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

This study is currently recruiting participants.
Verified January 2012 by St Stephens Aids Trust
Sponsor:
Information provided by (Responsible Party):
St Stephens Aids Trust
ClinicalTrials.gov Identifier:
NCT01475240
First received: October 31, 2011
Last updated: January 9, 2012
Last verified: January 2012
History of Changes
  Purpose

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
HIV

Study Type: Observational
Study Design: 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

Resource links provided by NLM:

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

Further study details as provided by St Stephens Aids Trust:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 100
Study Start Date: January 2012
Estimated Study Completion Date: January 2013
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
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)

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01475240

Contacts
Contact: Graeme Moyle, Dr 020 3315 6149 gm@moyleg@demon.co.uk
Contact: Carl Fletcher, Mr 020 3315 6323 carl.fletcher@chelwest.nhs.uk

Locations
United Kingdom
St Stephen's AIDS Trust Recruiting
London, United Kingdom, SW10 9NH
Contact: Carl Fletcher, Mr     020 3315 6563     carl.fletcher@chelwest.nhs.uk    
Contact: Chris Higgs, Mr     020 3315 6149     chris.higgs@chelwest.nhs.uk    
Principal Investigator: Graeme Moyle, Dr            
Sponsors and Collaborators
St Stephens Aids Trust
Investigators
Principal Investigator: Graeme Moyle, Dr St Stephen's AIDS Trust
  More Information

No publications provided

Responsible Party: St Stephens Aids Trust
ClinicalTrials.gov Identifier: NCT01475240     History of Changes
Other Study ID Numbers: SSAT 044
Study First Received: October 31, 2011
Last Updated: January 9, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by St Stephens Aids Trust:
HIV

Additional relevant MeSH terms:
Cardiovascular Diseases
Hyperbilirubinemia
Pathologic Processes
Protease Inhibitors
 Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on March 10, 2013