Effect of Atorvastatin on Subclinical Atherosclerosis

Study Overview
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Brief Summary
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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
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Extended description of the protocol, including more technical information

Official Title
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Effect of Atorvastatin on Subclinical Atherosclerosis in Virally-suppressed HIV-infected Patients With CMV Seropositivity: a Randomized Double-blind Placebo-controlled Trial

Conditions
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CMV

Intervention / Treatment
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* Drug: Atorvastatin - placebo controlled clinical trial


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Atorvastatin 20 mg<br>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. | Drug: Atorvastatin - placebo controlled clinical trial<br>* 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<br>* Other names: Ator-Placebo;|
| Placebo Comparator: Placebo 20 mg<br>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. | Drug: Atorvastatin - placebo controlled clinical trial<br>* 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<br>* Other names: Ator-Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | (1) 0-week visit, (2) 48-week visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | (1) 0-week visit, (2) 48-week visit | 
| 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. | (1) 0-week visit, (2) 48-week visit | 
| 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. | (1) 0-week visit, (2) 48-week visit | 
| 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. | (1) 0-week visit, (2) 48-week visit | 
| 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 | (1) 0-week visit, (2) 24-week visit, (3) 48-week visit | 
| 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. | (1) 0-week visit, (2) 48-week visit | 
| 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 | (1) 0-week visit, (2) 48-week visit | 
| 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 | (1) 0-week visit, (2) 48-week visit | 
| 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 | (1) 0-week visit, (2) 48-week visit | 
| 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 | (1) 0-week visit, (2) 48-week visit | 
| 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 | (1) 0-week visit, (2) 48-week visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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statin, atherosclerosis