Clinical Trials

MainTitle

Pilot Study of Pyridostigmine Upon Immune Activation in HIV-1 Patients Who Have an Inadequate Immune Response

This study has been completed
Sponsor
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran


Information provided by (Responsible Party)
Sergio I. Valdés-Ferrer, MD, PhD, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

ClinicalTrials.gov Identifier
NCT00518154

First received: August 17, 2007
Last updated: October 24, 2019
Last Verified: October 2019
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
HIV Infections

Drug : Pyridostigmine tablets
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
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.

Further study details as provided by Sergio I. Valdés-Ferrer, MD, PhD, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran:

Primary Outcome Measures

  • CD4+ Cell Count Change Between Basal and Week 16 of Additive Treatment [ Time Frame: 16 weeks after initiation of pyridostigmine ]
    Change in total CD4+ T-cell number from baseline to addition of pyridostigmine

Enrollment: 7
Study Start Date: September 2007
Study Completion Date: January 2009
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: A
Patients will be taking oral Pyridostigmine 30mg tid, as well as their usual antiretroviral treatment
Drug: Pyridostigmine tablets

Patients will take 30mg tid PO for 12 weeks

Other Name: Mestinon

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.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

  • HIV-1 infected subjects 18 years of age or older
  • Receiving HAART for at least two years
  • At least a viral load determination per year since HAART initiation, all undetectable
  • Patient's status is Immunological Non Responder (InR), that is, his or her viral load is reduced, but CD4+ cell count has not raised accordingly
  • Current viral load: undetectable
  • Patient agrees and signs informed consent


Exclusion Criteria:
  • Concomitant active infectious or neoplastic disease
  • History of new AIDS-defining events during HAART
  • Pregnancy or breast-feeding
  • Patients who have been subjects of an investigational agent, chemotherapy or radiotherapy within the previous 28 days
  • Subjects requiring treatment for Tuberculosis
  • Subjects unable to follow, or comply with the protocol interventions
  • Subjects receiving immunosuppressive treatment, including corticosteroids

contacts and locations

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: NCT00518154

Locations

Mexico
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Tlalpan, Ciudad De México, Mexico, 14080
Sergio I. Valdés-Ferrer
Mexico City, DF, Mexico, 14080

Sponsors and Collaborators

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Investigators

Study Chair: Juan Sierra-Madero, MD Dept. of Infectious Diseases, INNSZ
Study Director: Jorge Alcocer-Varela, MD Dept. of Immunology, INNSZ
Principal Investigator: Sergio I Valdés-Ferrer, MD, PhD Dept. of Neurology, INNSZ
More Information

More Information

Additional Information:

Institute's web page

Responsible Party: Sergio I. Valdés-Ferrer, MD, PhD, Investigator, Depatment of Infectious Diseases, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran  
ClinicalTrials.gov Identifier: NCT00518154   History of Changes  
Other Study ID Numbers: Ref. 1663  
Study First Received: August 17, 2007  
Last Updated: October 24, 2019  

Keywords provided by Sergio I. Valdés-Ferrer, MD, PhD, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran:

AIDS
Immunological non-responders
Neuroimmune modulation
Pyridostigmine
Treatment Experienced

Additional relevant MeSH terms:
HIV Infections
Pyridostigmine Bromide

ClinicalTrials.gov processed this data on December 13, 2019
This information is provided by ClinicalTrials.gov.