Autonomic Neuropathy, GI Motility, and Inflammation in HIV

NCT02850276 | Completed Early Phase 1 Results DMC

• 2 other identifiers: GCO 14-14541R21DK105917-01A1
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to explore a possible link between the autonomic nervous system and immune function in patients with HIV. Sometimes HIV can cause these nerves to function abnormally, this is called HIV-associated autonomic neuropathy (HIV-AN). HIV-AN is a condition that is different from person to person. In some people it causes no symptoms and is not harmful, in others it may cause symptoms such as dizziness or lightheadedness, nausea, vomiting, diarrhea, constipation, or problems urinating. Most people with HIV-AN don't know that they have it. One of the important nerves in the autonomic nervous system is the vagus nerve. Abnormal function of the vagus nerve may cause stomach and intestinal slowing, which could lead to an overgrowth of bacteria. The body senses these bacteria and tries to fight them, leading to inflammation. In this study the researchers will test whether abnormal function of the vagus nerve in HIV is associated with stomach slowing and overgrowth of bacteria, and if a drug called pyridostigmine can help.

Conditions

HIV Disease

Keywords

HIV disease; gastrointestinal problems

Outcome Measures

Primary Outcomes (2)

• Change in Breath Test

  Breath Test at week 8 as compared to baseline. Breath test results is the rise in the combined hydrogen and methane during the breath test.

  baseline and week 8

• Number of Participants With Reduction in Small Intestinal Bacterial Overgrowth (SIBO)

  Number of participants with reduction in Small intestinal bacterial overgrowth (SIBO) assessed with breath testing after 8 weeks of treatment. The hydrogen breath test for the detection of small intestinal bacterial overgrowth (SIBO), obtained by having participants exhale into a plastic bag. the hydrogen content of the samples is measured using a commercially available analyzer.

  week 8

Secondary Outcomes (6)

• Mean Percent Retention of Gastric Contents on Gastric Emptying Study

  Baseline and week 8

• Change in sCD14 Level

  Baseline and week 8

• Change in TNFα Level

  Baseline and week 8

• Change in IL-6 Plasma Level

  Baseline and week 8

• The Composite Autonomic Symptom Score (COMPASS)

  Baseline and week 8

Study Arms (1)

Pyridostigmine

EXPERIMENTAL

30mg PO three times a day

Drug: Pyridostigmine

Interventions

Pyridostigmine DRUG

Also known as: Pyridostigmine Bromide, Mestinon, Regonol, Gravitor

Pyridostigmine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years old
• Documented evidence of HIV-1 infection
• Stable CART therapy for ≥3 months Most recent HIV-1 viral load ≤100 copies/ml (value must be within the past six months)
• English speaking
• Able to tolerate autonomic testing (e.g. able to stand, able to perform Valsalva maneuver).
• If using nicotine-containing products willing to refrain from use for 24 hours prior to all testing procedures (autonomic reflex screen, breath testing, and gastric emptying)
• ≥1 GI symptom on the Survey of Autonomic Symptoms (SAS)47

You may not qualify if:

• Diagnosis known to cause autonomic dysfunction other than HIV (e.g. Parkinson's disease, diabetes)
• Diagnosis known to cause GI dysfunction other than HIV (e.g. peptic ulcer disease, infectious diarrhea)
• Current use of any of the following classes of medications (due to potential for significant autonomic or GI effects, interaction with pyridostigmine, or interference with one or more of the testing procedures) Prokinetics (e.g. metoclopramide) Anti-diarrheals (e.g. loperamide) Antibiotics Mefloquine
• Medical or psychiatric conditions precluding safe participation in study procedures or deemed likely to result in hospitalization during the study period.
• The presence of one or more of the following diagnoses which render the Valsalva maneuver relatively or absolutely contraindicated: uncontrolled glaucoma, aortic stenosis, myocardial infarction in the last 6 months, other retinopathy or unclipped cerebral aneurysm.
• The presence of one or more of the following diagnoses which impede interpretation of autonomic testing: cardiac arrhythmias or pacemakers.
• An allergy to eggs (contraindication to gastric emptying scintigraphy)
• Any of the following laboratory results:
• Positive pregnancy test (administered to women of childbearing potential only) Urine toxicology screen positive for stimulants (e.g. amphetamines, cocaine) or opiates/opioids.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• National Institutes of Health (NIH): collaborator
• 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

Location

Related Publications (5)

• Deeks SG, Tracy R, Douek DC. Systemic effects of inflammation on health during chronic HIV infection. Immunity. 2013 Oct 17;39(4):633-45. doi: 10.1016/j.immuni.2013.10.001.

  PMID: 24138880 BACKGROUND

• Marchetti G, Cozzi-Lepri A, Merlini E, Bellistri GM, Castagna A, Galli M, Verucchi G, Antinori A, Costantini A, Giacometti A, di Caro A, D'arminio Monforte A; ICONA Foundation Study Group. Microbial translocation predicts disease progression of HIV-infected antiretroviral-naive patients with high CD4+ cell count. AIDS. 2011 Jul 17;25(11):1385-94. doi: 10.1097/QAD.0b013e3283471d10.

  PMID: 21505312 BACKGROUND

• Robinson-Papp J, Sharma S, Simpson DM, Morgello S. Autonomic dysfunction is common in HIV and associated with distal symmetric polyneuropathy. J Neurovirol. 2013 Apr;19(2):172-80. doi: 10.1007/s13365-013-0160-3. Epub 2013 Apr 12.

  PMID: 23580249 BACKGROUND

• Robinson-Papp J, Sharma SK. Autonomic neuropathy in HIV is unrecognized and associated with medical morbidity. AIDS Patient Care STDS. 2013 Oct;27(10):539-43. doi: 10.1089/apc.2013.0188. Epub 2013 Sep 13.

  PMID: 24032624 BACKGROUND

• George NS, Sankineni A, Parkman HP. Small intestinal bacterial overgrowth in gastroparesis. Dig Dis Sci. 2014 Mar;59(3):645-52. doi: 10.1007/s10620-012-2426-7. Epub 2012 Oct 5.

  PMID: 23053897 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Pyridostigmine Bromide

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Limitations include difficulty with recruitment resulting in small sample size, and lack of placebo control.

Results Point of Contact

• Title: Dr. Jessica Robinson-Papp
• Organization: Icahn School of Medicine at Mount Sinai

jessica.robinson-papp@mssm.edu

212-241-8390

Study Officials

• Jessica Robinson-Papp, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 27, 2016
• First Posted: July 29, 2016
• Study Start: November 1, 2015
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: May 29, 2019
• Results First Posted: May 29, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)