Niacin on Immune Activation : a Proof-of-concept Study
Nøgleord
Abstrakt
Beskrivelse
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
Datoer
| Sidst bekræftet: | 03/31/2018 |
| Først indsendt: | 12/16/2013 |
| Anslået tilmelding indsendt: | 12/16/2013 |
| Først indsendt: | 12/23/2013 |
| Sidste opdatering indsendt: | 04/18/2018 |
| Sidste opdatering indsendt: | 04/22/2018 |
| Faktisk startdato for undersøgelsen: | 10/31/2011 |
| Anslået primær afslutningsdato: | 05/31/2017 |
| Anslået afslutningsdato for undersøgelsen: | 05/31/2017 |
Tilstand eller sygdom
Intervention / behandling
Drug: Niacin
Drug: Niacin
Fase
Armgrupper
| Arm | Intervention / behandling |
|---|---|
| Other: ER niacin followed by ART alone For Arm 1, ER niacin administration begins Week 0 and ends Week 24 (defined as 'immediate use' arm). | |
| Other: ART alone followed by ER niacin For Arm 2, ER niacin administration begins after the Week 24 Visit and ends Week 48 (defined as 'deferred use' arm). |
Kriterier for støtteberettigelse
| Alder berettiget til undersøgelse | 18 Years Til 18 Years |
| Køn, der er berettiget til undersøgelse | All |
| Accepterer sunde frivillige | Ja |
| Kriterier | 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. |
Resultat
Primære resultatforanstaltninger
1. Comparison of the change in CD8CD38 percentage [24 weeks]
2. Comparison of the change in CD8CD38 percentage during the ER niacin + ART period [48 weeks]
Sekundære resultatforanstaltninger
1. Change in CD4 cell count and their subsets, including naïve, central memory and effector memory and Th17/Treg cells [48 weeks]
2. Changes in inflammatory markers such as INF-α, IL-1, IL-6, IL-17, usCRP, LPS and D-dimers [48 weeks]
3. Change in plasmatic Trp levels [48 weeks]
4. Changes in total cholesterol, HDL, LDL cholesterol and triglycerides [48 weeks]
