For Research & Educational Discussion Only. Not Medical Advice
Twenty-eight-residue neuropeptide
Also known as VIP, Aviptadil, RLF-100
A well characterised endogenous neuropeptide with an enormous basic literature, and a clinical history dominated by one contested and heavily publicised COVID-19 programme.
HSDAVFTDNYTRLRKQMAVKKYLNSILNIn shortA signalling peptide found throughout the gut, lungs and nervous system, where it widens blood vessels, opens airways and adjusts immune responses. The basic science on it is vast and long predates any interest in it as a treatment. Its recent public profile comes almost entirely from a synthetic version trialled for respiratory failure in COVID-19.
VIP is a 28-amino-acid neuropeptide found throughout the gut, lungs and nervous system, where it acts as a vasodilator, a bronchodilator and an immune modulator. The basic science on it is vast, over fourteen thousand papers, and long predates any interest in it as a therapy.
Its recent public profile comes almost entirely from aviptadil, a synthetic form trialled for respiratory failure in COVID-19. That programme was accompanied by unusually assertive public claims, and the regulatory outcome did not match them. Anyone reading about VIP now is mostly reading the residue of that episode.
In shortIt acts on two receptors, raising a common internal signalling molecule. In the lung it concentrates in the cells that make surfactant, which is the reasoning behind the lung injury work: protect those cells and you may preserve surfactant production. Around the body it strongly widens blood vessels, which is both how it works and the thing that limits the dose.
Acts at VPAC1 and VPAC2 receptors, raising intracellular cAMP. In the lung it is concentrated in alveolar type II cells, which is the rationale for the acute lung injury work: protecting those cells is a plausible route to preserving surfactant production.
Systemically it is a potent vasodilator, which is both the mechanism and the dose-limiting problem.
In shortA huge amount of basic science, and modest registered clinical work by comparison, mostly in lung conditions. The COVID-19 programme is the case study in reading past a press release: public claims about survival were not matched by any regulatory finding, and emergency authorisation was not granted. The trials are in the registry and that is the appropriate source.
Extensive mechanistic and physiological literature. Registered clinical work is modest by comparison and centres on pulmonary indications, including pulmonary arterial hypertension, sarcoidosis and acute respiratory distress.
The COVID-19 programme is the case study in reading past a press release. Claims made publicly about survival benefit were not matched by a regulatory finding, and emergency use authorisation was not granted. The trials are in the registry and are the appropriate source; contemporaneous reporting about them mostly is not.
In shortLow blood pressure and flushing follow directly from its blood-vessel-widening action and are what limits the dose. Diarrhoea is common, which fits its normal job in the gut. It disappears from the bloodstream very quickly, so how it is formulated and delivered dominates the practical safety picture as much as the molecule does.
Hypotension and flushing follow directly from the vasodilatory mechanism and are the dose-limiting effects. Diarrhoea is common, consistent with its physiological role in the gut.
Its half-life in circulation is very short, which is why formulation and route dominate the practical safety picture as much as the molecule does.
In shortThe synthetic form holds rare-disease designation in some countries but is not approved for general use, and emergency authorisation for COVID-19 was not granted in the US. Material sold under this name outside those programmes is research-use-only, and the sequence is easy to state and hard to manufacture consistently.
Aviptadil holds orphan designation in some jurisdictions but is not approved for general use, and emergency authorisation for COVID-19 respiratory failure was not granted in the United States.
Material sold as VIP outside those programmes is research-use-only. The 28-residue sequence is easy to state and difficult to manufacture to a consistent standard.
1 study indexed. Findings and limitations get equal weight, on purpose.
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Everything above is free to read. What an account opens is the evidence underneath it: 1 study with their limitations, and the regimen each trial actually reported.
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The wider literature
15 indexed papers and 21 registered trials mentioning Vasoactive Intestinal Peptide, straight from PubMed and ClinicalTrials.gov. 18 of 21 administer it; the rest measure it. These have not been read by us. Unlike the studies above, they carry no findings and no limitations written by anyone here, because writing either would mean claiming a reading nobody has done. They are a starting point for yours.
APR Applied Pharma Research s.a.NCT04453839
expanded_accessno longer available
University of Maryland, Baltimore2026NCT06735950
interventionalnanot yet recruitingn=200
University Of Perugia2023NCT05958914
interventionalnaunknownn=45
APR Applied Pharma Research s.a.2021NCT05137795
interventionalphase3withdrawnn=0
APR Applied Pharma Research s.a.2021NCT04360096
interventionalphase2phase3terminatedn=144
National Institute of Allergy and Infectious Diseases (NIAID)2021NCT04843761
interventionalphase3completedn=473
Centurion Pharma2021NCT04844580
interventionalphase2completedn=80
National Institute of Allergy and Infectious Diseases (NIAID)2021NCT06729606
interventionalphase3completedn=471
PhaseBio Pharmaceuticals Inc.2020NCT04433546
interventionalphase2terminatedn=54
Danish Headache Center2020NCT04260035
interventionalnacompletedn=21
Danish Headache Center2019NCT03989817
interventionalnacompletedn=12
PhaseBio Pharmaceuticals Inc.2018NCT03556020
interventionalphase2terminatedn=35
PhaseBio Pharmaceuticals Inc.2017NCT03315507
interventionalphase1completedn=3
Medical College of Wisconsin2012NCT01563757
observationalcompletedn=20
Glostrup University Hospital, Copenhagen2011NCT01471990
interventionalnacompletedn=24
Samsung Medical Center2006NCT00418535
interventionalphase2completed
Danish Headache Center2004NCT00272896
interventionalnacompletedn=12
Clinvest2004NCT00208065
interventionalphase4completedn=50
Medical University of Vienna2003NCT00464932
observationalcompletedn=34
Danish Headache Center2003NCT00255320
interventionalnacompletedn=12
Stony Brook University1998NCT00004494
interventionalphase1completedn=18
Chanchalani GIndian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine2025PMID 41368453
editorial
Youssef JG, et al.Critical care medicine2022PMID 36044317
journal articlemulticenter studyrandomized controlled trialresearch support, non-u.s. gov't
Mukherjee T, et al.Environmental science and pollution research international2022PMID 34846667
journal articlereview
Couvineau A, et al.Frontiers in endocrinology2020PMID 33101216
editorialintroductory journal article
Frye BC, et al.The New England journal of medicine2020PMID 32579820
case reportsletter
Duncan C, et al.World journal of urology2019PMID 30895359
journal articlesystematic review
Deng G, et al.Neurological research2017PMID 27786097
journal articlereview
Gross PC, et al.Journal of pharmaceutical and biomedical analysis2014PMID 24176753
comparative studyjournal articleresearch support, non-u.s. gov't
Passemard S, et al.Current pharmaceutical design2011PMID 21524251
journal articlereview
Mucke HACurrent opinion in investigational drugs (London, England : 2000)2008PMID 18729002
journal articlereview
Leuchte HH, et al.The European respiratory journal2008PMID 18978135
journal article
Igarashi H, et al.The Journal of pharmacology and experimental therapeutics2005PMID 15994369
journal article
Keijzers GBCurrent opinion in investigational drugs (London, England : 2000)2001PMID 11566015
journal articlereview
Pozo D, et al.Immunology today2000PMID 10637552
journal articlereview
Rosselin G, et al.Molecular and cellular endocrinology1982PMID 6290287
journal articlereview
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For Research & Educational Discussion Only. Not Medical Advice
This guide is educational reference material compiled from published literature. It is not medical advice, not a recommendation, and not a substitute for a clinician who knows your history. Nothing here should be used to make a decision about your own health without one.
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