Effects of Vagal Dysfunction on Gastrointestinal and Inflammatory Pathways in HIV

NCT04353778 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: GCO 18-28121R01DK122853-01A1
• Study Type: interventional
• Target: 207
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV; Non-HIV; Vagus Nerve Dysfunction

Keywords

Small intestinal bacterial overgrowth; People living with HIV; HIV-associated autonomic neuropathy; Distal symmetric polyneuropathy

Outcome Measures

Primary Outcomes (4)

• Small bowel transit time (SBTT)

  Small bowel transit time (SBTT) measured by wireless motility capsule (wmc, smartpill)

  8 weeks

• Gastric pH measurement

  Gastric pH measurement measured by wireless motility capsule (wmc, smartpill)

  8 weeks

• Hydrogen/methane breath testing (hbt)

  hydrogen/methane breath testing (hbt) to measure small intestinal bacterial overgrowth

  8 weeks

• IL6 measurement [Time Frame: 5 years]

  8 weeks

Study Arms (5)

PLWH

NO INTERVENTION

People living with HIV (HIV)

Healthy Controls

NO INTERVENTION

Healthy controls who do not have HIV

Pyridostigmine

ACTIVE COMPARATOR

PLWH on pyridostigmine 30mg PO TID

Drug: Pyridostigmine

Placebo

PLACEBO COMPARATOR

PLWH on placebo

Drug: Placebos

nVNS

OTHER

PLWH to undergo non-invasive vagal nerve stimulation

Procedure: non-invasive vagal nerve stimulation

Interventions

Pyridostigmine DRUG

Eight weeks of low-dose pyridostigmine

Pyridostigmine

Placebos DRUG

matching placebo x 8 weeks

Placebo

non-invasive vagal nerve stimulation PROCEDURE

stimulation of the vagus nerve

Also known as: nVNS

nVNS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

Related Publications (6)

• Robinson-Papp J, Nmashie A, Pedowitz E, George MC, Sharma S, Murray J, Benn EKT, Lawrence SA, Machac J, Heiba S, Kim-Schulze S, Navis A, Roland BC, Morgello S. The effect of pyridostigmine on small intestinal bacterial overgrowth (SIBO) and plasma inflammatory biomarkers in HIV-associated autonomic neuropathies. J Neurovirol. 2019 Aug;25(4):551-559. doi: 10.1007/s13365-019-00756-9. Epub 2019 May 16.

  PMID: 31098925 BACKGROUND

• Carod-Artal FJ. Infectious diseases causing autonomic dysfunction. Clin Auton Res. 2018 Feb;28(1):67-81. doi: 10.1007/s10286-017-0452-4. Epub 2017 Jul 20.

  PMID: 28730326 BACKGROUND

• Robinson-Papp J, Nmashie A, Pedowitz E, Benn EKT, George MC, Sharma S, Murray J, Machac J, Heiba S, Mehandru S, Kim-Schulze S, Navis A, Elicer I, Morgello S. Vagal dysfunction and small intestinal bacterial overgrowth: novel pathways to chronic inflammation in HIV. AIDS. 2018 Jun 1;32(9):1147-1156. doi: 10.1097/QAD.0000000000001802.

  PMID: 29596112 BACKGROUND

• Paulon E, Nastou D, Jaboli F, Marin J, Liebler E, Epstein O. Proof of concept: short-term non-invasive cervical vagus nerve stimulation in patients with drug-refractory gastroparesis. Frontline Gastroenterol. 2017 Oct;8(4):325-330. doi: 10.1136/flgastro-2017-100809. Epub 2017 May 24.

  PMID: 29067158 BACKGROUND

• Lerman I, Hauger R, Sorkin L, Proudfoot J, Davis B, Huang A, Lam K, Simon B, Baker DG. Noninvasive Transcutaneous Vagus Nerve Stimulation Decreases Whole Blood Culture-Derived Cytokines and Chemokines: A Randomized, Blinded, Healthy Control Pilot Trial. Neuromodulation. 2016 Apr;19(3):283-90. doi: 10.1111/ner.12398. Epub 2016 Mar 15.

  PMID: 26990318 BACKGROUND

• Tarn J, Legg S, Mitchell S, Simon B, Ng WF. The Effects of Noninvasive Vagus Nerve Stimulation on Fatigue and Immune Responses in Patients With Primary Sjogren's Syndrome. Neuromodulation. 2019 Jul;22(5):580-585. doi: 10.1111/ner.12879. Epub 2018 Oct 17.

  PMID: 30328647 BACKGROUND

MeSH Terms

Interventions

Pyridostigmine Bromide

Intervention Hierarchy (Ancestors)

Pyridinium Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jessica Robinson-Papp, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Niyati Neupane

CONTACT

niyati.neupane@mssm.edu

Mary Catherine George, MM, PhD

CONTACT

212-241-0784; mary-catherine.george@mssm.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 17, 2020
• First Posted: April 20, 2020
• Study Start: August 3, 2020
• Primary Completion (Estimated): September 16, 2026
• Study Completion (Estimated): September 16, 2026
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Beginning 3 months and ending 5 years following article publication.
• Access Criteria: Anyone who wishes to access the data. Data will be published.

Locations

US (1)