search
Back to results

Effect of Atorvastatin on Subclinical Atherosclerosis

Primary Purpose

CMV

Status
Unknown status
Phase
Not Applicable
Locations
Indonesia
Study Type
Interventional
Intervention
Atorvastatin - placebo controlled clinical trial
Sponsored by
Dr Cipto Mangunkusumo General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for CMV focused on measuring statin, atherosclerosis

Eligibility Criteria

20 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Ages between 20 to 45 years old
  • Using stable ART at least 1 year
  • Positive IgG CMV
  • Viral load HIV RNA <50 copies / ml

Exclusion Criteria:

  • Undergoing hepatitis C DAA therapy
  • Decompensated cirrhosis or acute liver failure
  • History of coronary artery disease
  • Diabetes mellitus
  • History of of brain infection, epilepsy, stroke
  • History of rhabdomyolysis or myopathy
  • Pregnant or breastfeeding
  • Severe depression
  • Using statin therapy in the past 6 weeks
  • History of statin hypersensitivity
  • Framingham Risk Score above 10% within LDL ≥130
  • Framingham Risk Score under 10% within LDL ≥160
  • Out of Periodontitis Index (Upper right molars, top series, upper left molars, lower right molars, bottom series, lower left molars)

Sites / Locations

  • Cipto Mangunkusumo General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Atorvastatin 20 mg

Placebo 20 mg

Arm Description

Study pharmacist will make code (A and B) for atorvastatin and placebo, then save the code in safe place. Pharmacist will record each subject as participant received A or B intervention.

The placebo tablets will be prepared by Cipto Mangunkusumo hospital pharmacist, were composed of starch and were similar to atorvastatin tablets in size, shape, and colour.

Outcomes

Primary Outcome Measures

Carotid intima medial tunica change
Numerical changes (in millimeter) between baseline and 48 weeks. Common Carotid Artery (CCA) intima media thickness measured by using B mode imaging system (Affiniti 70 series), equipped with a linear array transducer > 7 MHz with minimal compression (<10:1) and footprint of at least 3 cm. This procedure is operated by certified Cardiologist. Reference Siomva I. Intima-media thickness: appropriate evaluation and proper measurement, described. ESC. May 2015;15:21.

Secondary Outcome Measures

Flow mediated vasodilatation change
Numerical changes (in percentage) between baseline and 48 weeks FMD. Using a high-resolution ultrasound linear array transducer, longitudinal images of the right brachial artery (mostly 3-15 cm above the elbow) were recorded at the baseline and for 3 minutes after cuff deflation following suprasystolic compression (50 mmHg over the systolic blood pressure) of the right forearm for 5 minutes. This procedure is operated by certified cardiologist. Reference: Charakida M, Masi S, Luscher TF, Kastelein JJ, Deanfield JE.Assessment of atherosclerosis: the role of flow-mediated dilatation.Eur Heart J. 2010 Dec;31(23):2854-61
Liver fibrosis change
Numerical changes (in KPa) between baseline and 48 week. The measurement of liver stiffness which uses the velocity of shear waves that travel through the liver using the Fibroscan (Echosens) device. This procedure is operated by certified hepatologist.
Liver steatosis change
Numerical changes (in dB/m) between baseline and 48 weeks. The measurement of steatosis using the Fibroscan (Echosens) equipped with CAP software. dB/m. This procedure is operated by certified hepatologist.
Fasting lipid change
Numerical changes of fasting lipid profile consist of total cholesterol, LDL-C, HDL-C and triglyceride in mg/dL. Range of fasting is 8 - 10 hours. The test is located in Cipto Mangunkusumo Hospital or Prodia Laboratory Clinic.
Neurocognitive function change
Mean or median changes of neurocognitive function change. Neurologist will do supervision while subject do the test. The measurement tool is questionnaire named "neurocognitive test". This item will comprising several aspects: Trail making test Symbol digit modalities test Brief visuospatial memory test revised California verbal learning test II
Community Periodontal Index (CPI)
This Community Periodontal Index takes into consideration 10 teeth in the oral cavity i.e. 17, 16, 11, 26, 27, 37, 36, 31, 46 and 47 and subsequently evaluates the occurrence of gingival bleeding, presence of supra- and subgingival calculus, periodontal pockets with probing depths between 3.5-6.0 mm, as well as clinical attachment loss. This procedure done by dentist. CPI score: Score 0: health periodontal conditions Score 1: gingival bleeding on probing Score 2: calculus and bleeding Score 3: periodontal pocket 4-5 mm Score 4: periodontal pocket ≥6 mm Only the worst finding from the index teeth is recorded per sextant of teeth.
beta 2-microglobulin change
The numerical change of beta 2-microglobulin (in pg/mL) between 0-week visit and 48-week visit. This examination located in Indonesian Medical Education and Research Institute (IMERI) laboratory
Soluble CD14 change
The numerical change of sCD14 (in pg/mL) between 0-week visit and 48-week visit. This examination located in Indonesian Medical Education and Research Institute (IMERI) laboratory
ICAM-1 change
The numerical change of ICAM-1 (in pg/mL) between 0-week visit and 48-week visit. This examination located in Indonesian Medical Education and Research Institute (IMERI) laboratory
High Sensitivity C-Reactive Protein (hsCRP) change
The numerical change of hsCRP (in mg/L) between 0-week visit and 48-week visit. This examination located in Indonesian Medical Education and Research Institute (IMERI) laboratory
Vascular Cell Adhesion Molecule-1 (V CAM-1) change
The numerical change of V CAM-1 (in pg/mL) between 0-week visit and 48-week visit. This examination located in Indonesian Medical Education and Research Institute (IMERI) laboratory

