VIP

A 28-amino-acid neuropeptide discovered in 1970 that functions as a vasodilator, bronchodilator, immunomodulator, and neurotransmitter. VIP is widely distributed across the central and peripheral nervous systems and the gastrointestinal tract. The synthetic form, aviptadil, received FDA Orphan Drug Designation for ARDS and Fast Track Designation for COVID-19-associated respiratory failure, though the pivotal TESICO trial was stopped for futility.

In the CIRS (Chronic Inflammatory Response Syndrome) and mold illness recovery community, intranasal VIP is the final step (Step 12) of the Shoemaker protocol, discussed in the context of neuroinflammation, grey matter restoration, and immune marker normalization. Independent RCT validation of the CIRS application is lacking.

VIP occupies an unusual position: strong mechanistic rationale across multiple disease areas (PAH, CIRS, neuroinflammation, ARDS) but failure to achieve FDA approval for any indication. The TESICO trial's futility stop was a significant setback for the aviptadil program. In the CIRS community, VIP remains the protocol endpoint peptide prescribed by Shoemaker-trained physicians, with over 10,000 patients reportedly treated, but evidence quality is limited to open-label practitioner-reported data and small prospective studies (e.g., grey matter volume restoration on NeuroQuant MRI).

The 2-minute IV half-life effectively restricts meaningful systemic use to continuous infusion, while the Shoemaker intranasal protocol leverages local mucosal delivery. The FDA's 2019 move to restrict VIP compounding adds regulatory uncertainty for CIRS practitioners.