HIV-1-infectionPhase 2NCT03312244
Pyridostigmine as Immunomodulator in People Living With HIV
A Phase 2 study testing Pyridostigmine Bromide in people with HIV-1-infection and CD4+ T Lymphocytopenia, run by Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran at 1 site in Mexico.
Trial summary
Human immunodeficiency virus (HIV) infection is characterized by persistent immune activation and a constant turnover of T cells. This leads to a precipitous fall in the number of T cells, as well as to an early immunosenescence. This results in increased susceptibility to opportunistic infections. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV-1-infection, CD4+ T Lymphocytopenia, Immune Deficiency
- What is being tested?
- Pyridostigmine Bromide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteMexico
- Study dates
- 1 Jul 2019to 30 Jun 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 stable ART for at least six months
- At least two undetectable viral load determinations in the previous six months
- Patient agrees to participate and signs informed consent
Who cannot join
- Concomitant active infectious or neoplastic disease
- History of new AIDS-defining events in the previous six months
- If a participant is female, pregnancy or breast-feeding
- Exposure to an investigational agent, chemotherapy or radiotherapy within the previous 28 days
- Currently taking or planning to take treatment for Tuberculosis
- Being unable to follow or comply with the protocol interventions
- The participant is receiving immunosuppressive treatment, including corticosteroids
Trial locations and contacts
1 site in 1 country.
Mexico1 site
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Mexico City, Tlalpan, 14080
About this study
Official title: Study of the Role of Peripheral Acetylcholinesterase Inhibitor Pyridostigmine as Immunomodulators in a Population of Patients Living With Human Immunodeficiency Virus Infection.
Human immunodeficiency virus (HIV) infection is characterized by persistent immune activation and a constant turnover of T cells. This leads to a precipitous fall in the number of T cells, as well as to an early immunosenescence. This results in increased susceptibility to opportunistic infections. In these patients, modulation of the immune response represents a promising mechanism to maintain immunological homeostasis and prevent the development of pathology. We hypothesize that the addition of pyridostigmine to the regular combined antiretroviral therapy will result in a decrease in T cell overactivation and a reduction in circulating inflammatory markers.
Read the detailed description
Human immunodeficiency virus (HIV) infection is a public health problem with enormous personal, and social losses. According to the National Mexican HIV/AIDS survey, more than 235,000 new cases of HIV infection were reported in Mexico between 1983 and 2015.
HIV infection is characterized by persistent immune activation and a constant turnover of T cells. This leads to a precipitous fall in the number of CD4+ and CD8+ T cells, as well as to early immunosenescence. This immunosenescence results in increased susceptibility to opportunistic infections and a profound decrease in circulating and mucosal T cells. In these patients, modulation of the immune response represents a promising mechanism to maintain immunological homeostasis and prevent the development of pathology. From this perspective, it is posible that a reduced immune activation -rather than accelerating the progression of infection- may be an important factor in controlling infection and delaying the progression from chronic infection to acquired immunodeficiency syndrome (AIDS).
The administration of combined antiretroviral therapy (cART) has resulted in a reduction in the mortality of these patients, although the occurrence of late morbidity due to both infection and treatment has increased. Unfortunately, even in countries with complete coverage for HIV-infection, a large group of patients do not start treatment until late stages, in which immunosenescence is profound and the possibilities of immunological recovery (increase in T cell counts CD4+, normalization of the CD4+/CD8+ index, decrease in susceptibility to opportunists, normalization in the cellular response to vaccines) are very low. In this context, finding new immuno-modulatory strategies that are both easily applicable and potentially improving survival and quality of life is crucial.
The therapeutic use of neuroimmune regulators in HIV infection has been poorly explored. The nervous system has evolutionary mechanisms of reflex control of the inflammatory response, such as cholinergic anti-inflammatory pathway. Cholinergic stimulation through the use of nicotinic agonists has shown promising effects in murine and cellular models of systemic inflammation. Since cholinergic agonists are rapidly degraded or cause side effects, we performed a pilot study using pyridostigmine (Mestinon®), an acetylcholinesterase inhibitor (ACh-E), in HIV-infected patients. We observed that administration of pyridostigmine decreases the activation and proliferation of HIV-infected T cells, reduces the production of interferon (IFN)-γ and increases that of interleukin (IL)-10 (Valdés-Ferrer SI et al., AIDS Research And Human Retrovir 2009). In a second open-label pilot study in seven chronically infected patients with full virologic suppression but without concomitant elevation of CD4+ T cell counts, we found that the addition of pyridostigmine to ART led to a sustained and significant increase in the number of CD4 + T cells (PRS record: NCT00518154; Valdés-Ferrer SI, et al., Frontiers in Immunology, 2017). These results suggest that the addition of pyridostigmine to antiretroviral therapy may be beneficial in achieving and maintaining immunological homeostasis in patients with HIV.
