Effect of Atorvastatin on Subclinical Atherosclerosis

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

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).

Study Overview

• Status: Unknown
• Conditions: CMV
• Intervention / Treatment: Drug: Atorvastatin - placebo controlled clinical trial

Detailed Description

Extended description of the protocol, including more technical information

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Indonesia
  • Center Jakarta
    • Jakarta, Center Jakarta, Indonesia, 10340
      • Cipto Mangunkusumo General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Atorvastatin 20 mg; 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; 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; Other Names: Ator-Placebo
Placebo Comparator: Placebo 20 mg; 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; 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; Other Names: Ator-Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Dr Cipto Mangunkusumo General Hospital

Publications and helpful links

General Publications

• 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.

Helpful Links

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2019
• Primary Completion (Anticipated): July 15, 2020
• Study Completion (Anticipated): July 15, 2021

Study Registration Dates

• First Submitted: August 28, 2019
• First Submitted That Met QC Criteria: September 20, 2019
• First Posted (Actual): September 24, 2019

Study Record Updates

• Last Update Posted (Actual): January 29, 2020
• Last Update Submitted That Met QC Criteria: January 28, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: atherosclerosis; statin
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: 19-03-0272; KET-265/UN2.F1/ETIK (Registry Identifier: Ethical Approval)

Drug and device information, study documents

• 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