Beta Thalassemia Major Anemia Clinical Trial
Official title:
The Potential Hepatoprotective Effect of Metformin in Patients With Beta Thalasemia Major
Beta Thalassemia is a major public health problem in Mediterranean countries.In Egypt, it is
considered as the most common chronic hemolytic anemia.one of the major complications in this
inherited disorder is iron overload which lead to oxidative stress and tissue damage.
Regarding toxic effect of iron overload on liver, hepatomegaly is one of the most findings
that resulting from hemosiderosis, extra medullary hematopoiesis, transmitted hepatitis B and
C and cirrhosis.
A lot of studies have been carried out recently to study the beneficial role of metformin in
non-diabetic patients of different disorders as non-alcoholic fatty liver disease
(NAFLD).Among several studies, it's demonstrated that metformin significantly improved
insulin resistance, aminotransferase levels and liver morphology.
The role of metformin in these studies is mainly thought to be antioxidant and
anti-inflammatory effects. However, the role of Metformin on hepatic function in different
populations with the same mechanism of liver injury should be further investigated.
This clinical trial will be carried out on 60 patients with beta thalassemia major receiving
regular blood transfusion and iron chelating therapy, either HCV positive or negative
patients.
They will be randomly distributed into either control group (group 1, n=30) receiving blood
transfusion and taking iron chelating therapy or treatment group (group 2, n=30) receiving
blood transfusion and taking iron chelating therapy along with metformin tablets (500
mg/twice daily) for 6 months.
Beta-Thalassemia is a major public health problem in Mediterranean countries , parts of North
and West Africa, the Middle East, the Indian subcontinent, southern Far East and southeastern
Asia is of the highest incidence. In Egypt, it is considered as the most common chronic
hemolytic anemia (85.1%) with 5.3- 9% carrier rate and annual birth of 1000/1.5 million live
births. Thalassemia is a heterogeneous group of hereditary anemia that results from reduced
or absent production of alpha or beta globin chains of hemoglobin A. β-thalassemia patients
have partial or complete lack of production of β-chains of hemoglobin. The remaining excess
of α-chains are unstable, and they finally precipitate and disintegrate, causing red blood
cell (RBC) membrane damage. The affected RBCs are prematurely hemolysed in the spleen and
bone marrow, leading to increased RBC turnover, ineffective erythropoiesis, and severe anemia
that can only be controlled by regular blood transfusion.
One of the major complications in this inherited disorder is iron overload because of
premature hemolysis, ineffective erythropoiesis and repeated transfusion in the plasma and
major organs such as heart, liver, and endocrine glands. Iron has a catalytic role to produce
powerful reactive oxidant species (ROS) and free radicals, which lead to oxidative stress and
damage . Children with beta thalassemia have oxidative stress and antioxidant deficiency even
without iron overload status. The only way to avoid the accumulation of potentially toxic
iron is iron chelation along with the transfusional therapy, desferrioxamine is a chelating
agent that has been discovered 30 years ago and since then it has been considered to be one
of the most important chelating agent that have been extensively used in the clinical
practice . Then other iron chelating agents have been discovered as deferasirox (Exjade®) and
deferiprone (Kelfer®). However, there are a lot of problems regarding the compliance to
desferrioxamine regimen and the side effects of other orally active iron chelating agents,
which rises the need for studying the effect of other naturally occurring iron chelating
agents and supplements to reduce the consequences of the iron overload. As reactive oxygen
species (ROS) and iron overload have an important role in the pathophysiology of thalassemia
, some studies have been carried out to determine the effects of supplements such as
silymarin and vitamin E in thalassemic patients on regular blood transfusion and
desferrioxamine, and they showing benefit due to their antioxidant, cytoprotective, and
iron-chelating activities .
Regarding the toxic effect of iron overload on liver, hepatomegaly is one of the most
findings that resulting from hemosiderosis, extra medullary hematopoiesis, transmitted
hepatitis B and C and cirrhosis . In one study, liver function tests (LFT) and serum ferritin
were elevated in most patients in spite of desferoxamine use .
Metformin (Biguanides) is used as a first-line treatment for patients with type 2 diabetes
mellitus . But it is not the only use of metformin, a lot of studies have been carried out
recently to study the beneficial role of metformin in non-diabetic patients of different
disorders. Metformin was shown to be safe and effective for management of type 2 diabetes in
pediatric patients aged 10-16 years old, initiated dose of 500 mg twice daily and titrated up
to a maximum of 2000 mg/day based on response . Several clinical studies have supported the
beneficial role of metformin in patients with non-alcoholic fatty liver disease (NAFLD) .
Most of these studies have evaluated the effect of different doses of metformin on liver
biochemistry (aminotransferase profile), histology, and metabolic syndrome feature . Among
several studies, it's demonstrated that metformin significantly improved insulin resistance,
aminotransferase levels, and liver morphology. Furthermore, in ob/ob mice, a model of hepatic
steatosis, it has been shown that metformin reversed hepatomegaly, hepatic fat accumulation,
and ALT abnormalities, by reducing hepatic tumor necrosis factor-α (TNF-α) expression . Also
the hepatoprotective effect of metformin on methotrexate-induced hepatotoxicity in rabbits
with acute lymphocytic leukemia (ALL) has been established. The role of metformin in these
studies is mainly thought to be antioxidant and anti-inflammatory effects. However, the role
of Metformin on hepatic function in different populations with the same mechanism of liver
injury should be further investigated.
This study is conducted to determine the safety and efficacy of metformin as hepatoprotective
and antioxidant therapy in iron overloaded patients with Beta-Thalassemia Major.
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