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Hi All,
Can anyone tell me about the value-add, a euglycemic/hyperglycemic
clamp study gives to a molecule under Phase I/II development. Is the
clamp study routinely done for oral anti-diabetics during clinical
development? Any expert review articles on the role of clamp studies
in clinical development?
Regards
Dr Srinivas Sidgiddi
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The following message was posted to: PharmPK
Dear Srinivas,
the euglycemic/hyperinsulinemic clamp is probably the most important
test in studing glucose homeostasis both in humans and in animals. In
brief, it consists in continuosly infuse a dose of insulin aimed to
reach a fixed level (e.g. hyperinsulinemia) in plasma. Together with
insulin, somatostatin is co-infused to block insulin secretion from
pancreas which may alter the fixed clamp level. Obviously, the high
level of insulin will result in a decrease of glycemia (hypoglycemia)
that will be prevented by infusing glucose (25%) to restore
euglycemia (90 mg/dl). The insulin-resistant animal or human, for
example, will require a lower rate of glucose infusion to maintain
euglycemia since insulin has a lower effect on them.
With the aim of a trace infusion of tritiated glucose, which do not
have to alter the glycemia, is it possible to quantify endogenous
(mainly liver) glucose production (which is increased in diabetes) or
peripheral glucose disposal (decreased in diabetes). To finish, there
are also pancreatic clamps and hyperglycemic clamps, in the latter
glucose is infused to reach hyperglycemia and insulin secretion rate
quantified to measure beta-cell performances.
The importance of this test make it a must in order to characterize
the efficacy for an oral anti-diabetics both in pre-clinical (rats
and monkeys) and during clinical development
Of course, in not a routinely done test but the majority of the
endocrinology units are used to performe it for research purposes.
Bye
Dr Roberto Conti
Sigma-Tau
Dep. of Endocrinology and Metabolism
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