Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01772680 |
| Other study ID # |
2012-071 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 2012 |
| Est. completion date |
May 2015 |
Study information
| Verified date |
November 2020 |
| Source |
UCSF Benioff Children's Hospital Oakland |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The primary aim of this study is to measure zinc status and related proteins in patients with
Thalassemia who have or do not have diabetes. The secondary aim will be to explore the effect
of zinc supplementation on glucose metabolism in patients with thalassemia.
Description:
Patients with Thalassemia major (Thal) require frequent blood transfusions and are at risk
for iron overload. High tissue iron increases the risk of various endocrinopathies, including
diabetes, as well as cardiovascular disease, and infections due to the formation of free
radicals. This systemic condition of oxidative stress elicits an antioxidant response to
reduce tissue damage. Zinc is an important component of that response because it can compete
with iron for multiple cellular binding sites and, therefore, reduce the redox-cycling of
iron and minimize iron-mediated oxidation of lipids, proteins, and DNA.
In Thal patients with chronic hepatic iron overload, tissue zinc redistribution is likely to
be persistent. This could create an unbalanced tissue zinc distribution with excessive
amounts in the liver and deficient levels in other tissues altering zinc-dependent functions,
such as growth, skeletal development, immunity, and glucose regulation. There is a rich body
of literature focused on the 'diabetogenic effects' of altered zinc status which will be
reviewed herein. Our group has recently shown that supplementation with 25 mg/d of zinc can
improve bone density in patients with Thal. This provides evidence for a functional zinc
deficiency, which may also affect other whole body zinc functions, such as insulin secretion
and glucose homeostasis.
Our hypothesis is that hepatic iron overload induces a sub-clinical inflammatory response
that alters the expression of MT and zinc-transport proteins leading to hepatic zinc
sequestration, and an associated zinc-depletion in other tissues. Marginal zinc depletion in
turn leads to increased oxidative stress, cellular apoptosis and altered glucose homeostasis
and insulin secretion. This proposal will focus on cross-sectional differences in markers of
glucose homeostasis and zinc status in diabetic and non-diabetic Thal patients, combined with
a short- term zinc supplementation to explore the effect on glucose and insulin homeostasis.
