The Effect of Vitamin D Supplementation on HIV-associated Platelet Hyperreactivity

August 15, 2014 updated by: Mohammad Ghozali, Universitas Padjadjaran
Platelets play pivotal role in atherosclerosis and acute cardiovascular events. Platelet hyperreactivity and increase platelet-monocyte aggregate (PMA) formation are found in HIV infected patients, which may contribute to the excess cardiovascular risk. Low level of vitamin D has been associated with the presence of cardiovascular diseases. The aim of our study is to determine the effect of vitamin D supplementation on platelet activation, platelet reactivity and platelet-leukocyte complex formation in asymptomatic HIV-infected patients treated with ART

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

  1. Study design A prospective intervention study. HIV-infected patients using ART and who come for follow-up at the Teratai HIV clinic will be asked to participate in the study. All study participants will receive vitamin D supplementation (soft gel capsule containing cholecalciferol 400 IU) to be consumed 2 soft gel capsules daily for three consecutive months. The effect on the platelet parameters specified above will be determined before start cholecalciferol supplementation and after three months.
  2. Duration of study Usually, 150 HIV-infected patients are treated with ART every week at the Teratai HIV clinic of the Hasan Sadikin Hospital Bandung Indonesia. Between half January 2014 and end of February 2014, 50 patients will be enrolled in this study. We hypothesize that this period is long enough to include 50 patients for the present study. Supplementation will take place between March and May and analysis will be done in June and July. A summary of duration of study is depicted in the study timeline.
  3. Study population The study population consists of adult HIV-infected patients treated with ART enrolled at HIV polyclinic at Hasan Sadikin General Hospital, Bandung, Indonesia.
  4. Sample size calculation Our sample size calculation is based on the primary outcome, which is the area under the curve (AUC) of the platelet reactivity curve with P-selectin (CD62P) as platelet activation marker and ADP as platelet agonist. In a cohort of Dutch HIV-infected patients we found a mean AUC of 2500 with an SD of 660. Assuming that a decrease in AUC of 2500 to 2100 upon supplementation of vitamin D is clinically relevant, a sample size of 23 would be sufficient using a paired design with α 0.05 and a power of 80%.

  5. Methods Study parameters/endpoints

    There are two study parameters applied in this study:

    1. Platelet reactivity, expressed as the membrane expression of the platelet activation markers CD62P (P-selectin) and fibrinogen binding to integrin αIIbβ3, to stimulation with increasing concentration of platelet agonists ADP.
    2. Platelet-monocyte complexes.

  6. Study procedures

    a. Enrolment of patients During a scheduled routine polyclinic visit, the treating internist will identify patients fulfilling inclusion criteria. He/she will explain the background and objectives of the study to the patient. In case patients opt to participate, the patient will then be asked to read and undersign the informed consent form.

    Venous blood (three tubes of 3 mL each) will then drawn for study purpose at enrolment and after three months supplementation for:

    1. 25-hydroxyvitamin D level (3 ml serum)
    2. Platelet assays as specified above (3 ml CTAD)
    3. Full blood count and CD4 cells (3 ml EDTA) In many instances, this will not require an extra venepuncture as blood is usually collected for planned blood analysis for routine clinical care during regular polyclinic visits.

    Measurements and analysis consist of 25-hydroxyvitamin D level, platelet reactivity, and platelet-monocyte complexes will be done when the patients participate in the study. The study participants will receive 180 soft gel cholecalciferol capsules, to be taken 2 capsules once a day for 90 days as stated above.

    As stated above, the second blood analysis will take place three months later after vitamin D supplementation is completed.

    b. Collection of blood samples for vitamin D level analysis As much as 3mL additional blood is withdrawn while applying venepuncture for routine CD4+ measurement. Collected blood is stored using red top serum tube without anticoagulant. This will take place at enrolment (day 0) and after 3 months vitamin D supplementation. Each day of blood withdrawal, the collected tubes are stored temporarily in wet-iced box prior transfer to laboratory for vitamin D analysis. At the end of the policlinic day, all tubes are transferred to the laboratory for serum separation. Then, separated serum is stored so 25-hydroxyvitamin D measurements can be done later. All samples are analysed for 25-hydroxyvitamin D measurements as well as other vitamin D metabolites such as free 25-hydroxyvitamin D measurements. Such analysis can not be done in Indonesia and therefore samples will be shipped to the Netherlands for this purpose.

    c. Collection of blood samples for platelet function analysis As specified under study parameters above, platelet function analysis can be performed from one 3mL citrate-anticoagulated blood tube. This will take place at enrolment (day 0) and after 3 months vitamin D supplementation. Each withdrawn blood from the patient, the tube is directly transferred to the laboratory for platelet function within 30 minutes.

    d. Full blood count and CD4 cell measurements These measurements are part of routine care and will be done in the routine haematological laboratory using 3 ml EDTA blood.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Indonesia
    • West Java
      • Bandung, West Java, Indonesia, 40161
        • Klinik Teratai Hasan Sadikin General

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • >18 years
  • Treated with suppressive first-line ART for at least 12 months
  • Compliant to ART and procedures of Teratai clinic
  • No signs or symptoms

Exclusion Criteria:

  • Use of aspirin or other platelet function inhibitors.
  • Any sign or symptom
  • Known active opportunistic infection
  • Active illicit drug users or any other comorbidity
  • History of failing ART or non-compliance.
  • Pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: vitamin D (cholecalciferol)
All study participants will receive vitamin D supplementation (soft gel capsule containing cholecalciferol 400 IU) to be consumed 2 soft gel capsules daily for three consecutive months. The effect on the platelet parameters specified above will be determined before start cholecalciferol supplementation and after three months.
Drug: Cholecalciferol
The study participants will receive 180 soft gel cholecalciferol capsules, to be taken 2 capsules once a day for 90 days
Other Names:
  • Teorol

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The effect of vitamin D supplementation on HIV-associated platelet hyperreactivity
Time Frame: Three months
Mean Fluorescence Intensity of the platelet reactivity curve before and after receiving vitamin D
Three months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
The effect of vitamin D supplementation in platelet-monocyte aggregate formation
Time Frame: three months
Mean fluorescence intensity of platelet-monocyte aggregate before and after vitamin D supplementation
three months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Universitas Padjadjaran

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Radboud University Medical Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Andre van der Ven, Professor, Radboud University Medical Center
  • Study Director: Quirijn de Mast, Doctor, Radboud University Medical Center
  • Study Director: Rudi Wisaksana, Doctor, Universitas Padjadjaran
  • Study Director: Agnes R Indrati, Doctor, Universitas Padjadjaran

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2013

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2014

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 12, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 13, 2014

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 15, 2014

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 18, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 15, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1402001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings