ER Niacin/Laropiprant Impact on Cardiovascular Markers and Atheroprogression in HIV-infected Individuals on cART (NILACH)
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
HIV Atherosclerosis |
Drug: niacin/laropiprant Drug: Placebo |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | ER Niacin/Laropiprant Impact on Cardiovascular Markers and Atheroprogression in HIV-infected Individuals on cART |
- change in mean common carotid intima-media thickness [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]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.
- Mean hs-CRP plasma concentration changes [ Time Frame: 12, 24, 48 weeks ] [ Designated as safety issue: No ]
- Mean Total Cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, apolipoprotein, triglycerides, and apolipoprotein (apo) Al, B and E levels [ Time Frame: 12, 24, 48 weeks ] [ Designated as safety issue: No ]
- Mean biomarkers of inflammatory process (fibrinogen, S-VCAM-1, adiponectin, CCL2, CCL3, d-dimer, IL-6, TNF-alpha, Lp-PLA2) changes [ Time Frame: 12, 24, 48 weeks ] [ Designated as safety issue: No ]
- Clinical MACE: cardiovascular mortality, stroke, acute coronary syndromes, any cardiac arrhythmias, hospitalisation for cardiovascular causes, peripheral artery disease, revascularization. [ Time Frame: one year ] [ Designated as safety issue: No ]
| Enrollment: | 4 |
| Study Start Date: | August 2012 |
| Estimated Study Completion Date: | July 2014 |
| Estimated Primary Completion Date: | July 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: ER Niacin/laropipant
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
Other Name: Tredaptive
|
|
Placebo Comparator: ER Niacin/laropipant Placebo
ER niacin/laropiprant placebo p.m.
|
Drug: Placebo
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).
|
Eligibility| Ages Eligible for Study: | 40 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations| Switzerland | |
| University Hospital Berne Inselspital | |
| Berne, BE, Switzerland, 3010 | |
| University Hospital Basel | |
| Basel, BS, Switzerland, 4031 | |
| University Hospitals Genève | |
| Geneva, GE, Switzerland, 1211 | |
| Kantonsspital St Gallen | |
| St Gallen, SG, Switzerland, 9007 | |
| EOC Ente Ospedaliero Cantonale, civico | |
| Lugano, TI, Switzerland, 6903 | |
| CHUV Cantonal University Hospital Vaud | |
| Lausanne, VD, Switzerland, 1011 | |
| University Hospital Zurich | |
| Zurich, ZH, Switzerland | |
| Principal Investigator: | Alexandra Calmy, MD | University Hospitals Geneva |
More Information
Publications:
| Responsible Party: | Calmy Alexandra, Head of HIV Unit, University Hospital, Geneva |
| ClinicalTrials.gov Identifier: | NCT01683656 History of Changes |
| Other Study ID Numbers: | NILACH 2012DR4097 |
| Study First Received: | August 31, 2012 |
| Last Updated: | March 14, 2013 |
| Health Authority: | Switzerland: Swissmedic |
Keywords provided by University Hospital, Geneva:
|
HIV Atherosclerosis Niacin/laropiprant HDL |
Additional relevant MeSH terms:
|
Atherosclerosis Arteriosclerosis Arterial Occlusive Diseases Vascular Diseases Cardiovascular Diseases Niacin Nicotinic Acids Niacinamide Vasodilator Agents Cardiovascular Agents Therapeutic Uses |
Pharmacologic Actions Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Vitamin B Complex Vitamins Micronutrients Growth Substances Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on May 22, 2013