Effects of Vagal Dysfunction on Gastrointestinal and Inflammatory Pathways in HIV (EVA)
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|ClinicalTrials.gov Identifier: NCT04353778|
Recruitment Status : Recruiting
First Posted : April 20, 2020
Last Update Posted : April 13, 2022
|Condition or disease||Intervention/treatment||Phase|
|HIV Non-HIV Vagus Nerve Dysfunction||Drug: Pyridostigmine Drug: Placebos Procedure: non-invasive vagal nerve stimulation||Phase 1 Phase 2|
Objectives Aim 1: To elucidate mechanisms linking VD, SIBO and chronic inflammation in PLWH. PLWH (N=150) will undergo autonomic function tests (AFTs) for VD, hydrogen/methane breath testing (HBT) for SIBO, Wireless Motility Capsule (WMC, SmartPill) testing for GI transit times and pH measurements, blood draw for quantification of inflammatory mediators, and collection of stool samples and oral swabs for characterization of the GI microbiome.
Hypothesis 1a (primary): The relationship between VD and SIBO in HIV is mediated by prolonged small bowel transit time (SBTT) and hypochlorhydria.
Hypothesis 1b (exploratory): There is an additional pathway linking VD and elevated IL-6 in PLWH which is independent of SIBO and bacterial translocation.
Aim 2: To determine whether the relationship between VD and SIBO is modified by the presence of HIV-infection. HIV-infection results in disruption of the GI mucosal barrier,5 which could make PLWH more vulnerable to adverse GI effects of VD. HIV-uninfected controls (N=100), age and gender matched to the PLWH from Aim 1, will undergo the same assessment as the PLWH. The study team will test for effect modification of the VD-SIBO relationship by HIV status, using logistic regression to examine the interaction between VD and HIV.
Aim 3: To establish vagal pathways as a viable treatment target for individuals with well-controlled HIV. PLWH with VD, SIBO and/or prolonged SBTT (N=96) will be identified from the Aim 1 cohort. The first 86 eligible patients will be randomized to 8 weeks of pyridostigmine versus placebo; the remaining 10 will receive 8 weeks of open-label noninvasive vagal nerve stimulation (nVNS) to assess feasibility. All patients will then be retested (AFTs, HBT, SmartPill, blood draw, stool samples and oral swabs).
Hypothesis 3a (primary): Eight weeks of low-dose pyridostigmine (30mg PO TID) will reduce SIBO as compared to placebo in PLWH. Hypothesis 3b (exploratory): Non-invasive VNS is safe, well tolerated and acceptable to PLWH.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||250 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Effects of Vagal Dysfunction on Gastrointestinal and Inflammatory Pathways in HIV|
|Actual Study Start Date :||August 3, 2020|
|Estimated Primary Completion Date :||April 2024|
|Estimated Study Completion Date :||April 2024|
No Intervention: PLWH
People living with HIV (HIV)
No Intervention: Healthy Controls
Healthy controls who do not have HIV
Active Comparator: Pyridostigmine
PLWH on pyridostigmine 30mg PO TID
Eight weeks of low-dose pyridostigmine
Placebo Comparator: Placebo
PLWH on placebo
matching placebo x 8 weeks
PLWH to undergo non-invasive vagal nerve stimulation
Procedure: non-invasive vagal nerve stimulation
stimulation of the vagus nerve
Other Name: nVNS
- Small bowel transit time (SBTT) [ Time Frame: 5 years ]Small bowel transit time (SBTT) measured by wireless motility capsule (wmc, smartpill)
- Gastric pH measurement [ Time Frame: 5 years ]Gastric pH measurement measured by wireless motility capsule (wmc, smartpill)
- Hydrogen/methane breath testing (hbt) [ Time Frame: 5 years ]hydrogen/methane breath testing (hbt) to measure small intestinal bacterial overgrowth
- IL6 measurement. [Time Frame: 5 years] [ Time Frame: 5 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04353778
|Contact: Alexandra Nmashie, MD||212-241-3193||Alexandra.firstname.lastname@example.org|
|Contact: Mary Catherine George, MM, PhDemail@example.com|
|United States, New York|
|Icahn School of Medicine at Mount Sinai||Recruiting|
|New York, New York, United States, 10029|
|Contact: Alexandra Nmashie, MD 212-241-3193 Alexandra.firstname.lastname@example.org|
|Contact: Mary Catherine George, MM,PhD 212-241-0784 email@example.com|
|Principal Investigator: Jessica Robinson- Papp, MD|
|Principal Investigator:||Jessica Robinson-Papp, MD||Icahn School of Medicine at Mount Sinai|