Vagus nerve effects on gut bacteria and inflammation in people living with HIV
Effects of Vagal Dysfunction on Gastrointestinal and Inflammatory Pathways in HIV
This project will test whether pyridostigmine pills and gentle non-invasive vagus nerve stimulation can reduce small intestinal bacterial overgrowth and lower inflammation in adults living with well-controlled HIV.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 207 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Icahn School of Medicine at Mount Sinai Academic / other |
| Drugs / interventions | CART |
| Locations | 1 site (New York, New York) |
| Trial ID | NCT04353778 on ClinicalTrials.gov |
What this trial studies
This Phase 1–2 study will first characterize links between vagus nerve dysfunction, small intestinal bacterial overgrowth (SIBO), gastrointestinal transit, and blood markers of inflammation in adults with HIV and matched HIV-negative controls. About 150 people living with HIV and 100 HIV-negative controls will undergo autonomic function testing, hydrogen/methane breath testing for SIBO, wireless motility capsule testing for gut transit and pH, blood draws for inflammatory mediators, and stool and oral microbiome sampling. From the HIV cohort, participants with vagal dysfunction and SIBO or prolonged small-bowel transit will be enrolled into an intervention phase testing oral pyridostigmine and non-invasive vagus nerve stimulation versus placebo. The project combines observational mechanistic work with a randomized treatment component to see if targeting vagal pathways improves gut microbial imbalance and inflammation.
Who should consider this trial
Good fit: Ideal candidates are adults with documented HIV who are on stable antiretroviral therapy, virologically suppressed (HIV-1 RNA <100 copies/mL), and without other known causes of autonomic or gastrointestinal dysfunction.
Not a fit: People with other causes of autonomic or GI dysfunction (for example Parkinson disease, diabetes, recent GI surgery, known obstructive GI disease), uncontrolled HIV, or on excluded medications are unlikely to benefit from participation.
Why it matters
Potential benefit: If successful, the treatments could reduce gut bacterial overgrowth and inflammation and improve gastrointestinal symptoms and long-term health in people living with HIV.
How similar studies have performed: Prior work has linked vagal dysfunction to SIBO and inflammation in people with HIV, but using pyridostigmine or non-invasive vagus nerve stimulation for this purpose is relatively novel and has limited prior clinical trial evidence.
Eligibility criteria
Show full inclusion / exclusion criteria
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 or GI effects (e.g. sympathomimetics, prokinetics, anti-diarrheals, antibiotics) * Urine test negative for stimulants and opiates/opioids and pregnancy test (if applicable) Exclusion Criteria: * Dysphagia to food or pills * Known or suspected obstructive disease of the GI tract (e.g. bezoar, strictures, fistulae, physiologic GI obstruction) * GI surgery within 3m, Crohn's disease, diverticulitis, any electromechanical medical device (e.g. pacemaker, infusion pump). * Contraindication to pyridostigmine (e.g. mechanical intestinal or urinary obstruction, hypersensitivity to pyridostigmine, cardiac arrhythmias, asthma, chronic obstructive pulmonary disease); use of pyridostigmine within the past 6m. * History of intracranial aneurysm/hemorrhage, brain tumor, abnormal neck anatomy, or implants or metal hardware near site of stimulation; exposure to VNS within the past 6m.
Where this trial is running
New York, New York
- Icahn School of Medicine at Mount Sinai — New York, New York, United States (Recruiting)
Study contacts
- Principal investigator: Jessica Robinson-Papp, MD — Icahn School of Medicine at Mount Sinai
- Study coordinator: Niyati Neupane
- Email: niyati.neupane@mssm.edu
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.