Zinc, Chromium, Vitamin C, and Copper Combination Supplement for Prediabetes Progression

PreDiabetes Clinical Trial

— CHANGE  

Official title:

A Combination of Zinc, Chromium, Vitamin C, and Copper Supplement for Prediabetes Progression: Randomized Controlled-Trial in Jakarta

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04511468
• Other study ID #: CHANGE
• Status: Recruiting
• Phase: Phase 2
• Start date: June 23, 2021
• Est. completion date: March 31, 2025

Study information

• Verified date: May 2024
• Source: Indonesia University
• Contact: Rina Agustina, MD, MSc, PhD
• Phone: +62 21 3912477
• Email: r.agustina[@]ui.ac.id; dr.rinaagustina[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Currently, the incidence of diabetes mellitus is increasing worldwide. People with prediabetes have higher risk to develop diabetes mellitus type 2. Several studies have proven that Zinc and Chromium are minerals that contribute to decreasing the level of blood glucose and insulin resistance. In addition, vitamin C also contributes in decreasing Fasting Blood Glucose (FBG) and Hemoglobin A1c (HbA1c). However, the eficacy of a combined zinc, chromium, vitamin C, and copper (ZCC) in decreasing blood glucose in prediabetic people has never been performed.

The primary objective of this study is to investigate the effect of a combination of ZCC supplementation with standard healthy lifestyle counseling in improving glucose profile [Fasting Blood Glucose (FBG), 2-hour Oral Glucose Tolerance Test (OGTT), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)] from prediabetes to normal or reducing the risk of progression from prediabetes to Type 2-Diabetes Mellitus (T2DM) compared to placebo with standard healthy lifestyle intervention.

Description:

Diabetes is an important public health problem as the number of people with diabetes are increasing across the world and contributes to high mortality burden. Prediabetes is an intermediate stage between normal glucose tolerance and type 2 diabetes mellitus. Furthermore, people with prediabetes have higher risk to develop diabetes mellitus type 2.

There are several objectives in this study, such as primary objective, secondary objectives, and exploratory objectives.

1. Primary Objective:

To investigate the effect of a combination of Zinc, Chromium, Vitamin C, and Copper supplementation (ZCC supplementation) with standard healthy lifestyle intervention in improving glucose profile [Fasting Blood Glucose (FBG), 2-hour Oral Glucose Tolerance Test (OGTT), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)]) from prediabetes to normal (reducing the proportion of prediabetes and increasing the proportion to become normal) or reducing the risk of progression from prediabetes to Type 2-Diabetes Mellitus (T2DM) compared to placebo with standard healthy lifestyle intervention.

2. Secondary Objectives:

To investigate the level of Zinc and Chromium among the prediabetes, the safety of the ZCC supplementation, and the effect of a combination of Zinc, Chromium, Vitamin C, and Copper supplementation (ZCC supplementation) among prediabetic adults compared to the placebo supplementation on:

1. Lipid profile [Low-Density Lipoprotein (LDL), High-Density Lipoprotein (HDL), Triglyceride];

2. Hemoglobin A1c (HbA1c);

3. Dietary intake and physical activity

4. Body weight and composition (body weight, Body Mass Index (BMI), body fat).

3. Exploratory Objectives:

1. To determine cost effectiveness of intervention on prediabetic adults comparing two different intervention models

2. To determine the quality of life of prediabetes adults receiving a combination of zinc, chromium, vitamin C, and copper supplementation.

3. Level of hs-crp; TNF-alpha and Vitamin C will be assessed later if needed (optional)

Study Design:

This study is a double-blind, randomized, placebo-controlled trial in the community setting, with two arms of intervention involving a total of 670 people.

