Zinc as potential co-adjuvant in type-2 diabetes therapy

ISRCTN	ISRCTN95262434
DOI	https://doi.org/10.1186/ISRCTN95262434
Secondary identifying numbers	Fondecyt 1120323

Submission date: 05/02/2016
Registration date: 23/02/2016
Last edited: 22/02/2016

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Diabetes is a condition that causes a person’s blood sugar level to become too high. Insulin is the hormone made by beta-cells in the pancreas and controls the amount of glucose in the blood. In type 2 diabetes, the body does not produce enough insulin for it to work properly or the body cells do not react properly to insulin (insulin resistance). Type-2 diabetes is very common. In Chile, this disease affects almost one-tenth of the adult population. It is a chronic (long lasting) condition responsible for long term-severe dysfunction of several organs (i.e. causes several organs to not work as they should, which can lead to health problems). While there a number of drug treatments available to treat insulin resistance and insulin secretion (how much insulin the body produces), measures to protect the beta-cells producing the insulin are less available. In addition, the use of some nutrients that may protect the function of beta-cells has not fully tested. Given that it mimics the action of insulin, and has antioxidant, anti-inflammatory, apoptosis (cell death), and insulin secretion functions, zinc is an interesting candidate to become a co-adjuvant to diabetes therapy (i.e used to treat diabetes in addition to other treatment). While there are promising results from studies suggesting a potential beneficial effect of increasing the amount of zinc available in both pancreas beta-cells and tissues that insulin is known to act upon, information from human studies is very limited. This research project will address this issue by looking at the effects of the supplementation with zinc on diabetes by comparing insulin secretion and clinical condition of type 2 diabetes patients that take zinc supplements over a two year period compared to those that don’t.

Who can participate?
Adults aged 30-65 with type-2 diabetes.

What does the study involve?
Participants are randomly allocated to one of two groups. Those in group 1 take a zinc tablet once a day for two years. Those in group 2 take a placebo tablet (made from talc) once a day for two years. Insulin resistance and secretion is assessed for all participants after one year and again after two years.

What are the possible benefits and risks of participating?
All patents receive medical control for their diabetes every 4 months during the entire two-year period of at no cost; nutritional advise every 12 months. Risks involved are associated to sampling and lab methods used in the study.

Where is the study run from?
Department of Nutrition, Faculty of Medicine, University of Chile

When is the study starting and how long is it expected to run for?
March 2012 to May 2016

Who is funding the study?
National Commission for Scientific and Technological Research (Chile)

Who is the main contact?
1. Dr Manuel Ruz (scientific)
mruz@med.uchile.cl
2. Mrs Juana Codoceo (public)

