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

April 10, 2014 updated by: St Stephens Aids Trust

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
101

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, SW10 9NH
        • St Stephen's AIDS Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

HIV-infected males/females aged 18 years and above

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
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)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
1 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
St Stephens Aids Trust

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Graeme Moyle, Dr, St Stephen's AIDS Trust

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 31, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 16, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 21, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 11, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 10, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SSAT 044

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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