The present study will address the potential effectiveness of add-on pyridostigmine (180mg, once per day, P.O.) on CD4+ T cell counts, CD4+/CD8+ ratio, as well as ex-vivo markers of T cell phenotype and activity. The study is designed as a 24-week crossover study where patients will start a 12-week of pyridostigmine or placebo, and then crossing-over for an additional 12 weeks (placebo-to-pyridostigmine, and pyridostigmine-to-placebo).
Since pyridostigmine is a commonly used drug for both myasthenia gravis and as a preventive in biological warfare cases, if our hypotheses are correct, the results can be easily extrapolated to clinical practice, as there is enough long-term evidence of utility and safety of the drug.
- Being tested
- Pyridostigmine Bromide, Placebo
- Medical subject headings
- T-Lymphocytopenia, Idiopathic CD4-Positive, Immunologic Deficiency Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pyridostigmine BromideDrug
Also called Mestinon Timespan
Pyridostigmine 180mg/day p.o.
PlaceboDrug
Also called Starch (pharmaceutical grade)
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Pyridostigmine | Experimental | Pyridostigmine 180mg/d slow-release formulation Receives: Drug: Pyridostigmine Bromide |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
CD4+ T cell count
Change in total CD4+ T cel count from baseline
Measured: Change from baseline, at 12 and 24 weeks
Secondary outcomes (4)
soluble CD14 receptor
Change in circulating (plasma) soluble CD14 receptor from baseline
Measured: Change from baseline, at 12 and 24 weeks
CD4+ / CD8+
Change in index of CD4+ to CD8+ T cells from baseline
Measured: Change from baseline, at 12 and 24 weeks
Inteleukin (IL)-6
Change in circulating (plasmatic) IL-6 from baseline
Measured: Change from baseline, at 12 and 24 weeks
TREC levels
Changes in T cell receptor excision DNA circle (TREC) levels
Measured: Change from baseline, at 12 and 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2017
- Study start1 Jul 2019
- Primary completion30 Jun 2021 (estimated)
- Study completion30 Jun 2022 (estimated)
Why it stopped: Due to COVID-19, effective 3/19/2020 recruitment is halted until further notice
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for HIV-1-infectionStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 12x12 weeks of pyridostigmine or placebo followed by crossing-over to the other arm of intervention
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
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 director, INNSZ
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03312244
- Sponsor's protocol ID
- Ref. 1873
- Status last verified
- Apr 2020
- First submitted
- 1 Apr 2017
- Last updated
- 10 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All data will be freely available to all research parties involved
Publications
Autran B, Carcelain G, Li TS, Blanc C, Mathez D, Tubiana R, Katlama C, Debre P, Leibowitch J. Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science. 1997 Jul 4;277(5322):112-6. doi: 10.1126/science.277.5322.112.
PubMed 9204894Pakker NG, Notermans DW, de Boer RJ, Roos MT, de Wolf F, Hill A, Leonard JM, Danner SA, Miedema F, Schellekens PT. Biphasic kinetics of peripheral blood T cells after triple combination therapy in HIV-1 infection: a composite of redistribution and proliferation. Nat Med. 1998 Feb;4(2):208-14. doi: 10.1038/nm0298-208.
PubMed 9461195Kaufmann GR, Perrin L, Pantaleo G, Opravil M, Furrer H, Telenti A, Hirschel B, Ledergerber B, Vernazza P, Bernasconi E, Rickenbach M, Egger M, Battegay M; Swiss HIV Cohort Study Group. CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: the Swiss HIV Cohort Study. Arch Intern Med. 2003 Oct 13;163(18):2187-95. doi: 10.1001/archinte.163.18.2187.
PubMed 14557216Corbeau P, Reynes J. Immune reconstitution under antiretroviral therapy: the new challenge in HIV-1 infection. Blood. 2011 May 26;117(21):5582-90. doi: 10.1182/blood-2010-12-322453. Epub 2011 Mar 14.
