Microtrials
  • Project: Microtrials
  • Lead: Prof K Dhaliwal, Prof JK Baillie
  • Start date: 1 September 2021
  • PSH Theme: Therapeutics

Early evaluation of efficacy

The microtrials concept will test tiny doses of potential therapies in multiple areas of the lungs of critically ill patients.

Advantages:

  • minimal risk of harm to the patient
  • directly measure effect on key endopoint: oxygenation function
  • determine efficacy with only 15 patients

We are developing molecular imaging and characterization tools for alveolar injury and endothelial injury and cellular dysfunction which will be translated into the intensive care unit.

We have created a collection of fluorescent molecular reagents that can individually and specifically detect macrophage activation, neutrophil function, cathepsin activity, endothelial leak, cell damage and T-cell granzyme activity.

In combination with optical endomicroscopy, we will be able to rapidly profile the injury and the inflammatory response in the lungs of patients.

In intubated patients, novel therapeutics can be delivered efficiently to small bronchi feeding a tiny fraction (1%) of the patient’s lung. Alveolar inflammatory imaging and oxygenation measurement using novel thin endobronchial fibres enable serial measurements of the effect of treatment.

Since both the intervention and the endpoint can be measured endoscopically, single experiments can in theory be conducted in the smallest accessible bronchus. This enables in vivo screening in critically-ill humans. Since only a small fraction of lung is treated, there is minimal risk of harm