Clinical trial NCT04511468: Zinc, Chromium, Vitamin C, and Copper Combination Supplement for Prediabetes Progression
Official title: A Combination of Zinc, Chromium, Vitamin C, and Copper Supplement for Prediabetes Progression: Randomized Controlled-Trial in Jakarta
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: PreDiabetes
Nutrition
Keywords: Zinc
Chromium
Copper
Vitamin C
Lead sponsor: Indonesia University
Sponsor class: OTHER
Collaborators: name: Blackmores Institute
First posted: 2020-08-13
Enrollment: 670
Sex: ALL
Minimum age (years): 35
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: There will be two arms of intervention:

Arm 1: A combination of Zinc, Chromium, Vitamin C, and Copper (ZCC supplement) with standard healthy lifestyle intervention.

Arm 2: A combination of placebo with standard healthy lifestyle intervention.
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change of Fasting Blood Glucose (FBG)
timeFrame: Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
measure: Change of Hemoglobin A1c (HbA1c)
timeFrame: Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
measure: Change of 2 hour Oral Glucose Tolerance Test (2-hour OGTT)
timeFrame: Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
measure: Change of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
timeFrame: Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
measure: Delay Onset of Type 2 Diabetes Mellitus (T2DM) Progression
timeFrame: Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
measure: Change the Risk of T2DM Progression
timeFrame: Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
Secondary outcomes:
measure: 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))
timeFrame: Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
measure: Change in Body Weight (kilogram)
timeFrame: Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
measure: Change in Body Mass Index (BMI) (weight and height will be combined to report the BMI in kg/m^2)
timeFrame: Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
measure: Change in Percentage of Fat Mass (using Body Impedance Analysis)
timeFrame: Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
measure: Change in Dietary intake
timeFrame: Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
measure: The Difference of Zinc Level among prediabetes adults
timeFrame: Baseline (at the beginning of study)
measure: The Difference of Chromium Level among prediabetes adults
timeFrame: Baseline (at the beginning of study)
measure: Change in Physical Activity (assessed by IPAQ Questionnaire)
timeFrame: Baseline (at the beginning of study), Intervention Period (3 and 6 months), and 12 months
measure: The assessment on the Safety of the ZCC Supplementation for the respondents
timeFrame: Baseline (at the beginning of study) and 12 months (end of the study)
Other outcomes:
measure: Cost Effectiveness Analysis of ZCC Supplement using Incremental cost-effectiveness ratio (ICER)
timeFrame: through study completion, an average of 1 year
measure: Change of Quality of Life Questionnaire (assessed by SF-36 questionnaire)
timeFrame: through study completion, an average of 1 year
measure: Change in High-sensitivity C-Reactive Protein (hs-CRP) level (optional)
timeFrame: through study completion, an average of 2 year
measure: Change in Tumor Necrosis Factor-alpha (TNF-alpha) Level (optional)
timeFrame: through study completion, an average of 2 year
measure: Change in Vitamin C Level (optional)
timeFrame: through study completion, an average of 2 year
Locations:
city: Jakarta Pusat
country: Indonesia
facility: Human Nutrition Research Center, Indonesian Medical Education Research Institute (HNRC-IMERI) Faculty of Medicine, Universitas Indonesia
state: DKI Jakarta
Study officials:
affiliation: HNRC-IMERI, Faculty of Medicine Universitas Indonesia
name: Rina Agustina, MD, MSc, PhD
role: PRINCIPAL_INVESTIGATOR
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