Study Duration:

This study is a two-year study with 1 year of intervention for each subject.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 670
• Est. completion date: March 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 35 Years to 65 Years

Eligibility

Inclusion Criteria:

• Adults aged between 35-65 years old;

• Being prediabetes as assessed by having fasting plasma glucose (FPG) level in the range of 100 mg/dL to 125 mg/dL; having 2-h values in the oral glucose tolerance (OGTT) level in the range of 140 mg/dL to 199 mg/dL;

• The study subjects will be recruited from household communities connected to any health care facilities such as primary health center, private clinics or private GP/specialist on the national health care system;

• The subjects are willing to sign informed consent;

• The subjects are willing to stay commitment during the study, at least 1 year;

• Having app-android mobile

Exclusion Criteria:

• Pregnancy or lactation women;

• Transgender on hormonal injection;

• Bariatric surgery;

• Consuming other pills supplementation containing zinc and/or chromium, copper, vitamin C in regular basis;

• History of Inflammatory Bowel Disease (IBD), psychiatric disorders, chronic diseases (e.g., HIV, Cushing syndrome, CKD, acromegaly, hyperthyroidism, etc.);

• Not healthy (current status of the severely malnourished, acute problem of any severe disease, history of impaired hepatic, renal failure, heart failure, cancer, other catastrophic diseases.

• Currently using weight loss medication;

• Consuming pharmacology agents that might interfere the intervention (such as metformin, methylprednisolone, methyltestosterone, diuretics, complementary medicines);

• Subjects who are unable to read and understand the statements of consent form

Related Conditions & MeSH terms

• Glucose Intolerance
• Nutrition
• PreDiabetes
• Prediabetic State

Intervention

Dietary Supplement:
• Zinc, Chromium, Vitamin C, and Copper Supplementation
Combination of mineral and vitamin supplementation that consist of Zinc, Chromium, Vitamin C, and Copper

Behavioral:
• Standard healthy lifestyle intervention
Standard healthy lifestyle intervention will follow the Guidelines on the Management and Prevention of Prediabetes by the Indonesian Ministry of Healthy and the Indonesian Diabetes Association.

Other:
• Placebo
Placebo with inactive ingredients

Locations

Country	Name	City	State
Indonesia	Human Nutrition Research Center, Indonesian Medical Education Research Institute (HNRC-IMERI) Faculty of Medicine, Universitas Indonesia	Jakarta Pusat	DKI Jakarta

Sponsors (2)

Lead Sponsor	Collaborator
Indonesia University	Blackmores Institute

Country where clinical trial is conducted

Indonesia, 

References & Publications (20)

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Aroda VR, Ratner R. Approach to the patient with prediabetes. J Clin Endocrinol Metab. 2008 Sep;93(9):3259-65. doi: 10.1210/jc.2008-1091. — View Citation

Ashor AW, Werner AD, Lara J, Willis ND, Mathers JC, Siervo M. Effects of vitamin C supplementation on glycaemic control: a systematic review and meta-analysis of randomised controlled trials. Eur J Clin Nutr. 2017 Dec;71(12):1371-1380. doi: 10.1038/ejcn.2017.24. Epub 2017 Mar 15. — View Citation

Bartlett HE, Eperjesi F. Nutritional supplementation for type 2 diabetes: a systematic review. Ophthalmic Physiol Opt. 2008 Nov;28(6):503-23. doi: 10.1111/j.1475-1313.2008.00595.x. — View 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. — View Citation

Dall TM, Yang W, Gillespie K, Mocarski M, Byrne E, Cintina I, Beronja K, Semilla AP, Iacobucci W, Hogan PF. The Economic Burden of Elevated Blood Glucose Levels in 2017: Diagnosed and Undiagnosed Diabetes, Gestational Diabetes Mellitus, and Prediabetes. Diabetes Care. 2019 Sep;42(9):1661-1668. doi: 10.2337/dc18-1226. Epub 2019 Apr 2. — View Citation

Eriksson J, Kohvakka A. Magnesium and ascorbic acid supplementation in diabetes mellitus. Ann Nutr Metab. 1995;39(4):217-23. doi: 10.1159/000177865. — View Citation

Guo CH, Wang CL. Effects of zinc supplementation on plasma copper/zinc ratios, oxidative stress, and immunological status in hemodialysis patients. Int J Med Sci. 2013;10(1):79-89. doi: 10.7150/ijms.5291. Epub 2012 Dec 22. — View Citation

Islam MR, Attia J, Ali L, McEvoy M, Selim S, Sibbritt D, Akhter A, Akter S, Peel R, Faruque O, Mona T, Lona H, Milton AH. Zinc supplementation for improving glucose handling in pre-diabetes: A double blind randomized placebo controlled pilot study. Diabetes Res Clin Pract. 2016 May;115:39-46. doi: 10.1016/j.diabres.2016.03.010. Epub 2016 Mar 19. — View Citation

