Effect of Atorvastatin on Subclinical Atherosclerosis

CMV Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04101136
• Other study ID #: 19-03-0272
• Secondary ID: KET-265/UN2.F1/E
• Status: Enrolling by invitation
• Phase: N/A
• Start date: September 30, 2019
• Est. completion date: July 15, 2021

Study information

• Verified date: January 2020
• Source: Dr Cipto Mangunkusumo General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

Extended description of the protocol, including more technical information

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 80
• Est. completion date: July 15, 2021
• Est. primary completion date: July 15, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 45 Years

Eligibility

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)

Related Conditions & MeSH terms

• Atherosclerosis
• CMV

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

Locations

Country	Name	City	State
Indonesia	Cipto Mangunkusumo General Hospital	Jakarta	Center Jakarta

Sponsors (1)

Lead Sponsor	Collaborator
Dr Cipto Mangunkusumo General Hospital

Country where clinical trial is conducted

Indonesia, 

References & Publications (1)

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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 ?nding from the index teeth is recorded per sextant of teeth.	(1) 0-week visit, (2) 48-week visit
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External 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.