Full Information

First Posted
August 28, 2019
Last Updated
January 28, 2020
Sponsor
Dr Cipto Mangunkusumo General Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT04101136
Brief Title
Effect of Atorvastatin on Subclinical Atherosclerosis
Official Title
Effect of Atorvastatin on Subclinical Atherosclerosis in Virally-suppressed HIV-infected Patients With CMV Seropositivity: a Randomized Double-blind Placebo-controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Unknown status
Study Start Date
September 30, 2019 (Actual)
Primary Completion Date
July 15, 2020 (Anticipated)
Study Completion Date
July 15, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dr Cipto Mangunkusumo General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Statin administration is supposed to reduce subclinical atherosclerosis by decreasing LDL cholesterol levels, possibly via lipid-independent anti-inflammatory effect. Its pleiotropic properties also adding beneficial effect against CMV infection. The investigators plan to study atorvastatin in virally- suppressed HIV-infected patients on stable ART with CMV seropositive and statin-naïve to evaluate the subclinical atherosclerosis changes assessed by carotid intima media thickness (CIMT).
Detailed Description
Extended description of the protocol, including more technical information

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
CMV
Keywords
statin, atherosclerosis

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Atorvastatin tablets in generic form. The placebo tablets will be prepared by Cipto Mangunkusumo hospital pharmacist, were composed of starch and were similar to atorvastatin tablets in size, shape, and colour. The participants will get the medication supply every month along with the refill of antiretroviral drugs. The drug and placebo tablets will be administered to patients by a staff member who are privy to the treatment. In the end of every month, each participant should return the unused pills every month.
Masking
ParticipantCare Provider
Masking Description
Subjects with undetectable HIV-RNA, positive anti-CMV, having Framingham Risk Score above 10% with LDL < 130 or under 10% with LDL <160 will undergo thorough medical history and anthropometric examination as the initial data. Patient will be seen for regular clinical follow up as standard of care in the clinic (monthly/ bimonthly). Follow up visit will include clinical and laboratory procedure. At week 24, blood collection procedures and neurocognitive examination procedures will be repeated. At week 48, blood collection procedures, CIMT, FMD, transient elastography with CAP, and neurocognitive examination procedures will be repeated.
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Atorvastatin 20 mg
Arm Type
Active Comparator
Arm Description
Study pharmacist will make code (A and B) for atorvastatin and placebo, then save the code in safe place. Pharmacist will record each subject as participant received A or B intervention.
Arm Title
Placebo 20 mg
Arm Type
Placebo Comparator
Arm Description
The placebo tablets will be prepared by Cipto Mangunkusumo hospital pharmacist, were composed of starch and were similar to atorvastatin tablets in size, shape, and colour.
Intervention Type
Drug
Intervention Name(s)
Atorvastatin - placebo controlled clinical trial
Other Intervention Name(s)
Ator-Placebo
Intervention Description
The participants will get the medication supply every month along with the refill of antiretroviral drugs. The drug and placebo tablets will be administered to patients by a staff member who are privy to the treatment. In the end of every month, each participant should return the unused pills every month
Primary Outcome Measure Information:
Title
Carotid intima medial tunica change
Description
Numerical changes (in millimeter) between baseline and 48 weeks. Common Carotid Artery (CCA) intima media thickness measured by using B mode imaging system (Affiniti 70 series), equipped with a linear array transducer > 7 MHz with minimal compression (<10:1) and footprint of at least 3 cm. This procedure is operated by certified Cardiologist. Reference Siomva I. Intima-media thickness: appropriate evaluation and proper measurement, described. ESC. May 2015;15:21.
Time Frame
(1) 0-week visit, (2) 48-week visit
Secondary Outcome Measure Information:
Title
Flow mediated vasodilatation change
Description
Numerical changes (in percentage) between baseline and 48 weeks FMD. Using a high-resolution ultrasound linear array transducer, longitudinal images of the right brachial artery (mostly 3-15 cm above the elbow) were recorded at the baseline and for 3 minutes after cuff deflation following suprasystolic compression (50 mmHg over the systolic blood pressure) of the right forearm for 5 minutes. This procedure is operated by certified cardiologist. Reference: Charakida M, Masi S, Luscher TF, Kastelein JJ, Deanfield JE.Assessment of atherosclerosis: the role of flow-mediated dilatation.Eur Heart J. 2010 Dec;31(23):2854-61
Time Frame
(1) 0-week visit, (2) 48-week visit
Title
Liver fibrosis change
