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

NCT ID: NCT02217553

Last Updated: 2014-08-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2014-06-30

Brief Summary

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

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.

Conditions

Blood Platelet Disorders; Vitamin D Deficiency

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Cholecalciferol

Intervention Type: DRUG

The study participants will receive 180 soft gel cholecalciferol capsules, to be taken 2 capsules once a day for 90 days

Interventions

Cholecalciferol

The study participants will receive 180 soft gel cholecalciferol capsules, to be taken 2 capsules once a day for 90 days

Intervention Type: DRUG

Other Intervention Names

Teorol

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: collaborator

Universitas Padjadjaran

OTHER

Sponsor Role: lead

Responsible Party

Mohammad Ghozali

Medical Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andre van der Ven, Professor

Role: STUDY_CHAIR

Radboud University Medical Center

Quirijn de Mast, Doctor

Role: STUDY_DIRECTOR

Radboud University Medical Center

Rudi Wisaksana, Doctor

Role: STUDY_DIRECTOR

Universitas Padjadjaran

Agnes R Indrati, Doctor

Role: STUDY_DIRECTOR

Universitas Padjadjaran

Locations

Klinik Teratai Hasan Sadikin General

Bandung, West Java, Indonesia

Countries

Indonesia

Related Links

http://www.fk.unpad.ac.id

Official web site of Faculty of Medicine, Universitas Padjadjaran

http://www.radboudumc.nl

Official web site of Radboud University Medical Center

Other Identifiers

1402001

Identifier Type: -

Identifier Source: org_study_id