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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2010 by South East Asia Research Collaboration with Hawaii.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
University of Hawaii
Information provided by:
South East Asia Research Collaboration with Hawaii
ClinicalTrials.gov Identifier:
NCT01178684
First received: June 11, 2010
Last updated: July 21, 2011
Last verified: May 2010
  Purpose

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.


Condition
HIV

Study Type: Observational
Study Design: Observational Model: Case-Crossover
Time Perspective: Cross-Sectional
Official Title: 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

Resource links provided by NLM:


Further study details as provided by South East Asia Research Collaboration with Hawaii:

Primary Outcome Measures:
  • Number of nerves in the skin [ Time Frame: Baseline ] [ Designated as safety issue: No ]

    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

  • Condition of lipoatrophy [ Time Frame: Baseline ] [ Designated as safety issue: No ]

    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


Secondary Outcome Measures:
  • Mitochondrial parameters [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Intracellular concentrations of d4T triphosphate [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • HIV DNA in peripheral blood mononuclear cell (PBMC) [ Time Frame: Baseline ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

Plasma PBMC Urine CBC


Estimated Enrollment: 98
Study Start Date: May 2010
Estimated Study Completion Date: August 2012
Estimated Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01178684

Contacts
Contact: Jintanat Ananworanich, MD,PhD 6622542566 jintanat.a@searchthailand.org

Locations
Thailand
Thai Red Cross AIDS Research Centre Recruiting
Bangkok, Thailand
Contact: Nitiya Chomchey, M.Sc.    6622542566 ext 110    nitiya.c@searchthailand.org   
Sponsors and Collaborators
South East Asia Research Collaboration with Hawaii
University of Hawaii
Investigators
Principal Investigator: Jintanat Ananworanich, MD, PhD South East Asia Research Collaboration with Hawaii
  More Information

No publications provided

Responsible Party: Jintanat Ananworanich, South East Asia Collaboration with Hawaii
ClinicalTrials.gov Identifier: NCT01178684     History of Changes
Other Study ID Numbers: SEARCH 014
Study First Received: June 11, 2010
Last Updated: July 21, 2011
Health Authority: Thailand: Ethical Committee

Keywords provided by South East Asia Research Collaboration with Hawaii:
ENFD
epidermal nerve fiber density
HIV
HIV-infection

ClinicalTrials.gov processed this record on July 09, 2014