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

NCT02018965 | Completed Phase 2

• 1 other identifier: CTN006
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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

Conditions

HIV

Keywords

HIV; Extended-release Niacin; Immune activation

Outcome Measures

Primary Outcomes (2)

• Comparison of the change in CD8CD38 percentage

  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)

  24 weeks

• Comparison of the change in CD8CD38 percentage during the ER niacin + ART period

  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

  48 weeks

Secondary Outcomes (4)

• Change in CD4 cell count and their subsets, including naïve, central memory and effector memory and Th17/Treg cells

  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 plasmatic Trp levels

  48 weeks

• Changes in total cholesterol, HDL, LDL cholesterol and triglycerides

  48 weeks

Study Arms (2)

ER niacin followed by ART alone

OTHER

For Arm 1, ER niacin administration begins Week 0 and ends Week 24 (defined as 'immediate use' arm).

Drug: Niacin

ART alone followed by ER niacin

OTHER

For Arm 2, ER niacin administration begins after the Week 24 Visit and ends Week 48 (defined as 'deferred use' arm).

Drug: Niacin

Interventions

Niacin DRUG

• Group 1: This group will receive an initial dose of ER niacin 500 mg by mouth, the first evening from week 0 to week 4 then increase it to 1000 mg once a day from week 5 to week 8, then increase to 1500 mg from week 9 to week 12 then increase to 2000 mg until weeks 24 and then stopped. Participants will continue to take their ART treatment as prescribed throughout the study.

Also known as: Niaspan FCT®, extended-release(ER)Niacin, vitamin B3

ART alone followed by ER niacin; ER niacin followed by ART alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Participants must meet all of the following criteria within four weeks prior to the Week 0 (Baseline) Visit to be considered eligible for entry into the study: 1. Documented HIV infection by Western Blot, EIA assays or viral load assay 2. Aged 21 or older 3. Viral load \< 50 copies/mL for the last 3 months 4. CD4 cell count \< 350 cells/µL 5. On stable ART, i.e., ART unchanged for treatment failure (rebound in viral load) for more than 12 months 6. Able to communicate adequately in either French or English 7. Able and willing to give written informed consent prior to enrolment including access to relevant medical records. Participants are not eligible to participate in the study if any of the following conditions are met: 1. Pregnant, breastfeeding or planning to become pregnant during the course of the study. All fecund female participants must undergo a pregnancy test, with a negative result, prior to being eligible to participate in the study 2. Prior history of hypersensitivity reaction to niacin or any other component of the study drug 3. Prior history of flushing 4. Active liver disease or unexplained persistent elevations of serum transaminases 5. Co-infection with active Hepatitis B or C virus (positive HBs Ag or positive anti HBc antibodies with a detectable HBV DNA viral load or positive anti HCV antibodies with a detectable HCV RNA viral load) 6. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or alkaline phosphatase \>2.5 x upper limit of normal (ULN) 7. Active duodenal or gastric peptic ulcer 8. Active bleeding disorders 9. History of gout 10. Active AIDS events in the last 3 months as determined by the treating physician 11. Unstable angina or acute phase myocardial infarction, with or without vasodilator agents 12. Diabetic or potentially diabetic with hypercholesterolaemia 13. Renal dysfunction.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead
• CIHR Canadian HIV Trials Network: collaborator

Study Sites (1)

Montreal Chest Institute

Montreal, Quebec, H2W1T7, Canada

Location

Related Publications (1)

• Lebouche B, Jenabian MA, Singer J, Graziani GM, Engler K, Trottier B, Thomas R, Brouillette MJ, Routy JP. The role of extended-release niacin on immune activation and neurocognition in HIV-infected patients treated with antiretroviral therapy - CTN PT006: study protocol for a randomized controlled trial. Trials. 2014 Oct 7;15:390. doi: 10.1186/1745-6215-15-390.

  PMID: 25293882 DERIVED

MeSH Terms

Interventions

Niacin; Niacinamide

Intervention Hierarchy (Ancestors)

Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Bertrand Lebouché, MD, PhD

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: December 17, 2013
• First Posted: December 24, 2013
• Study Start: November 1, 2011
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: April 23, 2018

Record last verified: 2018-04

Locations

CA (1)