Zinc and Diabetes in Patients With Thalassemia: a Pilot Study

• ClinicalTrials.gov Identifier: NCT01772680
• Recruitment Status: Completed
• First Posted: January 21, 2013
• Last Update Posted: November 24, 2020
• Sponsor: UCSF Benioff Children's Hospital Oakland
• Information provided by (Responsible Party): UCSF Benioff Children's Hospital Oakland

Tracking Information

• First Submitted Date: January 17, 2013
• First Posted Date: January 21, 2013
• Last Update Posted Date: November 24, 2020
• Study Start Date: November 2012
• Actual Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 18, 2013)

Oral glucose Tolerance Test [ Time Frame: 3 months ]

Effect of 3 months of zinc supplementation on oral glucose tolerance test results

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 18, 2013)

Fructosamine [ Time Frame: 3 months ]

Determine the effect of 3 months of zinc supplementation on fructosamine levels

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Zinc and Diabetes in Patients With Thalassemia: a Pilot Study
• Official Title: Zinc and Diabetes in Patients With Thalassemia: a Pilot Study
• Brief 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.

Detailed 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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Other
• Condition: Thalassemia

Intervention

Dietary Supplement: Zinc Supplementation

25 mg elemental zinc taken as zinc sulfate in capsule form taken daily for 3 months

Study Arms

Experimental: Zinc Supplementation

25 mg elemental Zinc as Zn sulfate in capsule form taken daily for 3 months

Intervention: Dietary Supplement: Zinc Supplementation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 18, 2013): 40
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: May 2015
• Actual Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• patients diagnosed with transfusion dependent thalassemia
• > 12 years of age

Exclusion Criteria (for both cross-sectional and interventional studies)

• patients who are pregnant
• patients who are on growth hormone therapy

Exclusion criteria (for intervention study only)

• patients who currently have diabetes (therefore cannot have an oral glucose tolerance test)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01772680
• Other Study ID Numbers: 2012-071
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: UCSF Benioff Children's Hospital Oakland
• Original Responsible Party: Ellen B. Fung, UCSF Benioff Children's Hospital Oakland, Associate Research Scientist
• Current Study Sponsor: UCSF Benioff Children's Hospital Oakland
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Ellen B Fung, PhD RD; UCSF Benioff Children's Hospital Oakland

• PRS Account: UCSF Benioff Children's Hospital Oakland
• Verification Date: November 2020