Terazosin randomised pilot

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Jordan Schultz, Nandakumar Narayanan, Michael Welsh and colleagues, University of Iowa. Parkinsonism & Related Disorders 94:79–83, published online 27 November 2021. Registry NCT03905811 (Phase 1/2; started 24 September 2019, completed November 2020).

What happened

Terazosin, a prostate drug, activates the energy enzyme PGK1 in animals and was linked to lower Parkinson's risk in some health records (landmark 208). This pilot tested whether it does the same job in people.

• Design. Randomised, triple-blind, placebo-controlled, one site. Terazosin 5 mg or placebo at bedtime for 12 weeks. Ages 40–90, Hoehn and Yahr stage I–III, on stable medication. 13 randomised (8 terazosin, 5 placebo); recruitment stopped early because of COVID-19.
• Target engagement. In the brain (31P magnetic resonance spectroscopy), the ratio of beta-ATP to inorganic phosphate rose significantly more on terazosin than on placebo, and whole-blood ATP also rose more (p < 0.01 per the abstract). The abstract gives no effect sizes.
• Tolerability. Registry results: 7 of 8 on terazosin reported dizziness or light-headedness versus 1 of 5 on placebo, and 2 had orthostatic hypotension (a standing drop in blood pressure) versus none; 3 on terazosin stopped treatment; no falls and no serious adverse events.

Why it moved us toward a cure

It is the first randomised human data behind landmark 208. It showed an approved drug can move the proposed target in people. That justified bigger trials, including terazosin as an arm of the UK platform trial (landmark 80; Phase 3, NCT07207057, about 1,200 people, recruiting since September 2025). Dizziness at 5 mg is a real limit in older people.

Outcome

Open. This pilot was not built or powered to show slowing. A further Iowa Phase 1/2 trial (NCT07288450) is listed as withdrawn, with no participants, because it was not funded. A 120-person Phase 2 (TZPD2, NCT07464028; PI Ergun Uc) is suspended ("study not funded") with a start now estimated for July 2028. The platform trial (NCT07207057; UCL; terazosin and telmisartan arms against placebo) started 12 September 2025 and is recruiting, with primary completion estimated May 2031.

Sources

• Schultz et al., Parkinsonism Relat Disord 2022;94:79–83, DOI 10.1016/j.parkreldis.2021.11.022, PMID 34894470 (abstract read via Europe PMC)
• ClinicalTrials.gov NCT03905811 (posted results read, API, 19 Oct 2026)
• NCT07207057, NCT07288450, NCT07464028
• Not yet verified: the size of the ATP changes (full text not read); the terazosin dose and design of the platform arm.