Niacin on Immune Activation : a Proof-of-concept Study

Phase 2

Completed

• Conditions: HIV
• Interventions: Drug: Niacin

• Registration Number: NCT02018965
• Lead Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Brief Summary

There are a number of powerful anti-HIV drugs, which keep the virus at undetectable levels and enable HIV-infected individuals to live longer. However, some participants taking anti-HIV drugs do not achieve an adequate CD4 recovery and remain at risk for developing AIDS and non-AIDS-related complications.

ER niacin (PrNiaspanFCT®) is an extended-released form of niacin, also known as vitamin B3. Niacin is effective in reducing cholesterol levels in the blood. This drug has been known for a long-time to treat dyslipidemia and it is used to improve favourably all the lipoprotein risk factors for artherosclerotic disease, particularly in HIV-infected patients. Recent scientific research shows that regular consumption of niacin-rich foods may also provide protection against Alzheimer's disease and age-related cognitive decline.

The purpose of this study is to find out:

1. If ER niacin combined with anti-HIV drugs, compared with anti-HIV drugs alone, could reduce T cell immune activation and enhance CD4 recovery;

2. If ER niacin can improve your quality of life and your neurocognitive functions

Detailed Description

Primary objective

• To assess the impact of extended-release niacin (ER niacin) supplementation + antiretroviral therapy (ART) compared to ART alone on T-cell immune activation as defined by CD8CD38 percentage

Secondary objectives

* To assess the change in total CD4 T-cell count after ER niacin administration

* To explore the effect of ER niacin on regulatory T-cells (Th-17/Treg) in blood and gut mucosa samples

* To explore the effect of ER niacin on cytokines and inflammatory markers such as INF-α, IL-1, IL-6, IL-17, D-dimers, usCRP and LPS

* To assess the influence of ER niacin on tryptophan (Trp) plasmatic levels

* To assess changes in cholesterol and triglycerides

* To explore ER niacin tolerance

* To evaluate the impact of ER niacin on quality of life (QoL), fatigue, depression, and neurocognitive scores

Population: All participants will have an undetectable HIV viral load (\< 50 copies/mL) for at least 3 months, current CD4 cell count of \< 350 cells/µL and be receiving ART for at least the previous 12 months.

Sample size: N=20

Study Timeline

• Study Start: 2011-11
• Study First Submitted: 2013-12-17
• Study First Submitted QC: 2013-12-17
• Study First Posted: 2013-12-24
• Primary Completion: 2017-06
• Study Completion: 2017-06
• Status Verified: 2018-04
• Last Update Submitted: 2018-04-19
• Last Update Posted: 2018-04-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
ER niacin followed by ART alone	Niacin	For Arm 1, ER niacin administration begins Week 0 and ends Week 24 (defined as 'immediate use' arm).
ART alone followed by ER niacin	Niacin	For Arm 2, ER niacin administration begins after the Week 24 Visit and ends Week 48 (defined as 'deferred use' arm).

Primary Outcome Measures

Name	Time	Method
Comparison of the change in CD8CD38 percentage during the ER niacin + ART period	48 weeks	Comparison of the change in CD8CD38 percentage during the ER niacin + ART period with the change in CD8CD38 during the ART alone period within each arm (Week 0 to Week 24 vs. Week 24 to Week 48 for Arm 1 and Week 24 to Week 48 vs. Week 0 to Week 24 for Arm 2); if the difference between ER niacin versus control is similar in the two time periods, the treatment effect will be pooled adjusting for treatment order
Comparison of the change in CD8CD38 percentage	24 weeks	Comparison of the change in CD8CD38 percentage from Week 0 to Week 24 of Arm 1 (ER niacin + ART) to Week 0 to Week 24 of Arm 2 (ART alone) (ER niacin treatment + ART vs. ART alone for 24 weeks)

Secondary Outcome Measures

Name	Time	Method
Change in plasmatic Trp levels	48 weeks
Changes in total cholesterol, HDL, LDL cholesterol and triglycerides	48 weeks
Changes in inflammatory markers such as INF-α, IL-1, IL-6, IL-17, usCRP, LPS and D-dimers	48 weeks
Change in CD4 cell count and their subsets, including naïve, central memory and effector memory and Th17/Treg cells	48 weeks

Trial Locations

Locations (1)

Montreal Chest Institute; 🇨🇦 Montreal, Quebec, Canada