PubMed 21403129Moore DM, Hogg RS, Yip B, Wood E, Tyndall M, Braitstein P, Montaner JS. Discordant immunologic and virologic responses to highly active antiretroviral therapy are associated with increased mortality and poor adherence to therapy. J Acquir Immune Defic Syndr. 2005 Nov 1;40(3):288-93. doi: 10.1097/01.qai.0000182847.38098.d1.
PubMed 16249702Piconi S, Trabattoni D, Gori A, Parisotto S, Magni C, Meraviglia P, Bandera A, Capetti A, Rizzardini G, Clerici M. Immune activation, apoptosis, and Treg activity are associated with persistently reduced CD4+ T-cell counts during antiretroviral therapy. AIDS. 2010 Aug 24;24(13):1991-2000. doi: 10.1097/QAD.0b013e32833c93ce.
PubMed 20651586Tracey KJ. Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest. 2007 Feb;117(2):289-96. doi: 10.1172/JCI30555.
PubMed 17273548Valdes-Ferrer SI, Crispin JC, Belaunzaran PF, Cantu-Brito CG, Sierra-Madero J, Alcocer-Varela J. Acetylcholine-esterase inhibitor pyridostigmine decreases T cell overactivation in patients infected by HIV. AIDS Res Hum Retroviruses. 2009 Aug;25(8):749-55. doi: 10.1089/aid.2008.0257.
PubMed 19645607Ku NS, Song YG, Han SH, Kim SB, Kim HW, Jeong SJ, Kim CO, Kim JM, Choi JY. Short communication: factors influencing time to CD4(+) T cell counts >200 cells/mm(3) in HIV-infected individuals with CD4(+) T cell <50 cells/mm(3) at the time of starting combination antiretroviral therapy. AIDS Res Hum Retroviruses. 2012 Dec;28(12):1594-7. doi: 10.1089/AID.2011.0282. Epub 2012 Jun 25.
PubMed 22632127Kawashima K, Fujii T. The lymphocytic cholinergic system and its biological function. Life Sci. 2003 Mar 28;72(18-19):2101-9. doi: 10.1016/s0024-3205(03)00068-7.
PubMed 12628464Rosas-Ballina M, Olofsson PS, Ochani M, Valdes-Ferrer SI, Levine YA, Reardon C, Tusche MW, Pavlov VA, Andersson U, Chavan S, Mak TW, Tracey KJ. Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science. 2011 Oct 7;334(6052):98-101. doi: 10.1126/science.1209985. Epub 2011 Sep 15.
PubMed 21921156Valdes-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 10 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Role of Peripheral Acetylcholinesterase Inhibitor Pyridostigmine as Immunomodulators in a Population of Patients Living With Human Immunodeficiency Virus Infection.
- ClinicalTrials.gov ID
- NCT03312244
- Acronym / sponsor ID
- Ref. 1873
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Due to COVID-19, effective 3/19/2020 recruitment is halted until further notice
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador ZubiranUniversity, hospital or other
- Study start
- 1 Jul 2019 (actual)
- Primary completion
- 30 Jun 2021 (estimated)
- Study completion
- 30 Jun 2022 (estimated)
- First posted
- 17 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Human immunodeficiency virus (HIV) infection is characterized by persistent immune activation and a constant turnover of T cells. This leads to a precipitous fall in the number of T cells, as well as to an early immunosenescence. This results in increased susceptibility to opportunistic infections. In these patients, modulation of the immune response represents a promising mechanism to maintain immunological homeostasis and prevent the development of pathology. We hypothesize that the addition of pyridostigmine to the regular combined antiretroviral therapy will result in a decrease in T cell overactivation and a reduction in circulating inflammatory markers.
Detailed description
Human immunodeficiency virus (HIV) infection is a public health problem with enormous personal, and social losses. According to the National Mexican HIV/AIDS survey, more than 235,000 new cases of HIV infection were reported in Mexico between 1983 and 2015.
HIV infection is characterized by persistent immune activation and a constant turnover of T cells. This leads to a precipitous fall in the number of CD4+ and CD8+ T cells, as well as to early immunosenescence. This immunosenescence results in increased susceptibility to opportunistic infections and a profound decrease in circulating and mucosal T cells. In these patients, modulation of the immune response represents a promising mechanism to maintain immunological homeostasis and prevent the development of pathology. From this perspective, it is posible that a reduced immune activation -rather than accelerating the progression of infection- may be an important factor in controlling infection and delaying the progression from chronic infection to acquired immunodeficiency syndrome (AIDS).