Janghorbani M, Amini M. Normal fasting plasma glucose and risk of prediabetes and type 2 diabetes: the Isfahan Diabetes Prevention Study. Rev Diabet Stud. 2011 Winter;8(4):490-8. doi: 10.1900/RDS.2011.8.490. Epub 2012 Feb 10. — View Citation

Jayawardena R, Ranasinghe P, Byrne NM, Soares MJ, Katulanda P, Hills AP. Prevalence and trends of the diabetes epidemic in South Asia: a systematic review and meta-analysis. BMC Public Health. 2012 May 25;12:380. doi: 10.1186/1471-2458-12-380. — View Citation

Jayawardena R, Ranasinghe P, Galappatthy P, Malkanthi R, Constantine G, Katulanda P. Effects of zinc supplementation on diabetes mellitus: a systematic review and meta-analysis. Diabetol Metab Syndr. 2012 Apr 19;4(1):13. doi: 10.1186/1758-5996-4-13. — View Citation

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Khan MI, Siddique KU, Ashfaq F, Ali W, Reddy HD, Mishra A. Effect of high-dose zinc supplementation with oral hypoglycemic agents on glycemic control and inflammation in type-2 diabetic nephropathy patients. J Nat Sci Biol Med. 2013 Jul;4(2):336-40. doi: 10.4103/0976-9668.117002. — View Citation

Kim HN, Kim SH, Eun YM, Song SW. Effects of zinc, magnesium, and chromium supplementation on cardiometabolic risk in adults with metabolic syndrome: A double-blind, placebo-controlled randomised trial. J Trace Elem Med Biol. 2018 Jul;48:166-171. doi: 10.1016/j.jtemb.2018.03.022. Epub 2018 Mar 30. — View Citation

Paiva AN, Lima JG, Medeiros AC, Figueiredo HA, Andrade RL, Ururahy MA, Rezende AA, Brandao-Neto J, Almeida Md. Beneficial effects of oral chromium picolinate supplementation on glycemic control in patients with type 2 diabetes: A randomized clinical study. J Trace Elem Med Biol. 2015 Oct;32:66-72. doi: 10.1016/j.jtemb.2015.05.006. Epub 2015 May 28. — View Citation

Ranasinghe P, Wathurapatha WS, Galappatthy P, Katulanda P, Jayawardena R, Constantine GR. Zinc supplementation in prediabetes: A randomized double-blind placebo-controlled clinical trial. J Diabetes. 2018 May;10(5):386-397. doi: 10.1111/1753-0407.12621. Epub 2018 Jan 3. — View Citation

Sharma S, Agrawal RP, Choudhary M, Jain S, Goyal S, Agarwal V. Beneficial effect of chromium supplementation on glucose, HbA1C and lipid variables in individuals with newly onset type-2 diabetes. J Trace Elem Med Biol. 2011 Jul;25(3):149-53. doi: 10.1016/j.jtemb.2011.03.003. Epub 2011 May 12. — View Citation

Vistisen D, Kivimaki M, Perreault L, Hulman A, Witte DR, Brunner EJ, Tabak A, Jorgensen ME, Faerch K. Reversion from prediabetes to normoglycaemia and risk of cardiovascular disease and mortality: the Whitehall II cohort study. Diabetologia. 2019 Aug;62(8):1385-1390. doi: 10.1007/s00125-019-4895-0. Epub 2019 May 23. — View Citation

