Clinical trial NCT03851055: Zinc Supplementation in Patients With β-Thalassemia Major Complicated With Diabetes Mellitus
Official title: Effect of Zinc Supplementation on Glucose Homeostasis in Patients With β-Thalassemia Major Complicated With Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Beta-thalassemia Major Complicated With Diabetes
Keywords: Zinc
blood glucose
diabetes
beta thalassemia
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2019-02-22
Enrollment: 80
Sex: ALL
Minimum age (years): 10
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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:

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

Eligibility criteria: 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.

Primary outcomes:
measure: Fasting blood glucose mg/dl
timeFrame: 12 weeks
Secondary outcomes:
measure: HbA1c%
timeFrame: 12 weeks
measure: fructosamine mg/dl
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Nancy Elbarbary
Study officials:
References:
citation: Gamberini MR, Fortini M, De Sanctis V, Gilli G, Testa MR. Diabetes mellitus and impaired glucose tolerance in thalassaemia major: incidence, prevalence, risk factors and survival in patients followed in the Ferrara Center. Pediatr Endocrinol Rev. 2004 Dec;2 Suppl 2:285-91.
citation: Capdor J, Foster M, Petocz P, Samman S. Zinc and glycemic control: a meta-analysis of randomised placebo controlled supplementation trials in humans. J Trace Elem Med Biol. 2013 Apr;27(2):137-42. doi: 10.1016/j.jtemb.2012.08.001. Epub 2012 Nov 6.
citation: Fung EB, Kwiatkowski JL, Huang JN, Gildengorin G, King JC, Vichinsky EP. Zinc supplementation improves bone density in patients with thalassemia: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 2013 Oct;98(4):960-71. doi: 10.3945/ajcn.112.049221. Epub 2013 Aug 14.