The administration of combined antiretroviral therapy (cART) has resulted in a reduction in the mortality of these patients, although the occurrence of late morbidity due to both infection and treatment has increased. Unfortunately, even in countries with complete coverage for HIV-infection, a large group of patients do not start treatment until late stages, in which immunosenescence is profound and the possibilities of immunological recovery (increase in T cell counts CD4+, normalization of the CD4+/CD8+ index, decrease in susceptibility to opportunists, normalization in the cellular response to vaccines) are very low. In this context, finding new immuno-modulatory strategies that are both easily applicable and potentially improving survival and quality of life is crucial.
The therapeutic use of neuroimmune regulators in HIV infection has been poorly explored. The nervous system has evolutionary mechanisms of reflex control of the inflammatory response, such as cholinergic anti-inflammatory pathway. Cholinergic stimulation through the use of nicotinic agonists has shown promising effects in murine and cellular models of systemic inflammation. Since cholinergic agonists are rapidly degraded or cause side effects, we performed a pilot study using pyridostigmine (Mestinon®), an acetylcholinesterase inhibitor (ACh-E), in HIV-infected patients. We observed that administration of pyridostigmine decreases the activation and proliferation of HIV-infected T cells, reduces the production of interferon (IFN)-γ and increases that of interleukin (IL)-10 (Valdés-Ferrer SI et al., AIDS Research And Human Retrovir 2009). In a second open-label pilot study in seven chronically infected patients with full virologic suppression but without concomitant elevation of CD4+ T cell counts, we found that the addition of pyridostigmine to ART led to a sustained and significant increase in the number of CD4 + T cells (PRS record: NCT00518154; Valdés-Ferrer SI, et al., Frontiers in Immunology, 2017). These results suggest that the addition of pyridostigmine to antiretroviral therapy may be beneficial in achieving and maintaining immunological homeostasis in patients with HIV.
The present study will address the potential effectiveness of add-on pyridostigmine (180mg, once per day, P.O.) on CD4+ T cell counts, CD4+/CD8+ ratio, as well as ex-vivo markers of T cell phenotype and activity. The study is designed as a 24-week crossover study where patients will start a 12-week of pyridostigmine or placebo, and then crossing-over for an additional 12 weeks (placebo-to-pyridostigmine, and pyridostigmine-to-placebo).
Since pyridostigmine is a commonly used drug for both myasthenia gravis and as a preventive in biological warfare cases, if our hypotheses are correct, the results can be easily extrapolated to clinical practice, as there is enough long-term evidence of utility and safety of the drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 12x12 weeks of pyridostigmine or placebo followed by crossing-over to the other arm of intervention
| Arm | Type | Receives |
|---|---|---|
| Pyridostigmine | Experimental | Drug: Pyridostigmine BromidePyridostigmine 180mg/d slow-release formulation |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- HIV-1 infected subjects 18 years of age or older
- Receiving stable ART for at least six months
- At least two undetectable viral load determinations in the previous six months
- Patient agrees to participate and signs informed consent
Key exclusion criteria (7 listed)
- Concomitant active infectious or neoplastic disease
- History of new AIDS-defining events in the previous six months
- If a participant is female, pregnancy or breast-feeding
- Exposure to an investigational agent, chemotherapy or radiotherapy within the previous 28 days
- Currently taking or planning to take 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 BromideAlso: Mestinon TimespanPyridostigmine 180mg/day p.o. | Drug | Pyridostigmine |
| PlaceboAlso: Starch (pharmaceutical grade)Placebo | Drug | Placebo |
Primary outcome
CD4+ T cell count
Time frame: Change from baseline, at 12 and 24 weeks
Change in total CD4+ T cel count from baseline
4 secondary outcomes
soluble CD14 receptor
Time frame: Change from baseline, at 12 and 24 weeks
CD4+ / CD8+
Time frame: Change from baseline, at 12 and 24 weeks
Inteleukin (IL)-6
Time frame: Change from baseline, at 12 and 24 weeks
TREC levels
Time frame: Change from baseline, at 12 and 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2020.
- Results publication: PubMed 9204894Autran B, Carcelain G, Li TS, Blanc C, Mathez D, Tubiana R, Katlama C, Debre P, Leibowitch J. Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science. 1997 Jul 4;277(5322):112-6. doi: 10.1126/science.277.5322.112.
