HIV InfectionsPhase 2NCT00518154
Pilot Study of Pyridostigmine Upon Immune Activation in HIV-1 Patients Who Have an Inadequate Immune Response
A Phase 2 study testing Pyridostigmine tablets in people with HIV Infections, run by Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran at 2 sites in Mexico.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Pyridostigmine tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 2 sitesMexico
- Study dates
- Sep 2007to Jan 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
Mexico2 sites
Sergio I. Valdés-Ferrer
Mexico City, Mexico City, 14080
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Tlalpan, Mexico City, 14080
About this study
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.
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.
Read the 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.
- Conditions
- HIV Infections
- Being tested
- Pyridostigmine tablets
- Keywords
- AIDS, Immunological non-responders, Neuroimmune modulation, Pyridostigmine, Treatment Experienced
- Medical subject headings
- HIV Infections, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pyridostigmine tabletsDrug
Also called Mestinon
Patients will take 30mg tid PO for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Patients will be taking oral Pyridostigmine 30mg tid, as well as their usual antiretroviral treatment Receives: Drug: Pyridostigmine tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
CD4+ Cell Count Change Between Basal and Week 16 of Additive Treatment
Change in total CD4+ T-cell number from baseline to addition of pyridostigmine
Measured: 16 weeks after initiation of pyridostigmine
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2007 (estimated)
- Study startSep 2007
- Primary completionNov 2008
- Study completionJan 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sergio I. Valdés-Ferrer, MD, PhD, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
- Investigators
- Juan Sierra-Madero, MD, Study chair, Dept. of Infectious Diseases, INNSZJorge Alcocer-Varela, MD, Study director, Dept. of Immunology, INNSZSergio I Valdés-Ferrer, MD, PhD, Principal investigator, Dept. of Neurology, INNSZ
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00518154
- Sponsor's protocol ID
- Ref. 1663
- Status last verified
- Oct 2019
- First submitted
- 17 Aug 2007
- Last updated
- 14 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Valdes-Ferrer SI, Crispin JC, Belaunzaran-Zamudio PF, Rodriguez-Osorio CA, Cacho-Diaz B, Alcocer-Varela J, Cantu-Brito C, Sierra-Madero J. Add-on Pyridostigmine Enhances CD4+ T-Cell Recovery in HIV-1-Infected Immunological Non-Responders: A Proof-of-Concept Study. Front Immunol. 2017 Oct 18;8:1301. doi: 10.3389/fimmu.2017.01301. eCollection 2017.
PubMed 29093707
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00518154
- Acronym / sponsor ID
- Ref. 1663
- Conditions
- HIV Infections
- Keywords
- AIDS, Immunological non-responders, Neuroimmune modulation, Pyridostigmine, Treatment Experienced
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador ZubiranUniversity, hospital or other
- Study start
- Sep 2007
- Primary completion
- Nov 2008 (actual)
- Study completion
- Jan 2009 (actual)
- First posted
- 20 Aug 2007 (estimated)
- Results
- Posted 14 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: Pyridostigmine tabletsPatients will be taking oral Pyridostigmine 30mg tid, as well as their usual antiretroviral treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pyridostigmine tabletsAlso: MestinonPatients will take 30mg tid PO for 12 weeks | Drug | A |
Primary outcome
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29093707Valdes-Ferrer SI, Crispin JC, Belaunzaran-Zamudio PF, Rodriguez-Osorio CA, Cacho-Diaz B, Alcocer-Varela J, Cantu-Brito C, Sierra-Madero J. Add-on Pyridostigmine Enhances CD4+ T-Cell Recovery in HIV-1-Infected Immunological Non-Responders: A Proof-of-Concept Study. Front Immunol. 2017 Oct 18;8:1301. doi: 10.3389/fimmu.2017.01301. eCollection 2017.
- Institute's web pageLink provided by the sponsor.
Related trials for HIV Infections
Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juan Sierra-Madero, MD study chair
Dept. of Infectious Diseases, INNSZ
Jorge Alcocer-Varela, MD study director
Dept. of Immunology, INNSZ
Sergio I Valdés-Ferrer, MD, PhD principal investigator
Dept. of Neurology, INNSZ
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pyridostigmine tablets in people with HIV Infections, run by Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran at 2 sites in Mexico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CD4+ Cell Count Change Between Basal and Week 16 of Additive Treatment (time frame: 16 weeks after initiation of pyridostigmine). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00518154, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2019.