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

October 7, 2019 updated by: Calmy Alexandra

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

4

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
    • BE
      • Berne, BE, Switzerland, 3010
        • University Hospital Berne Inselspital
    • BS
      • Basel, BS, Switzerland, 4031
        • University Hospital Basel
    • GE
      • Geneva, GE, Switzerland, 1211
        • University Hospitals Genève
    • SG
      • St Gallen, SG, Switzerland, 9007
        • Kantonsspital St Gallen
    • TI
      • Lugano, TI, Switzerland, 6903
        • EOC Ente Ospedaliero Cantonale, civico
    • VD
      • Lausanne, VD, Switzerland, 1011
        • CHUV Cantonal University Hospital Vaud
    • ZH
      • Zurich, ZH, Switzerland
        • University Hospital Zurich

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
change in mean common carotid intima-media thickness
Time Frame: 48 weeks
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
Time Frame
Mean hs-CRP plasma concentration changes
Time Frame: 12, 24, 48 weeks
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
Time Frame: 12, 24, 48 weeks
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
Time Frame: 12, 24, 48 weeks
12, 24, 48 weeks
Clinical MACE: cardiovascular mortality, stroke, acute coronary syndromes, any cardiac arrhythmias, hospitalisation for cardiovascular causes, peripheral artery disease, revascularization.
Time Frame: one year
one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Calmy Alexandra

Collaborators

University Hospital, Geneva
Swiss National Science Foundation
Swiss Heart Foundation
Fondation Ernest Boninchi

Investigators

  • Principal Investigator: Alexandra Calmy, MD, University Hospital, Geneva

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2012

Primary Completion (ACTUAL)

July 1, 2014

Study Completion (ACTUAL)

July 1, 2014

Study Registration Dates

First Submitted

August 31, 2012

First Submitted That Met QC Criteria

September 7, 2012

First Posted (ESTIMATE)

September 12, 2012

Study Record Updates

Last Update Posted (ACTUAL)

October 8, 2019

Last Update Submitted That Met QC Criteria

October 7, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NILACH 2012DR4097

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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