Epidermal Nerve Fiber Density, Fat and Mitochondrial Parameters in Thai HIV+ Patients on d4T and HIV- Patients

September 25, 2014 updated by: Assoc.Prof.Jintanat Ananworanich, M.D., South East Asia Research Collaboration with Hawaii

Study of Epidermal Nerve Fiber Density, Subcutaneous Fat, and Mitochondrial Parameters in Thai HIV-positive Patients on Long-term Stavudine Treatment and in Thai HIV-negative Patients

This study will provide the range of Epidermal Nerve Fiber Density (ENFD) typically seen in Thai individuals. ENFD values from Thai HIV-negative subjects without neuropathy will be used as appropriate reference norm for Thai HIV-positive subjects. In particular, comparison of ENFD values from Thai HIV-negative subjects with baseline ENFD values in Thai HIV-positive subjects prior to highly active antiretroviral therapy (HAART) will allow examination of the effect of HIV per se on ENFD. ENFD from Thai HIV-positive subjects on long-term d4T (stavudine) with and without neuropathy will also provide reference ENFD values at the extremes of the disease process i.e. extent of ENFD decrease in subjects with d4T-induced symptomatic neuropathy and in subjects completely free of disease despite d4T treatment for comparison with Thai HIV-positive subjects on short-term d4T in SEARCH 003 study.

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

The range of changes in epidermal nerve fiber density (ENFD), subcutaneous fat, and mitochondrial function induced by stavudine (d4T)-based therapy is currently not known, globally or specifically in the Thai population. This study will evaluate ENFD and subcutaneous fat and peripheral blood mitochondrial parameters in 4 groups of subjects. Group 1 will include Thai HIV-positive subjects on long-term d4T treatment with symptomatic peripheral neuropathy. Group 2 will include Thai HIV-positive subjects on long-term d4T treatment without peripheral neuropathy. Group 3 will include HIV-negative subjects without peripheral neuropathy.Group 4 will include Thai HIV-positive subjects on long-term d4T treatment with asymptomatic peripheral neuropathy. Information gained from Thai HIV-positive subjects on long-term d4T treatment with and without neuropathy in this study will provide range of positive control values for subjects in the SEARCH 003 study and other studies looking at the influence of antiretroviral agents on peripheral nerve, fat, and mitochondria. Information gained from Thai HIV-negative subjects without neuropathy can be used as negative control values for subjects in the SEARCH 003 study and other studies looking at the influence of HIV or other diseases/pathogens on peripheral nerve, fat, and mitochondria.

Hypothesis

  1. HIV-positive patients who have been on long-term d4T treatment with symptomatic peripheral neuropathy will have less ENFD, increased lipoatrophy, and altered mitochondrial function than those on long-term d4T treatment with asymptomatic peripheral neuropathy and those on long-term d4T treatment without peripheral neuropathy.
  2. HIV-negative patients without peripheral neuropathy will have more ENFD, no lipoatrophy, and better mitochondrial function than HIV-positive patients.

The SEARCH 003 study will assess the extent of deterioration in ENFD induced by short-term (from entry to 24 weeks) d4T use and the degree of improvement following discontinuation of d4T (from week 24 to 72). However the range of changes in ENFD and in other mitochondrial parameters induced by d4T-based therapy in not known, globally or specifically in the Thai population.

This is a cross-sectional study that will enroll 25 HIV-positive subjects on long-term d4T treatment with symptomatic peripheral neuropathy, 25 HIV-positive subjects on long-term d4T treatment without peripheral neuropathy, 50 HIV-negative subjects without peripheral neuropathy and 25 HIV-positive subjects on long-term d4T treatment with asymptomatic peripheral neuropathy for a one-time assessment.

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.
113

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

  • Thailand
      • Bangkok, Thailand
        • Thai Red Cross Aids Research Centre

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

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Seventy five HIV-positive patients on long-term d4T treatment (25 with symptomatic peripheral neuropathy, 25 without peripheral neuropathy and 25 with asymptomatic peripheral neuropathy) and 50 HIV-negative subjects without peripheral neuropathy will be recruited from the Thai Red Cross AIDS Research Centre and the Queen Savang Vadhana Memorial Hospital.

Description

Group 1: HIV-positive subjects on long-term d4T with symptomatic peripheral neuropathy

Inclusion Criteria:

  • Documented HIV-1 infection
  • Age ≥ 18 years old
  • Has Thai national identification card
  • Subject on d4T treatment with symptoms of neuropathy which developed after start of d4T therapy
  • Evidence of symptomatic persistent symptoms of pain, tingling or numbness of lower extremities AND bilateral lower extremity neuropathy on exam at entry.
  • Subject understands the study and is able to sign informed consent
  • HIV RNA by PCR < 50 copies/mL

Exclusion Criteria:

  • Treatment with concomitant medications (other than d4T) or having conditions (e.g. compressive neuropathy, diabetes, vitamin B12 deficiency, excessive alcohol intake meeting substance dependence criteria by DSM-IV, hepatitis C infection) known to cause neuropathy
  • History of allergy to any anesthetic medications
  • Pregnancy

Group 2 subjects will meet the same criteria described above for group 1 subjects, but will NOT have symptoms OR signs of neuropathy.

Group 3 subjects will meet the same criteria described above for group 1 subjects, but will NOT have symptoms OR signs of neuropathy and will have documented

Group 4 subjects will meet the same criteria described above for group 1 subject, but will have evidence of symptomatic persistent symptoms of pain, tingling or numbness of lower extremities.

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.
1: HIV-pos on d4T with neuropathy
2: HIV-pos on d4T without neuropathy
3: HIV-neg without peripheral neuropathy
4 HIV-pos on d4T with asymtomatic neuropathy

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
Number of nerves in the skin
Time Frame: Baseline

To compare differences in ENFD between the 4 groups

  • group 1: HIV-positive subjects on long-term d4T with symptomatic peripheral neuropathy
  • group 2: HIV-positive subjects on long-term d4T without peripheral neuropathy
  • group 3: HIV-negative subjects without peripheral neuropathy
  • group 4: HIV-positive subjects on long-term d4T with asymptomatic peripheral neuropathy
Baseline
Condition of lipoatrophy
Time Frame: Baseline

To compare differences lipoatrophy between the 4 groups

  • group 1: HIV-positive subjects on long-term d4T with symptomatic peripheral neuropathy
  • group 2: HIV-positive subjects on long-term d4T without peripheral neuropathy
  • group 3: HIV-negative subjects without peripheral neuropathy
  • group 4: HIV-positive subjects on long-term d4T with asymptomatic peripheral neuropathy
Baseline

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
Time Frame
Mitochondrial parameters
Time Frame: Baseline
Baseline
Intracellular concentrations of d4T triphosphate
Time Frame: Baseline
Baseline
HIV DNA in peripheral blood mononuclear cell (PBMC)
Time Frame: Baseline
Baseline

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.
South East Asia Research Collaboration with Hawaii

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Hawaii

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: Jintanat Ananworanich, MD, PhD, South East Asia Research Collaboration with Hawaii

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.
May 1, 2010

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, 2012

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.
December 1, 2012

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).
June 11, 2010

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.
August 9, 2010

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.
August 10, 2010

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.
September 26, 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.
September 25, 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.
September 1, 2014

More Information

Terms related to this study

Keywords

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.
  • SEARCH 014

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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