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

• ClinicalTrials.gov Identifier: NCT03851055
• Recruitment Status: Completed
• First Posted: February 22, 2019
• Last Update Posted: February 25, 2019
• Sponsor: Ain Shams University
• Information provided by (Responsible Party): Nancy Samir Elbarbary, Ain Shams University

Tracking Information

• First Submitted Date: February 21, 2019
• First Posted Date: February 22, 2019
• Last Update Posted Date: February 25, 2019
• Actual Study Start Date: August 1, 2017
• Actual Primary Completion Date: July 10, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 21, 2019)

Fasting blood glucose mg/dl [ Time Frame: 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.

Original Primary Outcome Measures (submitted: February 21, 2019)

Fasting blood glucose [ Time Frame: 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.

• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: February 21, 2019)

• HbA1c% [ Time Frame: 12 weeks ]
  changes in HbA1c% levels
• fructosamine mg/dl [ Time Frame: 12 weeks ]
  changes in fructosamine levels mg/dl

Original Secondary Outcome Measures (submitted: February 21, 2019)

HbA1c% and fructosamine [ Time Frame: 12 weeks ]

changes in HbA1c% levels

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Beta-thalassemia Major Complicated With Diabetes

Intervention

Drug: Zinc

One arm will receive Zinc Second arm will receive placebo

Study Arms

• Active Comparator: intervention group
  will receive zinc supplementation
  Intervention: Drug: Zinc
• No Intervention: Control group
  Patients will receive placebo only

Publications *

• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 21, 2019): 80
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: August 28, 2018
• Actual Primary Completion Date: July 10, 2018 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes

• Ages: 10 Years to 18 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Egypt

Administrative Information

• NCT Number: NCT03851055
• Other Study ID Numbers: Ain shams Pediatrics 3082019
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Patients data and identity are totally anonymous to the study group

• Current Responsible Party: Nancy Samir Elbarbary, Ain Shams University
• Original Responsible Party: Same as current
• Current Study Sponsor: Ain Shams University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Ain Shams University
• Verification Date: February 2019