Description
Numerical changes (in KPa) between baseline and 48 week. The measurement of liver stiffness which uses the velocity of shear waves that travel through the liver using the Fibroscan (Echosens) device. This procedure is operated by certified hepatologist.
Time Frame
(1) 0-week visit, (2) 48-week visit
Title
Liver steatosis change
Description
Numerical changes (in dB/m) between baseline and 48 weeks. The measurement of steatosis using the Fibroscan (Echosens) equipped with CAP software. dB/m. This procedure is operated by certified hepatologist.
Time Frame
(1) 0-week visit, (2) 48-week visit
Title
Fasting lipid change
Description
Numerical changes of fasting lipid profile consist of total cholesterol, LDL-C, HDL-C and triglyceride in mg/dL. Range of fasting is 8 - 10 hours. The test is located in Cipto Mangunkusumo Hospital or Prodia Laboratory Clinic.
Time Frame
(1) 0-week visit, (2) 48-week visit
Title
Neurocognitive function change
Description
Mean or median changes of neurocognitive function change. Neurologist will do supervision while subject do the test. The measurement tool is questionnaire named "neurocognitive test". This item will comprising several aspects: Trail making test Symbol digit modalities test Brief visuospatial memory test revised California verbal learning test II
Time Frame
(1) 0-week visit, (2) 24-week visit, (3) 48-week visit
Title
Community Periodontal Index (CPI)
Description
This Community Periodontal Index takes into consideration 10 teeth in the oral cavity i.e. 17, 16, 11, 26, 27, 37, 36, 31, 46 and 47 and subsequently evaluates the occurrence of gingival bleeding, presence of supra- and subgingival calculus, periodontal pockets with probing depths between 3.5-6.0 mm, as well as clinical attachment loss. This procedure done by dentist. CPI score: Score 0: health periodontal conditions Score 1: gingival bleeding on probing Score 2: calculus and bleeding Score 3: periodontal pocket 4-5 mm Score 4: periodontal pocket ≥6 mm Only the worst finding from the index teeth is recorded per sextant of teeth.
Time Frame
(1) 0-week visit, (2) 48-week visit
Title
beta 2-microglobulin change
Description
The numerical change of beta 2-microglobulin (in pg/mL) between 0-week visit and 48-week visit. This examination located in Indonesian Medical Education and Research Institute (IMERI) laboratory
Time Frame
(1) 0-week visit, (2) 48-week visit
Title
Soluble CD14 change
Description
The numerical change of sCD14 (in pg/mL) between 0-week visit and 48-week visit. This examination located in Indonesian Medical Education and Research Institute (IMERI) laboratory
Time Frame
(1) 0-week visit, (2) 48-week visit
Title
ICAM-1 change
Description
The numerical change of ICAM-1 (in pg/mL) between 0-week visit and 48-week visit. This examination located in Indonesian Medical Education and Research Institute (IMERI) laboratory
Time Frame
(1) 0-week visit, (2) 48-week visit
Title
High Sensitivity C-Reactive Protein (hsCRP) change
Description
The numerical change of hsCRP (in mg/L) between 0-week visit and 48-week visit. This examination located in Indonesian Medical Education and Research Institute (IMERI) laboratory
Time Frame
(1) 0-week visit, (2) 48-week visit
Title
Vascular Cell Adhesion Molecule-1 (V CAM-1) change
Description
The numerical change of V CAM-1 (in pg/mL) between 0-week visit and 48-week visit. This examination located in Indonesian Medical Education and Research Institute (IMERI) laboratory
Time Frame
(1) 0-week visit, (2) 48-week visit

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Ages between 20 to 45 years old Using stable ART at least 1 year Positive IgG CMV Viral load HIV RNA <50 copies / ml Exclusion Criteria: Undergoing hepatitis C DAA therapy Decompensated cirrhosis or acute liver failure History of coronary artery disease Diabetes mellitus History of of brain infection, epilepsy, stroke History of rhabdomyolysis or myopathy Pregnant or breastfeeding Severe depression Using statin therapy in the past 6 weeks History of statin hypersensitivity Framingham Risk Score above 10% within LDL ≥130 Framingham Risk Score under 10% within LDL ≥160 Out of Periodontitis Index (Upper right molars, top series, upper left molars, lower right molars, bottom series, lower left molars)
Facility Information:
Facility Name
Cipto Mangunkusumo General Hospital
City
Jakarta
State/Province
Center Jakarta
ZIP/Postal Code
10340
Country
Indonesia

12. IPD Sharing Statement

Citations:
PubMed Identifier
29067253
Citation
Chastain DB, Stover KR, Riche DM. Evidence-based review of statin use in patients with HIV on antiretroviral therapy. J Clin Transl Endocrinol. 2017 Feb 22;8:6-14. doi: 10.1016/j.jcte.2017.01.004. eCollection 2017 Jun.
Results Reference
result
Links:
URL
https://www.ncbi.nlm.nih.gov/pubmed/29067253
Description
Chastain DB, Kayl RS, Daniel MR. Evidence-based review of statin use in patients with HIV on antiretroviral therapy. J Clin Transl Endocrinol. 2017;8:6-14.

Learn more about this trial

Effect of Atorvastatin on Subclinical Atherosclerosis

We'll reach out to this number within 24 hrs