A Pilot Study of the Effect of Minocycline on Cerebrospinal Fluid HIV-1 Infection
Information source: University of California, San Francisco
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infection
Intervention: Minocycline (Drug)
Phase: N/A
Status: Completed
Sponsored by: University of California, San Francisco Official(s) and/or principal investigator(s): Richard W Price, MD, Principal Investigator, Affiliation: University of California, San Francisco
Summary
This will be an uncontrolled, open-labelled pilot study exploring whether minocycline has a
measurable and selective effect on HIV infection of the central nervous system.
Clinical Details
Official title: A Pilot Study of the Effect of Minocycline on Cerebrospinal Fluid HIV-1 Infection
Study design: Observational Model: Case-Only, Time Perspective: Prospective
Detailed description:
This study is founded on a sequence of related hypotheses: 1. inflammatory responses related
to activation of macrophages importantly contribute to the magnitude of CNS HIV infection by
increasing the local production of viral progeny; 2. the tetracycline, minocycline, has
anti-inflammatory properties which likely underlie studies showing that this drug can
inhibit HIV-1 infection in macrophages and microglia in vitro and reduce simian
immunodeficiency virus (SIV) encephalitis in macaques; 3. by reducing CNS
monocyte/macrophage/microglial activation, minocycline will therefore reduce CNS HIV
infection; 4. CSF will reflect or parallel (and thus serve as a 'model' of) brain infection
and inflammation in this setting; 5. therefore, longitudinal CSF monitoring can assess the
effect of minocycline on both CNS HIV infection and inflammation; 6. because the brain
injury underlying AIDS dementia complex (ADC) and its pathological substrate, HIV
encephalitis, critically involve inflammatory processes and, in the broad sense,
immunopathology, minocycline might eventually prove useful as an adjunct to antiviral
therapy in accelerating recovery from this condition (though importantly, this pilot study
will not include ADC patients).
This will be an uncontrolled, open-labelled pilot study exploring whether minocycline has a
measurable and selective effect on CSF HIV RNA concentration. There are no previous studies
examining this effect in humans. We define a priori a 'biologically meaningful' effect to be
an increase in the Δplasma-CSF HIV concentration of >0. 5 log10 copies/mL of HIV RNA (i. e. an
increase in the difference between plasma and CSF of >0. 5 log10 copies/mL of HIV RNA
compared to the baseline difference) in the face of unchanged or reduced plasma HIV RNA.
Reductions in the absolute levels of CSF and plasma HIV as well as reductions in CSF
inflammatory markers and T cell activation will also be of interest.
This study will serve as an initial exploration of the possible therapeutic effect of
minocycline on CNS HIV infection. Our overall strategy is to begin with this pilot study,
and if the results look promising (biological effect and lack of toxicity), to use these
results to design a controlled trial, either as a single or multi-institutional study.
Additionally, this study shares an almost identical design with another proposed study
examining the effects of atorvastatin on CSF HIV infection. While neither of these studies
is controlled, they will yield pilot comparative results.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. HIV infection with plasma and CSF HIV RNA concentrations (using Roche Amplicor assay)
> 1,000 copies/ mL (available after baseline LP).
2. Off antiretroviral therapy (ART) for > 6 weeks before the study and no plans to begin
treatment for the study duration. (The decision of whether or not a subject takes
antiretroviral therapy will be made by the subject in consultation with his/her
primary care provider prior to screening for this study.)
3. Predicted adherence to the medication.
4. Capable of providing informed consent.
5. > 18 years old
6. CD4 cell counts >150 cells/μL (though likely most, if not all, will be >250
cells/μL).
7. When available, subjects will be screened for stability of blood CD4 and HIV RNA
levels.
Exclusion Criteria:
1. Taking a tetracycline within 6 months or history of adverse reaction to minocycline
or another tetracycline.
2. Enhanced risk from lumbar puncture, including documented or suspected cerebral mass
lesion predisposing to brain herniation or bleeding diathesis.
3. Pregnancy or expectation of pregnancy during the study.
4. Active opportunistic infection or active neurological disease that might confound
evaluation.
5. ADC Stage > 1.
6. Hemoglobin < 10 Gms/dL.
7. BUN or creatine above the normal limits.
8. Taking other drugs known to reduce the metabolism of minocycline and thus increase
the probability of toxicity.
Locations and Contacts
Additional Information
Starting date: April 2005
Last updated: February 5, 2010
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