Will JC, Ford ES, Bowman BA. Serum vitamin C concentrations and diabetes: findings from the Third National Health and Nutrition Examination Survey, 1988-1994. Am J Clin Nutr. 1999 Jul;70(1):49-52. doi: 10.1093/ajcn/70.1.49. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cost Effectiveness Analysis of ZCC Supplement using Incremental cost-effectiveness ratio (ICER)	Analyzing the cost effectiveness of intervention on Prediabetic adults comparing 2 different intervention models using incremental cost-effectiveness ratio (ICER). ICER is the ratio of the change in costs of a therapeutic intervention (compared to the alternative, such as doing nothing or using the best available alternative treatment) to the change in effects of the intervention.	through study completion, an average of 1 year
Other	Change of Quality of Life Questionnaire (assessed by SF-36 questionnaire)	To determine the quality of life of prediabetes adults using standardized questionnaire on control and intervention group. he range of scores is between 15 to 105, with a higher score or number being indicative of a higher quality of life.	through study completion, an average of 1 year
Other	Change in High-sensitivity C-Reactive Protein (hs-CRP) level (optional)	To determine the difference of hs-CRP level in prediabetes adults with ZCC and placebo supplementation (optional).	through study completion, an average of 2 year
Other	Change in Tumor Necrosis Factor-alpha (TNF-alpha) Level (optional)	To determine the difference of TNF-alpha level in prediabetes adults with ZCC and placebo supplementation (optional).	through study completion, an average of 2 year
Other	Change in Vitamin C Level (optional)	To determine the difference of Vitamin C level in prediabetes adults with ZCC and placebo supplementation (optional).	through study completion, an average of 2 year
Primary	Change of Fasting Blood Glucose (FBG)	To investigate the effect of ZCC supplementation with standard healthy lifestyle intervention in improving Fasting Blood Glucose compared to placebo with standard healthy lifestyle intervention	Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
Primary	Change of Hemoglobin A1c (HbA1c)	To investigate the effect of ZCC supplementation with standard healthy lifestyle intervention in improving HbA1c compared to placebo with standard healthy lifestyle intervention	Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
Primary	Change of 2 hour Oral Glucose Tolerance Test (2-hour OGTT)	To investigate the effect of ZCC supplementation with standard healthy lifestyle intervention in improving 2 hour OGTT compared to placebo with standard healthy lifestyle intervention	Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
Primary	Change of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)	To investigate the effect of ZCC supplementation with standard healthy lifestyle intervention in improving HOMA-IR compared to placebo with standard healthy lifestyle intervention	Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
Primary	Delay Onset of Type 2 Diabetes Mellitus (T2DM) Progression	Total participants who develop T2DM during study intervention as assessed by blood glucose	Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
Primary	Change the Risk of T2DM Progression	Total participants whose blood glucose returned to normal during study intervention as assessed by blood glucose	Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
Secondary	Change in Lipid Profile (will be assessed by High Density Lipoprotein (HDL) in mg/dL, Low Density Lipoprotein (LDL) in mg/dL, Triglyceride (TG) in mg/dL, and total cholesterol in mg/dL))	To investigate the effect of ZCC supplementation among prediabetes adults on lipid profile (HDL, LDL, TG and total cholesterol)	Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
Secondary	Change in Body Weight (kilogram)	To investigate the effect of ZCC supplementation among prediabetes adults on changing in body weight.	Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
Secondary	Change in Body Mass Index (BMI) (weight and height will be combined to report the BMI in kg/m^2)	To investigate the effect of ZCC supplementation among prediabetes adults on changing in BMI.	Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
Secondary	Change in Percentage of Fat Mass (using Body Impedance Analysis)	To investigate the effect of ZCC supplementation among prediabetes adults on changing in fat mass using Body Impedance Analysis.	Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
Secondary	Change in Dietary intake	To determine the differences in changes of dietary intake after receiving 12 months of ZCC or placebo supplementation with standard healthy lifestyle intervention.	Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
Secondary	The Difference of Zinc Level among prediabetes adults	To determine the difference of Zinc level in prediabetes adults.	Baseline (at the beginning of study)
Secondary	The Difference of Chromium Level among prediabetes adults	To determine the difference of Chromium level in prediabetes adults.	Baseline (at the beginning of study)
Secondary	Change in Physical Activity (assessed by IPAQ Questionnaire)	To determine the difference of physical activity in prediabetes adults using standardized questionnaire on control and intervention group. Moderate intensity activities have been established as between 3 and 6 METS (metabolic equivalent of task). One MET is the amount of energy used while sitting quietly. Physical activities will be rated using METs to indicate their intensity. Vigorous-intensity activity activities have been established as >6 METs. The higher the MET scores mean a better physical activity.	Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
Secondary	The assessment on the Safety of the ZCC Supplementation for the respondents	To investigate the safety of the ZCC supplementation among prediabetes adults on the kidney function, liver function, and complete peripheral blood to assess whether the supplements have the specific effects for the respondents' organ function.	Baseline (at the beginning of study) and 12 months (end of the study)