Contact information

Dr Manuel Ruz
Scientific

Independencia 1027
Santiago
8380453
Chile

ORCID ID	0000-0001-6010-8409
Phone	56 22978-6134
Email	mruz@med.uchile.cl

Mrs Juana Codoceo
Public

Independencia 1027
Santiago
8380453
Chile

Study information

Study design	Interventional double-blind, controlled, single centre study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Other
Study type	Treatment
Participant information sheet	Not available in web format, please use contact details below to request information sheet
Scientific title	Zinc supplementation in type-2 diabetes: a randomized clinical trial and molecular studies of the mechanisms involved
Study acronym	DAZ (Diabetes and Zinc)
Study objectives	Two-year zinc supplementation in type-2 diabetic individuals will decrease their oxidative stress and inflammatory status leading to enhanced glucose-stimulated insulin secretion and improved clinical and metabolic condition of diabetes when compared with non-treated type-2 diabetic subjects.
Ethics approval(s)	Ethics committee for research in humans of the Faculty of Medicine, University of Chile, 22/03/2012
Health condition(s) or problem(s) studied	Type-2 diabetes
Intervention	Participants will be matched by BMI, age, sex and duration of diabetes, then, allocated into one of the two experimental groups using a double-blind randomized approach. All patients will undergo routine medical controls by Physicians of the Department of Nutrition every 4 months. The supplementation period is 2 years. 1. Experimental group: Participants will receive 30 mg/day of elemental zinc contained in one capsule, which is ~3-4 times the recommended intakes for men and women respectively, but below the upper level of intake (FNB-IOM 2001) in order to avoid any risk of excessive intake. 2. Placebo (Control) Group: Participants will receive one capsule of similar appearance to the Zn group but containing a placebo (talc). The patients will receive a container with 30 capsules (Zn or placebo) to be taken once a day. This container will be replaced monthly. Personnel from the Department of Nutrition will check once a month the number of capsules consumed.
Intervention type	Supplement
Primary outcome measure	1. Insulin secretion assessed by a modified frequently sampled intravenous glucose tolerance test (FSIVGTT) 2. Insulin sensitivity assessed by a modified frequently sampled intravenous glucose tolerance test (FSIVGTT) 3. Fasting glycated haemoglobin by HPLC 4. Plasma glucose, 5. Urinary glucose, and 6. Microalbumin determined by an automated dry-chemistry method Determinations will be carried out before and one and two years after supplementation.
Secondary outcome measures	1. Oxidative stress (plasma isoprostane using the Cayman´s "8-Isoprostane ELISA kit, TBARS by the OxiSelect TBARS Assay kit; red blood cell glutathione by an enzymatic method; glutathione peroxidase activity by means of the Biovision glutathione peroxidase activity colorimetric assay kit") 2. Inflammation markers (plasma ultra sensitive reactive-C protein by an immunoturbidimetric assay;, Adiponectin, IL-6, and IL-1β by means of a microsphere Luminex fluorescent technique 3. Gene expression of selected zinc transporters in peripheral blood mononuclear cells (PBMNC) qPCR using SYBR Green 4. Zn status parameters (plasma and hair zinc) and size of the rapidly exchageable zinc pool (EZP) using Zn stable isotope methodology Determinations will be carried out before and one and two years after supplementation.
Overall study start date	15/03/2012
Completion date	31/05/2016

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	80
Key inclusion criteria	1. Men and women with type-2 diabetes (<10 years since diagnosis) 2. Thirty to 65 years old 3. BMI 20-40 kg/m2 4. Stable body weight (weight variation <5%) for at least 3 months prior to screening 5. Glycated hemoglobin (HbA1c) <9 % and/or fasting glycemia <180 mg/dL
Key exclusion criteria	1. Insulin therapy. 2. History of ketoacidosis or hyperosmolar hyperglycemic nonketotic syndrome in the previous 6 months. 3. Estimated glomerular filtration rate <60 mL/min. 4. Alanine aminotransferase or aspartate aminotransferase >2.5 times the upper normal limit. 5. Congestive heart failure (grade III-IV according to the New York Heart Association criteria, 1994) 6. Uncontrolled hypertension 7. History of stroke, transient ischemic attack or acute myocardial infarction (previous 5 years). Recent surgery or acute infection (previous 3 months) 8. Major psychiatric disorder affecting compliance 9.. Use of antipsychotic medications 10. Systemic use of glucocorticoid steroids within previous 6 weeks 11. Alcohol intake ≥2 drinks/day 12. Cancer diagnosis or treatment in the past 5 years, with the exception of cancers that have been cured, and carry a good prognosis 13. HIV positivity 14. Pregnant or lactating women 15. Having taken vitamins mineral supplements in the previous 3 months
Date of first enrolment	11/10/2012
Date of final enrolment	31/05/2014

Locations

Countries of recruitment

Chile

Study participating centre

Department of Nutrition, Faculty of Medicine, University of Chile

Independencia 1027
Santiago
8380453
Chile

Sponsor information

University of Chile, Faculty of Medicine
University/education

Independencia 1027
Santiago
8380453
Chile

Website	http://www.med.uchile.cl
"ROR"	https://ror.org/047gc3g35

Funders

Funder type

Government

Comisión Nacional de Investigación Científica y Tecnológica
Government organisation / National government

Alternative name(s): National Commission for Scientific and Technological Research, CONICYT
Location: Chile

Results and Publications

Intention to publish date	30/09/2016
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not expected to be made available
Publication and dissemination plan	To be confirmed at a later date
IPD sharing plan