- Results publication: PubMed 9461195Pakker NG, Notermans DW, de Boer RJ, Roos MT, de Wolf F, Hill A, Leonard JM, Danner SA, Miedema F, Schellekens PT. Biphasic kinetics of peripheral blood T cells after triple combination therapy in HIV-1 infection: a composite of redistribution and proliferation. Nat Med. 1998 Feb;4(2):208-14. doi: 10.1038/nm0298-208.
- Results publication: PubMed 14557216Kaufmann GR, Perrin L, Pantaleo G, Opravil M, Furrer H, Telenti A, Hirschel B, Ledergerber B, Vernazza P, Bernasconi E, Rickenbach M, Egger M, Battegay M; Swiss HIV Cohort Study Group. CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: the Swiss HIV Cohort Study. Arch Intern Med. 2003 Oct 13;163(18):2187-95. doi: 10.1001/archinte.163.18.2187.
- Results publication: PubMed 21403129Corbeau P, Reynes J. Immune reconstitution under antiretroviral therapy: the new challenge in HIV-1 infection. Blood. 2011 May 26;117(21):5582-90. doi: 10.1182/blood-2010-12-322453. Epub 2011 Mar 14.
- Results publication: PubMed 16249702Moore DM, Hogg RS, Yip B, Wood E, Tyndall M, Braitstein P, Montaner JS. Discordant immunologic and virologic responses to highly active antiretroviral therapy are associated with increased mortality and poor adherence to therapy. J Acquir Immune Defic Syndr. 2005 Nov 1;40(3):288-93. doi: 10.1097/01.qai.0000182847.38098.d1.
- Results publication: PubMed 20651586Piconi S, Trabattoni D, Gori A, Parisotto S, Magni C, Meraviglia P, Bandera A, Capetti A, Rizzardini G, Clerici M. Immune activation, apoptosis, and Treg activity are associated with persistently reduced CD4+ T-cell counts during antiretroviral therapy. AIDS. 2010 Aug 24;24(13):1991-2000. doi: 10.1097/QAD.0b013e32833c93ce.
- Results publication: PubMed 17273548Tracey KJ. Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest. 2007 Feb;117(2):289-96. doi: 10.1172/JCI30555.
- Results publication: PubMed 19645607Valdes-Ferrer SI, Crispin JC, Belaunzaran PF, Cantu-Brito CG, Sierra-Madero J, Alcocer-Varela J. Acetylcholine-esterase inhibitor pyridostigmine decreases T cell overactivation in patients infected by HIV. AIDS Res Hum Retroviruses. 2009 Aug;25(8):749-55. doi: 10.1089/aid.2008.0257.
- Results publication: PubMed 22632127Ku NS, Song YG, Han SH, Kim SB, Kim HW, Jeong SJ, Kim CO, Kim JM, Choi JY. Short communication: factors influencing time to CD4(+) T cell counts >200 cells/mm(3) in HIV-infected individuals with CD4(+) T cell <50 cells/mm(3) at the time of starting combination antiretroviral therapy. AIDS Res Hum Retroviruses. 2012 Dec;28(12):1594-7. doi: 10.1089/AID.2011.0282. Epub 2012 Jun 25.
- Results publication: PubMed 12628464Kawashima K, Fujii T. The lymphocytic cholinergic system and its biological function. Life Sci. 2003 Mar 28;72(18-19):2101-9. doi: 10.1016/s0024-3205(03)00068-7.
- Results publication: PubMed 21921156Rosas-Ballina M, Olofsson PS, Ochani M, Valdes-Ferrer SI, Levine YA, Reardon C, Tusche MW, Pavlov VA, Andersson U, Chavan S, Mak TW, Tracey KJ. Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science. 2011 Oct 7;334(6052):98-101. doi: 10.1126/science.1209985. Epub 2011 Sep 15.
- Results publication: 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.
- Individual participant dataSharing planned: Yes. All data will be freely available to all research parties involved
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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 director
INNSZ
1 site 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 Bromide in people with HIV-1-infection and CD4+ T Lymphocytopenia, run by Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran at 1 site 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 4 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: paused, as of the sponsor's last update on 10 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. 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?
Results are not available in the source record.
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+ T cell count (time frame: Change from baseline, at 12 and 24 weeks). 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 NCT03312244, which also lists 12 linked publications.
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 10 Apr 2020.