Effects of Vagal Dysfunction on Gastrointestinal and Inflammatory Pathways in HIV
Icahn School of Medicine at Mount Sinai
Summary
The study team's prior research has shown that dysfunction of a specific nerve, called the vagus nerve, is associated with small intestinal bacterial overgrowth (SIBO), and that SIBO is associated with signs of inflammation in the blood of people living with HIV (PLWH). This research will explore pathways linking vagal dysfunction to inflammation in HIV, focusing on the gastrointestinal tract, and study whether a medication called pyridostigmine and stimulation of the vagus nerve are beneficial therapies.
Description
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. Hypo…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria : * Greater than or equal to18 years old (18 to 64 Years, 65 Years and Over) * Documentation of HIV-1 infection * Stable CART for greater or equal to 3 months * HIV-1 viral load \<100 copies/ml (within 3m) * No diagnosis known to cause autonomic or GI dysfunction other than HIV (e.g. Parkinson's disease, diabetes, peptic ulcer disease, infectious diarrhea) * Willing to refrain from nicotine use for 24h prior to all testing * No contraindication to autonomic testing (e.g. uncontrolled glaucoma, heart rate not under sinus control) * No medications with significant autonomic o…
Interventions
- DrugPyridostigmine
Eight weeks of low-dose pyridostigmine
- DrugPlacebos
matching placebo x 8 weeks
- Procedurenon-invasive vagal nerve stimulation
stimulation of the vagus nerve
Location
- Icahn School of Medicine at Mount SinaiNew York, New York