Advertisement

Topics

A Pilot Study of the Effect of Minocycline on Cerebrospinal Fluid HIV-1 Infection

2014-08-27 03:16:03 | BioPortfolio

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.

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.

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Conditions

HIV Infection

Intervention

Minocycline

Status

Completed

Source

University of California, San Francisco

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:16:03-0400

Clinical Trials [403 Associated Clinical Trials listed on BioPortfolio]

Trial of Minocycline to Treat Children With Fragile X Syndrome

This is a single center study at the UC Davis MIND Institute in patients age 3.5-16 years of age with fragile X syndrome (FXS), funded by a National Fragile X Foundation Grant. It is a con...

Study 3: Minocycline Decreases Microglia Activation

This study is a mechanistic study that will enroll 9 subjects who are participating in NCT02133885 (which is designed to evaluate minocycline to test the hypothesis that minocycline treatm...

Safety and Efficacy Study of Copaxone Administered in Combination With Minocycline

This study investigates the add-on effect of oral minocycline in subjects treated with daily injection of Copaxone. Copaxone and minocycline are thought to have differential modes of actio...

Pilot Study of Minocycline in Huntington's Disease

This study is being conducted to assess the impact of minocycline on the progression of symptoms of HD. The study will also assess whether it is reasonable to continue with further study o...

Minocycline for the Treatment of Decreased Mental Function in HIV-Infected Adults

The purpose of this study is to determine the effectiveness of minocycline, an antibiotic, in lessening the decreased mental function sometimes caused by anti-HIV drugs.

PubMed Articles [6213 Associated PubMed Articles listed on BioPortfolio]

Minocycline suppresses dengue virus replication by down-regulation of macrophage migration inhibitory factor-induced autophagy.

Dengue virus (DENV) infection is the most prevalent mosquito-borne viral infection of which there is no licensed therapeutic drug available. Previous studies have shown that minocycline, an antibiotic...

Minocycline susceptibility breakpoints for Acinetobacter baumannii: do we need to re-evaluate them?

Minocycline is an old broad-spectrum tetracycline indicated for the treatment of various infections, including those due to minocycline-susceptible Acinetobacter spp. Susceptibility data worldwide are...

Minocycline inhibits formalin-induced inflammatory pain and the underlying mechanism.

To unravel the underlying mechanism of minocycline in formalin-induced inflammatory pain, and to investigate the effects of minocycline on synaptic transmission in substantia gela-tinosa (SG) neurons ...

Minocycline decreases Th2 chemokines from M2 macrophages: possible mechanisms for the suppression of bullous pemphigoid by traditional bullous disease drugs.

Minocycline/tetracycline is clinically used for the treatment of bullous pemphigoid (BP), and its clinical benefits are superior to those of prednisolone when considering adverse events. Although the ...

The role of minocycline in alleviating aluminum phosphide-induced cardiac hemodynamic and renal toxicity.

Poisoning with aluminum phosphide (AlP) has been attributed to the high rate of mortality among many Asian countries. It affects several organs, mainly heart and kidney. Numerous literature demonstrat...

Medical and Biotech [MESH] Definitions

A TETRACYCLINE analog, having a 7-dimethylamino and lacking the 5 methyl and hydroxyl groups, which is effective against tetracycline-resistant STAPHYLOCOCCUS infections.

Infection by a variety of fungi, usually through four possible mechanisms: superficial infection producing conjunctivitis, keratitis, or lacrimal obstruction; extension of infection from neighboring structures - skin, paranasal sinuses, nasopharynx; direct introduction during surgery or accidental penetrating trauma; or via the blood or lymphatic routes in patients with underlying mycoses.

A nontuberculous infection when occurring in humans. It is characterized by pulmonary disease, lymphadenitis in children, and systemic disease in AIDS patients. Mycobacterium avium-intracellulare infection of birds and swine results in tuberculosis.

Infection involving the tissues or organs in the PELVIS.

Infection in humans and animals caused by fungi in the class Zygomycetes. It includes MUCORMYCOSIS and entomophthoramycosis. The latter is a tropical infection of subcutaneous tissue or paranasal sinuses caused by fungi in the order Entomophthorales. Phycomycosis, closely related to zygomycosis, describes infection with members of Phycomycetes, an obsolete classification.

More From BioPortfolio on "A Pilot Study of the Effect of Minocycline on Cerebrospinal Fluid HIV-1 Infection"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

AIDS and HIV
AIDS; Acquired Immune Deficiency Syndrome. HIV; Human Immunodeficiency Virus HIV infection causes AIDS. HIV infection also causes the production of anti-HIV antibodies, which forms the test for HIV in patients. People who have the HIV antibodies are ...

Infectious-diseases
Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...

Neurology - Central Nervous System (CNS)
Alzheimer's Disease Anesthesia Anxiety Disorders Autism Bipolar Disorders Dementia Epilepsy Multiple Sclerosis (MS) Neurology Pain Parkinson's Disease Sleep Disorders Neurology is the branch of me...


Searches Linking to this Trial