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

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ClinicalTrials.gov Identifier: NCT01475240
Recruitment Status : Completed
First Posted : November 21, 2011
Last Update Posted : April 11, 2014
Sponsor:
Information provided by (Responsible Party):
St Stephens Aids Trust

Study Description
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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:

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.


Condition or disease
HIV

Detailed Description:

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


Study Design
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Study Type : Observational
Actual Enrollment : 101 participants
Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: 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
Study Start Date : January 2012
Actual Primary Completion Date : November 2013
Actual Study Completion Date : November 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS Jaundice
U.S. FDA Resources

Groups and Cohorts
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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort
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)


Outcome Measures
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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. To evaluate the impact of hyperbilirubinemia on markers of cardiovascular disease [ Time Frame: 1 year ]
    Assessment of Pulse Wave Velocity; Carotid intimal thickness; Vascular markers (iCAM, vCAM); Lipid fractions and sub fractions


Secondary Outcome Measures :
  1. To evaluate the impact of hyperbilirubinemia on neurocognitive function and renal markers [ Time Frame: 1 year ]
    Assment of Neurocognitive testing; IL-6, d-dimer, uric acid, and hs-CRP; Urinary protein / creatinine ratio; Urinary Retinal binding / protein ratio


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
HIV-infected males/females aged 18 years and above
Criteria

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.
Contacts and Locations
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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01475240


Locations
United Kingdom
St Stephen's AIDS Trust
London, United Kingdom, SW10 9NH
Sponsors and Collaborators
St Stephens Aids Trust
Investigators
Principal Investigator: Graeme Moyle, Dr St Stephen's AIDS Trust
More Information
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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party: St Stephens Aids Trust
ClinicalTrials.gov Identifier: NCT01475240     History of Changes
Other Study ID Numbers: SSAT 044
First Posted: November 21, 2011    Key Record Dates
Last Update Posted: April 11, 2014
Last Verified: April 2014

Keywords provided by St Stephens Aids Trust:
HIV

Additional relevant MeSH terms:
Hyperbilirubinemia
Pathologic Processes