ER Niacin/Laropiprant Impact on Cardiovascular Markers and Atheroprogression in HIV-infected Individuals on cART

Study Overview
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Brief Summary
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HIV-infected patients are at increased risk for cardiovascular disease. Large investigations support an inverse correlation between HDL-C levels and coronary heart disease. Therefore a treatment lowering HDL-C such as niacin could reduce the risk of atheroprogression not only through its benefit in terms of lipid profile, but also by reducing atherosclerotic inflammation. The study aims at showing that a therapy targeting HDL-C increase in HIV-infected patients on suppressive cART has the potential for reducing subclinical atherosclerotic inflammation associated with HIV itself in HIV-individuals on cART. NILACH is a randomised, multicenter, double blind, placebo controlled, 48 weeks trial to test the effect of the newly marketed niacin/laropiprant on carotid intima-media thickness (IMT) in 90 subjects. Regimen 1: ER niacin/laropiprant 1g/20 mg for the first 4 weeks and 2g/40mg from week 5 to the end of the study (the titration aims to reduce adverse reactions) Regimen 2: ER niacin/laropiprant placebo p.m. The primary end point is the change in mean common carotid intima-media thickness from baseline and 48 weeks, compared between the niacin/laropiprant group and the placebo group. The proposed in vivo experiments should provide insights on the potential benefits of niacin treatment of cardiovascular disease in HIV patients. In addition, we will be able to further clarify the role of systemic inflammatory mediators in the development of early atherosclerosis of HIV-infected patients on antiretroviral therapy. Detection and treatment of non-infectious co-morbidities such as cardiovascular diseases have become essential for HIV-infected individuals exposed to lifelong antiretroviral therapy and go beyond mere management of opportunistic infections or virologic suppression.

Official Title
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ER Niacin/Laropiprant Impact on Cardiovascular Markers and Atheroprogression in HIV-infected Individuals on cART

Conditions
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HIV, Atherosclerosis

Intervention / Treatment
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* Drug: niacin/laropiprant
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients > 40 years; Women of childbearing potential must use two reliable contraceptive methods during the entire trial, from day 1 to one month after the end of the trial. Signing the study consent form; Stable cART since at least 3 months (ie no recent drug change); HIV-RNA below 100 copies for at least 6 months; HDL-cholesterol <1.29 mmol/l for men; <1.42 mmol/l for women Exclusion Criteria: Pregnancy or lactation; Congestive Heart Failure; Malignant Hypertension; Acute or chronic coronary artery diseases; Any known cardiac arrhythmias; Diabetes; Concomitant cancer, rheumatologic disease or inflammatory bowel diseases; Concomitant renal or hepatic disease: Creatinine above 150 micromol/L Transaminases above 5 times upper normal limit Prothrombin time (Quick) value below 50%; Prior intolerance to niacin therapy (reported in a medical report); Cyclosporine, anti-inflammatory drugs (other than aspirin) or cytokine therapy in concomitant intake; Abnormal thyroid function; Excessive consumption of alcohol; Known severe lactose intolerance.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ER Niacin/laropipant<br>ER niacin/laropiprant 1g/20 mg for the first 4 weeks and 2g/40mg from week 5 to the end of the study. | Drug: niacin/laropiprant<br> <br> * Other names: Tredaptive;|
| Placebo Comparator: ER Niacin/laropipant Placebo<br>ER niacin/laropiprant placebo p.m. | Drug: Placebo<br>* Procedures for the manufacturing and testing of the placebo are compiled in the IMP/study drug dossier and comply with local regulatory requirements (by GMP certified manufacturer).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in mean common carotid intima-media thickness | mean of maximal IMT value will be calculated over three cardiac cycles and for left and right carotid artery at baseline and week 48. The primary endpoint will be assessed by a single investigator in a blinded and anonymized fashion at cIMT Core Facility, Department of Medicine, Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada Responsible: Pr Jean-Claude Tardif. | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean hs-CRP plasma concentration changes |  | 12, 24, 48 weeks | 
| Mean Total Cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, apolipoprotein, triglycerides, and apolipoprotein (apo) Al, B and E levels |  | 12, 24, 48 weeks | 
| Mean biomarkers of inflammatory process (fibrinogen, S-VCAM-1, adiponectin, CCL2, CCL3, d-dimer, IL-6, TNF-alpha, Lp-PLA2) changes |  | 12, 24, 48 weeks | 
| Clinical MACE: cardiovascular mortality, stroke, acute coronary syndromes, any cardiac arrhythmias, hospitalisation for cardiovascular causes, peripheral artery disease, revascularization. |  | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Atherosclerosis, Niacin/laropiprant, HDL