the trial will be dispensed after the 1st study visit by the Pharmacy in Queen Alexandra Hospital, Portsmouth, UK. The IMP was to be taken by the participants orally one capsule orally once a day for 12 weeks (84 days).

    Reporting group values
    		 Arm B Arm A Total
    Number of subjects
    		 23 23 46
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 61.13 ( 8.83 ) 60.56 ( 9.85 ) -
    Gender categorical
    Units: Subjects
        Female
    		 15 16 31
        Male
    		 8 7 15

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Arm B
    Reporting group description
    		 Participants in Arm B received placebo manufactured with appearance identical to the Fultium D3 3,200 IU capsules (Investigational Medicinal Product - IMP). The study IMP for the whole duration of the trial will be dispensed after the 1st study visit by the Pharmacy in Queen Alexandra Hospital, Portsmouth, UK. The IMP was to be taken by the participants orally one capsule orally once a day for 12 weeks (84 days).

    Reporting group title
    Arm A
    Reporting group description
    		 Participants in Arm A received Investigational Medicinal Product (IMP) Fultium D3 3,200 IU capsules. The study IMP for the whole duration of the trial will be dispensed after the 1st study visit by the Pharmacy in Queen Alexandra Hospital, Portsmouth, UK. The IMP was to be taken by the participants orally one capsule orally once a day for 12 weeks (84 days).

    Primary: Endothlial activation marker VCAM-1

    		 Close Top of page
    End point title
    		 Endothlial activation marker VCAM-1
    End point description
    The relative change of endothelial activation marker VCAM-1 was the absolute change on logarithmic scale before and after the IMP or placebo.
    End point type
    Primary
    End point timeframe
    12 weeks
    End point values
    		 Arm B Arm A
    Number of subjects analysed
    21
    23
    Units: ng/ml
        number (not applicable)
    21
    23
    Statistical analysis title
    		 Analysis for change in vcam1
    Statistical analysis description
    Test for difference in change between vitamin d and placebo arm
    Comparison groups
    Arm B v Arm A
    Number of subjects included in analysis
    44
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.73 [1]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.012
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.061
         upper limit
    		 0.086
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0368
    Notes
    [1] - Two sided t-test for difference in absolute change between placebo and vitamin-D arms

    Secondary: Change in Insulin sensitivity

    		 Close Top of page
    End point title
    		 Change in Insulin sensitivity
    End point description
    Metabolic markers insulin resistance (HOMA-B) was calculated from an average of three measurements of fasting glucose and insulin (RIA).
    End point type
    Secondary
    End point timeframe
    12 weeks
    End point values
    		 Arm B Arm A
    Number of subjects analysed
    23
    23
    Units: NA
        number (not applicable)
    23
    23
    Statistical analysis title
    		 Analysis for change in insulin sensitivity
    Statistical analysis description
    Two sided t test for changes in insulin sensitivity
    Comparison groups
    Arm A v Arm B
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.64
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.53
         upper limit
    		 2.205
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.422

    Secondary: 8-iso-Prostaglandin F2a

    		 Close Top of page
    End point title
    		 8-iso-Prostaglandin F2a
    End point description
    8-iso-Prostaglandin F2a activity was used as one of oxidative stress markers.
    End point type
    Secondary
    End point timeframe
    12 weeks
    End point values
    		 Arm B Arm A
    Number of subjects analysed
    23
    23
    Units: pg/ml
        number (not applicable)
    23
    23
    Statistical analysis title
    		 Comparison of change in id 8 porstagl between arms
    Comparison groups
    Arm B v Arm A
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.267
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    19366.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15412.99
         upper limit
    		 54146.28
    Variability estimate
    Standard error of the mean
    Dispersion value
    17221.55

    Secondary: Cyclic Glycerylmonophosphate

    		 Close Top of page
    End point title
    		 Cyclic Glycerylmonophosphate
    End point description
    Cyclic Glycerylmonophosphate (cGMP) was one of the oxidative stress markers used in the study.
    End point type
    Secondary
    End point timeframe
    12 weeks
    End point values
    		 Arm B Arm A
    Number of subjects analysed
    21
    23
    Units: pmol/ml
        number (not applicable)
    21
    23
    Statistical analysis title
    		 Comparison of change in cGMP between arms
    Comparison groups
    Arm B v Arm A
    Number of subjects included in analysis
    44
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.053
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.797
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.605
         upper limit
    		 0.11
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4

    Secondary: Total oxidised glutathione ratio

    		 Close Top of page
    End point title
    		 Total oxidised glutathione ratio
    End point description
    End point type
    Secondary
    End point timeframe
    12 weeks
    End point values
    		 Arm B Arm A
    Number of subjects analysed
    23
    23
    Units: NA
        number (not applicable)
    23
    23
    No statistical analyses for this end point

    Secondary: Highly sensitive C-reactive protein

    		 Close Top of page
    End point title
    		 Highly sensitive C-reactive protein
    End point description
    Highly sensitive C-reactive protein (hsCRP ) is one of the markers of vascular inflammation.
    End point type
    Secondary
    End point timeframe
    12 weeks
    End point values
    		 Arm B Arm A
    Number of subjects analysed
    23
    23
    Units: mg/l
        number (not applicable)
    23
    23
    Statistical analysis title
    		 Comparison of change in hscrp between arms
    Comparison groups
    Arm B v Arm A
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.63
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.502
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.611
         upper limit
    		 2.616
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.046

    Secondary: Albumin:Creatinine ratio

    		 Close Top of page
    End point title
    		 Albumin:Creatinine ratio
    End point description
    Albumin: creatinine ratio is one of the markers of vascular inflammation.
    End point type
    Secondary
    End point timeframe
    12 weeks
    End point values
    		 Arm B Arm A
    Number of subjects analysed
    23
    23
    Units: NA
        number (not applicable)
    23
    23
    Statistical analysis title
    		 Analysis for change in acr
    Statistical analysis description
    All low values are assigned the value 0.00001 as per instructions
    Comparison groups
    Arm B v Arm A
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.87
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.906
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.286
         upper limit
    		 1.105
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.592

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Until end of trial 23/01/2017
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 No coding performed
    Dictionary version
    0
    Reporting groups
    Reporting group title
    All participants
    Reporting group description
    		 -

    Serious adverse events
    		 All participants
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 44 (2.27%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Surgical and medical procedures
    Surgery
    Additional description: Admitted for elective spinal surgery for spinal stenosis. Discharged on day 3 post admission on 30/07/16. Participant informed PI of date for elective surgery on 08/07/16 and of discharge on 05/08/16
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 All participants
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1 / 44 (2.27%)
    Cardiac disorders
    Vasovagal fainting episode
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences all number
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Mon Apr 29 16:24:48 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA