Clinical trial NCT01683656: ER Niacin/Laropiprant Impact on Cardiovascular Markers and Atheroprogression in HIV-infected Individuals on cART
Official title: ER Niacin/Laropiprant Impact on Cardiovascular Markers and Atheroprogression in HIV-infected Individuals on cART
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: HIV
Atherosclerosis
Keywords: HIV
Atherosclerosis
Niacin/laropiprant
HDL
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
Collaborators: name: University Hospital, Geneva
name: Swiss National Science Foundation
name: Fondation Ernest Boninchi
name: Swiss Heart Foundation
First posted: 2012-09-12
Enrollment: 4
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: change in mean common carotid intima-media thickness
timeFrame: 48 weeks
Secondary outcomes:
measure: Mean hs-CRP plasma concentration changes
timeFrame: 12, 24, 48 weeks
measure: Mean Total Cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, apolipoprotein, triglycerides, and apolipoprotein (apo) Al, B and E levels
timeFrame: 12, 24, 48 weeks
measure: Mean biomarkers of inflammatory process (fibrinogen, S-VCAM-1, adiponectin, CCL2, CCL3, d-dimer, IL-6, TNF-alpha, Lp-PLA2) changes
timeFrame: 12, 24, 48 weeks
measure: Clinical MACE: cardiovascular mortality, stroke, acute coronary syndromes, any cardiac arrhythmias, hospitalisation for cardiovascular causes, peripheral artery disease, revascularization.
timeFrame: one year
Other outcomes:
Locations:
city: Berne
country: Switzerland
facility: University Hospital Berne Inselspital
state: BE
city: Basel
country: Switzerland
facility: University Hospital Basel
state: BS
city: Geneva
country: Switzerland
facility: University Hospitals Genève
state: GE
city: St Gallen
country: Switzerland
facility: Kantonsspital St Gallen
state: SG
city: Lugano
country: Switzerland
facility: EOC Ente Ospedaliero Cantonale, civico
state: TI
city: Lausanne
country: Switzerland
facility: CHUV Cantonal University Hospital Vaud
state: VD
city: Zurich
country: Switzerland
facility: University Hospital Zurich
state: ZH
Study officials:
affiliation: University Hospital, Geneva
name: Alexandra Calmy, MD
role: PRINCIPAL_INVESTIGATOR
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