NCT04725253

Nicotinamide to Prevent Delirium

Status unknown NA Last updated 26 January 2021

What this trial tests

NA trial testing Nicotinamide in Delirium Confusional State in 146 participants. Status unknown.

Timeline

21 January 2021

Primary endpoint
1 April 2022

30 April 2022

Quick facts

Lead sponsor	University of Chile
Phase	NA
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	prevention
Enrollment	146
Start date	21 January 2021
Primary completion	1 April 2022
Estimated completion	30 April 2022
Sites	1 location across Chile

Drugs / interventions tested

• Nicotinamide (Nicotinamide) — full drug profile →
• Placebo tablets — full drug profile →

Conditions studied

• Delirium Confusional State — all drugs for Delirium Confusional State →

Sponsor

University of Chile

Who can join

65 and older, any sex, with Delirium Confusional State. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Delirium is defined as an acute change in mental status characterized by fluctuating disturbances of consciousness, attention, cognition, and perception, usually secondary to acute injuries such as trauma or infections. Delirium is more frequent in older adults, and is associated with important poor clinical outcomes including increased mortality, functional deterioration, and higher expenditures for healthcare systems.

Although it is not the only one responsible, the inflammatory response plays a key role in the development of delirium. From the first descriptions of the condition 2500 years ago, it is known that patients who present with inflammatory injuries such as trauma (pe. hip fracture) or infections (sepsis), frequently develop delirium. Microglia, are an inflammatory cell with phagocytic capacity, that inhabit the nervous system and have a critical role in the regulation of the inflammatory response in the brain. It is known that microglia have receptors that respond to systemic inflammatory mediators by generating new inflammatory mediators that exert their effect on other glial cells and neurons in the central nervous system, affecting their function. Mouse models have shown that depleting the brain of microglia prevents cognitive decline after a traumatic bone injury, suggesting a role of these cells in the development of delirium.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme that participates in DNA repair, and in the regulation of the expression of inflammatory mediators by immune cell. In vitro experiments have shown that PARP-1 enhances the microglial response to inflammation, and data from mice exposed to the bacterial component "lipo-poly-saccharide (LPS)", a classical model of delirium, showed that pharmacological inhibition of PARP-1 prevents cognitive decline secondary to that injury. Interestingly, nicotinamide, a vitamin widely available in the market, with a well-known safety profile in humans, is a well-recognized inhibitor of PARP-1. The role of PARP-1 nor nicotinamide in delirium has never been explored.

Considering that, 1) there is evidence showing that PARP-1 may act as an enhancer of the inflammatory response of microglia and 2) the protective effect against cognitive impairment produced by pharmacological inhibition of PARP-1 in a mice model of delirium, we propose as hypothesis that PARP-1 participates in delirium pathogenesis by enhancing microglial activation in response to systemic inflammation. To address this hypothesis in patients, we propose to determine in a randomized clinical trial whether nicotinamide, a pharmacological inhibitor of PARP-1, is more effective than placebo for the prevention of delirium in older adults with requirement of oxygen (non-invasive) and suspected coronavirus disease (COVID-19) under study.

The results of this research will contribute significantly in the field of delirium, improving the knowledge of its physiopathology, as well with the development of of new alternatives for its prevention in clinical practice.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.