Ignite Creation Date:
2024-05-05 @ 6:37 PM
Last Modification Date:
2024-10-26 @ 9:35 AM
Study NCT ID:
NCT00518154
Status:
COMPLETED
Last Update Posted:
2019-11-14
First Post:
2007-08-17
Brief Title:
Pilot Study of Pyridostigmine Upon Immune Activation in HIV-1 Patients Who Have an Inadequate Immune Response
Sponsor:
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Organization:
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Study Overview
Official Title:
Pilot Study of an ACh-E Inhibitor Upon Immune Activation Markers in HIV-1 Infected Patients Receiving Highly Active Antiretroviral Therapy HAART Showing an Incomplete Immune Response
Status:
COMPLETED
Status Verified Date:
2019-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to determine whether the addition of Pyridostigmine to Highly Active Antiretroviral Therapy HAART increases the number of CD4 T-cells in discordant patients in which viral load diminishes but T-cell levels remain low after the initiation of treatment
Detailed Description:
In HIV-1 infected patients HAART suppresses viral replication reflected by a reduced viral load and a recovery in the frequency of CD4 T-cells The latter is associated with a reduced risk for developing opportunistic infectious diseases and death T-cell recovery however is highly variable within individuals suggesting that virological eradication is but one factor of it
A phenomenon known as Immune Discordance has been well known It reflects a subpopulation -as high as 30 of patients- in whom there is an adequate suppression of viral replication but CD4 cell levels rise modestly below safety levels In this setting patients remain susceptible to develop opportunistic infections have disease progression and die Various mechanisms have been proposed but one common factor is enhanced CD4-cell activation leading to cell dysfunction and apoptosis
It is known that an inflammatory response is able to activate the anti-inflammatory cholinergic pathway in which acetylcholine ACh is released and in turn activates nicotinic receptors in macrophages The result is a diminished synthesis of inflammatory cytokines such as TNF-α and IL-1 We have recently shown in an ex-vivo proof-of-concept study carried in HIV-infected subjects in early phases of the infection not requiring specific treatment that Pyridostigmine diminishes CD4-cell activation and an increase in the subpopulation of regulatory T-cells T-reg
Pyridostigmine an ACh-esterase inhibitor has been shown to be safe in other populations including healthy Gulf War military personnel and patients with Myasthenia Gravis Its hypothetical effect is by reducing the degrading rate of the naturally occurring ACh released by the vagus nerve by the enzyme ACh-esterase This in turn enhances its coupling to nicotinic receptors in macrophages that according to our previous study unpublished data improves the T-cell milieu diminishes T-cell activation a well known trigger for apoptosis and enhances T-reg proliferation
The purpose of this study is to determine whether the addition of Pyridostigmine to Highly Active Antiretroviral Therapy HAART increases the number of CD4 T-cells in discordant patients in which viral load diminishes but T-cell levels remain low after the initiation of treatment
A phenomenon known as Immune Discordance has been well known It reflects a subpopulation -as high as 30 of patients- in whom there is an adequate suppression of viral replication but CD4 cell levels rise modestly below safety levels In this setting patients remain susceptible to develop opportunistic infections have disease progression and die Various mechanisms have been proposed but one common factor is enhanced CD4-cell activation leading to cell dysfunction and apoptosis
It is known that an inflammatory response is able to activate the anti-inflammatory cholinergic pathway in which acetylcholine ACh is released and in turn activates nicotinic receptors in macrophages The result is a diminished synthesis of inflammatory cytokines such as TNF-α and IL-1 We have recently shown in an ex-vivo proof-of-concept study carried in HIV-infected subjects in early phases of the infection not requiring specific treatment that Pyridostigmine diminishes CD4-cell activation and an increase in the subpopulation of regulatory T-cells T-reg
Pyridostigmine an ACh-esterase inhibitor has been shown to be safe in other populations including healthy Gulf War military personnel and patients with Myasthenia Gravis Its hypothetical effect is by reducing the degrading rate of the naturally occurring ACh released by the vagus nerve by the enzyme ACh-esterase This in turn enhances its coupling to nicotinic receptors in macrophages that according to our previous study unpublished data improves the T-cell milieu diminishes T-cell activation a well known trigger for apoptosis and enhances T-reg proliferation
The purpose of this study is to determine whether the addition of Pyridostigmine to Highly Active Antiretroviral Therapy HAART increases the number of CD4 T-cells in discordant patients in which viral load diminishes but T-cell levels remain low after the initiation of treatment
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None