Zinc Supplementation in Patients With β-Thalassemia Major Complicated With Diabetes Mellitus

Sponsor

Ain Shams University (Other)

Overall Status

Completed

CT.gov ID

NCT03851055

Collaborator

(none)

Enrollment

Location

Arms

12.9

Actual Duration (Months)

6.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Beta-thalassemia represents a group of recessive inherited hemoglobin disorders characterized by reduced synthesis of β-globin chain. The homozygous state (β-thalassemia major) "TM" results in severe anemia, which needs regular blood transfusion . The life expectancy in patients with TM has increased due to therapeutically management, such as frequent transfusion, desferal administration and bone marrow transplantation. Diabetes is clinically characterized by hyperglycemia due to either low circulating concentrations of, or decreased sensitivity to, insulin. Patients with TM typically exhibit β-cell or insulin insufficiency, and may develop diabetes due to toxic levels of iron in their pancreas, one of the strongest predictors of β-cell destruction. By contrast, hyperinsulinemia, secondary to insulin resistance, with normal glucose tolerance has also been observed.

The pathogenic mechanisms leading from siderosis to diabetes are poorly understood.

Condition or Disease	Intervention/Treatment	Phase
Beta-thalassemia Major Complicated With Diabetes	Drug: Zinc	Phase 3

Detailed Description

Zinc(Zn) is a critical trace element in human health. Zinc has a potential to be utilized for the treatment of type 2 diabetes; however, evidence suggests that the effect of Zn on type 2 diabetes remains unclear. Up to 85% of the whole body Zn content is found in muscle and bones, with 11% in the skin and liver .Zn is an indispensable co-factor for more than 300 enzymes involved in metabolism and also reportedly plays a role in aging, immune system, apoptosis, and oxidative stress.

Although the effect of zinc supplementation in the improvement of oxidative stress is controversial, one of the causes that the oxidative stress is present in patients with type 2 diabetes is the change in zinc metabolism. Recent studies have demonstrated that the islet-restricted zinc transporter, ZnT8 (SLC30A8), regulates insulin secretion and hepatic insulin clearance, suggesting that Zn is a key biological factor in glucose homeostasis and the risk of developing type 2 diabetes.

In patients without thalassemia, there is a rich body of literature focused on the "diabetogenic effects" of altered zinc status.

Zinc supplementation has even been suggested as an adjunct therapy in the management of non-thalassemia related diabetes .Functional zinc deficiency exists in a contemporary sample of healthy β-thalassemic patients. An estimated 20% to 30% of patients with β-thalassemia are zinc deficient. The high prevalence is thought to be related to a combination of increased urinary losses compounded by elevated requirements.

Glucose homeostasis and its relation to Zinc status has not been widely studied especially in Egyptian children and adolescents with β-thalassemia major.

The aim of this study is to:

Assess zinc status in patients with β-thalassemia major and diabetes mellitus and its relation to clinical and laboratory parameters of these patients.
Effect of zinc supplementation on glucose homeostasis in patients with β-thalassemia major and diabetes mellitus.

Study Design

Study Type:

Interventional

Actual Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Effect of Zinc Supplementation on Glucose Homeostasis in Patients With β-Thalassemia Major Complicated With Diabetes Mellitus

Actual Study Start Date :

Aug 1, 2017

Actual Primary Completion Date :

Jul 10, 2018

Actual Study Completion Date :

Aug 28, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: intervention group will receive zinc supplementation	Drug: Zinc One arm will receive Zinc Second arm will receive placebo
No Intervention: Control group Patients will receive placebo only

Arm

Intervention/Treatment

Active Comparator: intervention group

will receive zinc supplementation

Drug: Zinc

One arm will receive Zinc Second arm will receive placebo

No Intervention: Control group

Patients will receive placebo only

Outcome Measures

Primary Outcome Measures

Fasting blood glucose mg/dl [12 weeks]
the change in fasting blood glucose level after the 12 weeks of treatment in the intervention group when compared to the placebo group.

Secondary Outcome Measures

HbA1c% [12 weeks]
changes in HbA1c% levels
fructosamine mg/dl [12 weeks]
changes in fructosamine levels mg/dl

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with β-thalassemia major and diabetes confirmed by history, examination and investigation.
Patients on regular visits to clinic.
Age more than 10 years old.

Exclusion Criteria:

Those who refused to lay informed consent.
Those below age limit.
Patients with other disorders that may affect glucose homeostasis rather than TM.
Patients with autoimmune disease, collagen diseases, infections, tumors, hematological diseases other than Thalassemia major.