Glucose Clamp Study [PK / PD]

posted by ElMaestro  – Belgium?, 2020-07-21 10:24 (99 d 22:56 ago) – Posting: # 21765
Views: 1,621

Hi VijithRoy,


» Am new to this field, Can anyone please describe about the technique on How it works? Principle ? For in which case it is been used ? Applications?
»
» What is the main concept and learning part we should get thorough in it ?


the idea of the glucose clamp is straightforward:
Human's have a tendency to keel over and expire rapidly if their glucose levels get too low. Imagine you can give a constant infusion of glucose to keep the glucose constant in blood. I.e. you seek to ascertain that whatever glucose disappears from the blood is matched by the glucose appearing. That is the principle of the (euglycemic) clamp and it will work for situtions when "something" (see example 2 below) could otherwise cause blood glucose to drop dangerously.

So under a running clamp you need to constantly measure blood glucose and you constantly need to adapt and adjust the glucose infusion rate to keep the level constant at a safe level / in a well defined window.

Examples of application:
  1. Insulin resistance. The need for glucose infusion is low(er), because cells don't use of the glucose in the blood. The insulin does not help glucose away from the blood and into the cells, so to say.
  2. BE of a newly formulated long-acting insulin: You give a dose of the insulin. Now, then due to the effect of glucose you put the subject under a clamp, to keep glucose levels up and safe. During the clamp you measure the new insulin levels as primary for AUC and Cmax, but you can also measure AUC of glucose and other stuff as a secondary.
The idea is simple and it works great. However, the technical difficulty is considerable: It is not easy to constantly measure glucose in blood. This, however simple it may sound, is annoyingly error-prone. There is measurement error, but also a lot of error due to blood's natural tendency to clot (you do not really measure it is plasma or serum). There is no noninvasive technique for it (one company uses a noninvasive technique to approximate blood levels by interstitial levels of glucose, but it isn't exactly the same, and it does not respond rapidly to changes in the blood levels).

So glucose clamp = one subject, one glucose infusion pump + a lot of staff members who are constantly occupied taking invasive measurements of blood glucose and adjusting the glucose infusion pump accordingly.
All this is done in the usual phase I setup with extra vigilance for spotting hypo events. At a lab you may need an immuno-assay for measurements of the new insulin if that's what you are doing, and those measurements are also associated with various annoying pitfalls, of course.
(For starters: Your standards may need to be in horse blood or horse serum, now, try and think which authority would accept that for a small synthetic molecule in a normal BE trial?).

I could be wrong, but...

Best regards,
ElMaestro

No, of course you do not need to audit your CRO if it was inspected in 1968 by the agency of Crabongostan.

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