VIP

VIP, short for vasoactive intestinal peptide, is a signal built from 28 amino acids that arises naturally in the body, one that nerve cells throughout the body use to communicate. Researchers describe it as having broad calming effects on inflammation and immune activity, working through two receptor types found on many different cell types. An injectable form of a similar molecule, aviptadil, showed a promising but mixed signal in a first, smaller trial for severe COVID-19 respiratory failure, but a larger, later trial found no benefit and was stopped early.

What it is

VIP is a signaling peptide the nervous system produces naturally, and it acts on two related receptors, called VPAC1 and VPAC2, that appear on immune cells, blood vessels, and nerve tissue across the body. Because those receptors are so widespread, VIP's proposed effects touch several systems at once: calming inflammatory signaling, relaxing blood vessels, and, when delivered through the nose, potentially reaching brain tissue directly along nerve pathways that bypass the normal blood-brain barrier.

A synthetic, injectable version of VIP called aviptadil has been developed and studied specifically for critical COVID-19 respiratory failure, a use built around VIP's anti-inflammatory activity in the lungs. Separately, and using a different, compounded nasal-spray formulation, some researchers and clinicians have studied VIP as part of a broader research approach to chronic inflammatory response, a proposed reaction some people have to mold and water-damaged buildings; that use has not been tested in a randomized trial identified in the record behind this entry.

How it is studied

The human trial evidence for a VIP-based molecule comes from two randomized, controlled trials of intravenous aviptadil in patients hospitalized with critical COVID-19 respiratory failure. The first, smaller trial compared outcomes over 60 days between treated and placebo groups; a second, larger, government-funded trial in a broader group of patients with COVID-19 lung failure was stopped early by its independent safety board because the drug was judged unlikely to show a benefit. The nasal-spray form used in chronic inflammatory response research has been studied only through smaller case series and clinical experience reports, reflecting its status as a compounded, off-label preparation rather than an approved product.

What studies report

In a 196-patient randomized trial, intravenous aviptadil did not significantly improve the trial's main planned outcome, being alive and off a breathing machine at 60 days, but a secondary measure of 60-day survival favored the drug, with roughly twice the odds of being alive compared with placebo. [1]
That same trial reported no drug-related serious adverse events and described the overall safety profile as acceptable. [1]
A later, larger, 461-patient randomized trial of intravenous aviptadil in patients with COVID-19-associated lung failure found no significant difference from placebo in recovery or survival through 90 days, and the trial's independent monitoring board recommended stopping it for futility before enrollment was complete. [2]

What is not known

The first trial's positive signal was a secondary measure in a relatively small study, and its main planned outcome did not reach statistical significance; researchers described that result as mixed rather than a clear success. The larger, independently monitored follow-up trial then found no benefit at all and was stopped for futility, which weighs against the earlier positive secondary finding. The nasal-spray form used in chronic inflammatory response research rests on an even thinner evidence base than the aviptadil trials, with no randomized trial identified in the record behind this entry.

Regulatory status

The intravenous form of VIP studied for COVID-19, known as aviptadil, received a Fast Track designation from the United States Food and Drug Administration to speed its review process, but that designation falls well short of approval, so the medicine remains unapproved. A compounded VIP nasal spray likewise has no FDA clearance and is used off-label through compounding pharmacies.