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

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

Resource links provided by NLM:

MedlinePlus related topics: Atherosclerosis HIV/AIDS

Drug Information available for: Niacin Niacinamide

U.S. FDA Resources

Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:

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.

Secondary Outcome Measures:

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 (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01683656

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

Sponsors and Collaborators

Calmy Alexandra

University Hospital, Geneva

Swiss National Science Foundation

Fondation Ernest Boninchi

Swiss Heart Foundation

Investigators


Principal Investigator:	Alexandra Calmy, MD	University Hospitals Geneva

More Information

Publications:

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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 Niacinamide Nicotinic Acids Hypolipidemic Agents	Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Vasodilator Agents Vitamin B Complex Vitamins Micronutrients Growth Substances Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 23, 2016

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