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

NCT ID: NCT01683656

Last Updated: 2019-10-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2014-07-31

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.

Conditions

HIV; Atherosclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

niacin/laropiprant

Intervention Type: DRUG

ER Niacin/laropipant Placebo

ER niacin/laropiprant placebo p.m.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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).

Interventions

niacin/laropiprant

Intervention Type: 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).

Intervention Type: DRUG

Other Intervention Names

Tredaptive

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.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Geneva

OTHER

Sponsor Role: collaborator

Swiss National Science Foundation

OTHER

Sponsor Role: collaborator

Fondation Ernest Boninchi

OTHER

Sponsor Role: collaborator

Swiss Heart Foundation

OTHER

Sponsor Role: collaborator

Calmy Alexandra

OTHER

Sponsor Role: lead

Responsible Party

Calmy Alexandra

Head of HIV Unit

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Alexandra Calmy, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Geneva

Locations

University Hospital Basel

Basel, Canton of Basel-City, Switzerland

University Hospital Berne Inselspital

Bern, Canton of Bern, Switzerland

University Hospitals Genève

Geneva, Canton of Geneva, Switzerland

Kantonsspital St Gallen

Sankt Gallen, Canton of St. Gallen, Switzerland

CHUV Cantonal University Hospital Vaud

Lausanne, Canton of Vaud, Switzerland

University Hospital Zurich

Zurich, Canton of Zurich, Switzerland

EOC Ente Ospedaliero Cantonale, civico

Lugano, Canton Ticino, Switzerland

Countries

Switzerland

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Other Identifiers

NILACH 2012DR4097

Identifier Type: -

Identifier Source: org_study_id