Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02102737 |
| Other study ID # |
C13-14 |
| Secondary ID |
2013-003526-92 |
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
May 13, 2014 |
| Est. completion date |
March 2018 |
Study information
| Verified date |
August 2021 |
| Source |
Institut National de la Santé Et de la Recherche Médicale, France |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Insulin resistance is closely associated with apparition of type 2 diabetes mellitus; it is
an independent risk factor and predicts future cardiovascular events.
Hyperinsulinemic euglycemic clamp is a validated method to assessment of insulin resistance
and It is also the gold standard technique. However, the complexity and length of this
technique render it unsuitable for routine clinical use.
In this study, the investigators use a new technique to provide precise, objective, fast and
automated quantification of insulin resistance with camera SPECT.
They compare the results with those of the measurement of hyperinsulinemic euglycemic clamp
in population with or without insulin resistance.
The proposed study is to validate this new non-invasive imaging technique for evaluation of
insulin resistance in patients with or without insulin resistance with a comparison with
hyperinsulinemic euglycemic clamp.
Description:
Currently, type II diabetes mellitus, has reached epidemic levels in the world. Moreover, the
prediction for the year 2030 is even more alarming. Insulin resistance, characterized by a
depressed cellular sensitivity to insulin in insulin-sensitive organs, is a central feature
of the metabolic syndrome and a risk factor for type 2 diabetes. Its appearance may precede
the diagnosis of true diabetes several years. Insulin resistance results in decreased
membrane translocation of GLUT-4, whole the molecular mechanism remains unclear. Currently,
there is no simple tool to measure insulin resistance. The gold standard technique remains
the hyperinsulinemic euglycemic clamp. However, the complexity and length of this technique
render it unsuitable for routine clinical use. Many methods or index have been proposed to
assess insulin resistance in human, but none have shown enough relevance to be used in
clinical use. Moreover, all these clinical measurements focus on whole-body glucose uptake,
however an accurate and convenient procedure for insulin resistance measurement by organ
would be interesting. Indeed there are increasingly evidences to insulin resistance as a
primary etiologic factor in the development of nonischemic heart failure (HF), another
growing public health problem.
Nuclear imaging provides interesting methods to measure insulin resistance using Positron
Emission Tomographic (PET) tracer. Two glucose analogs [18F]2-fluoro-2-deoxy-D-glucose (FDG)
and [11Cl-30methyl-n-glucose (3-OMG) have been used to evaluate noninvasively the cellular
uptake of glucose using PET techniques for several organs like heart, skeletal muscle
blood-brain barrier, and liver. [18F] 2-fluoro-2-deoxy-D-glucose (FDG), the most commonly
used to study glucose metabolism in humans, allows the estimation of glucose transport and
its phosphorylation. A number of kinetic modeling approaches have been used for the
quantitation of glucose utilization rates using FDG. FDG is transported and phosphorylated as
native glucose, but calculation of glucose uptake and metabolism requires the use of
correction factors for each process merged into a lumped constant. The major limitation of
these approaches is that quantification of glucose metabolism requires the knowledge of the
lumped constant, a factor, which relates the kinetic behavior of FDG to naturally occurring
glucose in terms of the relative affinity of each molecule for the trans-sarcolemmal
transporter and for hexokinase. Unfortunately, the value of the lumped constant in humans
under different physiological and pathophysiological conditions varies, and metabolic imaging
with PET need standardization of metabolic conditions by hyperinsulinaemic euglycaemic clamp.
3-OMG appears as an ideal glucose analog to probe transmembrane transport. However, due to
the short half-life of the 11C (t1/2 = 20 min), this analog can be used only in clinical
institutions in close proximity of a cyclotron and which have access to PET devices.
According to these knowledge, the investigators have developed an original compound, [123I]
6-deoxy-6-iodo-D-glucose (6DIG), as a tracer of glucose transport equivalent to 3-OMG, the
reference tracer. 6-DIG has previously been exploited to measure IR in vivo and the
investigators transfer to human this measurement technique, perfectly validated in animal.
Previous, they have reported the first use a potential single-photon emission computed
tomography (SPECT) tracer to study basal and insulin-stimulated glucose transport
non-invasively. In a phase I of development, they use a new nuclear probe using an iodinated
tracer of glucose transport for clinical application and specific imaging processing to
assess cardiac insulinoresistance in healthy or diabetic subjects. The results in human
subjects show that this technique rapidly provides insulinoresistance index (ratio
scintigraphy measurement of glucose transport in heart before and after infusion of insulin)
in a simple procedure, opening up new opportunities for screening for pre-diabetic patients.
