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

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

Patrocinadores

Patrocinador principal: South East Asia Research Collaboration with Hawaii

Colaborador: University of Hawaii

Fuente South East Asia Research Collaboration with Hawaii
Resumen breve

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.

Descripción detallada

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.

Estado general Completed
Fecha de inicio May 2010
Fecha de Terminación December 2012
Fecha de finalización primaria November 2012
Tipo de estudio Observational
Resultado primario
Medida Periodo de tiempo
Number of nerves in the skin Baseline
Condition of lipoatrophy Baseline
Resultado secundario
Medida Periodo de tiempo
Mitochondrial parameters Baseline
Intracellular concentrations of d4T triphosphate Baseline
HIV DNA in peripheral blood mononuclear cell (PBMC) Baseline
Inscripción 113
Condición
Elegibilidad

Método de muestreo: Non-Probability Sample

Criterios:

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.

Género: All

Edad mínima: 18 Years

Edad máxima: N/A

Voluntarios Saludables: No

Oficial general
Apellido Papel Afiliación
Jintanat Ananworanich, MD, PhD Principal Investigator South East Asia Research Collaboration with Hawaii
Ubicación
Instalaciones: Thai Red Cross AIDS Research Centre
Ubicacion Paises

Thailand

Fecha de verificación

September 2014

Fiesta responsable

Tipo: Principal Investigator

Afiliación del investigador: South East Asia Research Collaboration with Hawaii

Nombre completo del investigador: Assoc.Prof.Jintanat Ananworanich, M.D.

Título del investigador: Assoc.Prof. Jintanat Ananworanich, MD,PhD

Palabras clave
Tiene acceso ampliado No
Grupo de brazo

Etiqueta: 1: HIV-pos on d4T with neuropathy

Etiqueta: 2: HIV-pos on d4T without neuropathy

Etiqueta: 3: HIV-neg without peripheral neuropathy

Etiqueta: 4 HIV-pos on d4T with asymtomatic neuropathy

Información de diseño del estudio

Modelo de observación: Case-Crossover

Perspectiva de tiempo: Cross-Sectional

Fuente: ClinicalTrials.gov