The Effect of Hyperbilirubinemia on CV Disease, Neurocog Function and Renal Function (SSAT044)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
St Stephens Aids Trust
ClinicalTrials.gov Identifier:
NCT01475240
First received: October 31, 2011
Last updated: April 10, 2014
Last verified: April 2014

October 31, 2011
April 10, 2014
January 2012
November 2013   (final data collection date for primary outcome measure)
To evaluate the impact of hyperbilirubinemia on markers of cardiovascular disease [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Assessment of Pulse Wave Velocity; Carotid intimal thickness; Vascular markers (iCAM, vCAM); Lipid fractions and sub fractions
Same as current
Complete list of historical versions of study NCT01475240 on ClinicalTrials.gov Archive Site
To evaluate the impact of hyperbilirubinemia on neurocognitive function and renal markers [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Assment of Neurocognitive testing; IL-6, d-dimer, uric acid, and hs-CRP; Urinary protein / creatinine ratio; Urinary Retinal binding / protein ratio
Same as current
Not Provided
Not Provided
 
The Effect of Hyperbilirubinemia on CV Disease, Neurocog Function and Renal Function
A Cross-sectional Controlled Study to Evaluate the Impact of Hyperbilirubinemia on Markers of Cardiovascular Disease, Neurocognitive Function and Renal Markers in HIV-1 Infected Subjects on Protease Inhibitors

Use of some protease inhibitors is associated with elevations of a blood pigment called bilirubin. This may occasionally lead to yellowing of the eyes (scleral icterus) or jaundice, but in the general population bilirubin elevations have been shown to have antioxidant and anti-inflammatory properties that could be associated with reduced risk of cardiovascular or other disease events.

Inflammation may also be relevant to neurocognitive impairment in HIV (Human Immunodeficiency Virus) infection hence elevations of bilirubin may also be protective against neurocognitive impairment.

The purpose of this study is to evaluate the impact of hyperbilirubinemia (HBR) on risk of heart and renal diseases, and cognitive function.

Use of some protease inhibitors is associated with unconjugated hyperbilirubinemia as a result of inhibition of the UGT1A1 enzyme.

Elevated levels of unconjugated bilirubin are best characterized among individuals with Gilbert syndrome, which is the most common inherited cause of unconjugated hyperbilirubinemia, present in 3-10% of the general population. Gilbert syndrome arises through variants in the UGT1A1 enzyme, thus these PIs induce a biochemical picture similar to Gilbert syndrome. Although elevations of bilirubin may occasionally lead to scleral icterus or jaundice, cohort studies of individuals with Gilbert syndrome indicate bilirubin elevations may have antioxidant and anti-inflammatory properties and are associated with reduced risk of cardiovascular events.

Inflammation may also be relevant to cardiovascular (CV) risk, neurocognitive impairment and renal disease in HIV infection. This study seeks to investigate any association between antiretroviral associated HBR and CV risk markers, neurocognitive impairment and renal dysfunction

Observational
Observational Model: Case Control
Time Perspective: Cross-Sectional
Not Provided
Not Provided
Probability Sample

HIV-infected males/females aged 18 years and above

HIV
Not Provided
  • Group 1: Controls
    HIV-infected patients on stable > 6 months on TDF/FTC or ABC/3TC plus PI/r based ARV regimen with normal bilirubin
  • Group 2: Cases
    HIV-infected patients on stable >6 months on TDF/FTC or ABC/3TC plus PI/r based ARV regimen with HBR (>2.5 X upper limit)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
101
November 2013
November 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. The ability to understand and sign a written informed consent form, prior to participation in any screening procedure and must be willing to comply with all study requirements.
  2. Documented HIV-1 infection.
  3. >18 years of age
  4. Stable on PI based therapy with TDF/FTC or ABC/3TC > 6 months with either normal bilirubin or bilirubin >2.5 X upper limit
  5. Stable for > 3 months on lipid lowering therapy, anticoagulant, hormone supplements, metformin (for lipohypertrophy) or other metabolic therapies
  6. No known or past history of cardiovascular disease, neurocognitive disorder or renal disease.

Exclusion Criteria:

  1. Grade 1-2 Bilirubin
  2. Known CV disease (angina, coronary artery disease, peripheral vascular disease, stroke, congestive cardiac failure or myocardial dysfunction), Diabetes Mellitus, antihypertensive therapy
  3. Chronic NSAID use including low dose aspirin
  4. Known renal or CNS or neurocognitive disease
  5. HIV RNA >400copies/ml in last 6 months
  6. Change of antiretroviral Therapy in last 6 months
  7. Active Hepatitis B (sAg +ve) or hepatitis C (detectable HCV RNA,, treated or cleared Hepatitis C permitted if infection and/or treatment > 6months previous)
  8. Use of anabolic steroids. Cutaneous administered testosterone supplements stable for >3 months for documented hypogonadism permitted. Oral contraceptives stable for 3 months permitted.
Both
18 Years and older
Yes
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
NCT01475240
SSAT 044
No
St Stephens Aids Trust
St Stephens Aids Trust
Not Provided
Principal Investigator: Graeme Moyle, Dr St Stephen's AIDS Trust
St Stephens Aids Trust
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP