ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12615000559516

Ethics application status

Approved

Date submitted

25/05/2015

Date registered

29/05/2015

Date last updated

8/06/2018

Type of registration

Prospectively registered

Titles & IDs

Public title

Nutritional Supplements for prevention of type 2 diabetes

Scientific title

Combined effects of Curcumin and Omega 3 fatty acids on plasma glucose, lipid levels and inflammation bio-markers in the individuals with pre-diabetes.

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

COP-D trial

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Pre-diabetes

Condition category

Condition code

Metabolic and Endocrine

Diabetes

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Study participants will be randomly allocated to these treatment arms for 3 months
Arm 1 : Placebo: 4 capsules/day (2 each for curcumin and fish oil placebos)
Arm 2 : Curcumin (2 Tab @500 mg each) providing 180 mg curcumin plus 2 placebo capsules/day
Arm 3: n-3PUFA (2 cap @1000mg each) providing 1.2g EPA/DHA plus 2 placebo capsules/day
Arm 4: Curcumin (2 Tab @500 mg each providing a total of 180 mg curcumin) and n-3PUFA (2 cap @1000mg each providing a total of 1.2g EPA/DHA) per day

To monitor adherence to intervention,
1. Capsule intake by participants will be measured on 6th and 12th week
2. Compliance to the omega 3 fatty acids will be monitored by measuring participant's erythrocyte fatty acid content
3. Adherence to curcumin will be monitored by measuring curucmin content in the participant blood sample by using HPLC method.

Intervention code [1]

Treatment: Other

Intervention code [2]

Prevention

Comparator / control treatment

Fish oil placebo - Corn oil
Curcumin Placebo - Microcrystalline cellulose and dicalcium phosphate anhydrous

Control group

Placebo

Outcomes

Primary outcome [1]

HbA1c levels in blood sample

Analysed by Hunter New England Area Pathology Services (HNEPS)

Timepoint [1]

At baseline and post - intervention (12th week)

Secondary outcome [1]

Fasting plasma glucose levels
Analysed by Hunter New England Area Pathology Services (HNEPS)

Timepoint [1]

At base line (0 week) and post - intervention (12th week)

Secondary outcome [2]

HOMA-IR
Analysed by Hunter New England Area Pathology Services (HNEPS)

Timepoint [2]

At base line (0 week) and post - intervention (12th week)

Secondary outcome [3]

Fasting plasma insulin levels
Analysed by Hunter New England Area Pathology Services (HNEPS)

Timepoint [3]

At base line (0 week) and post - intervention (12th week)

Secondary outcome [4]

Fasting Total cholesterol in blood sample
Analysed by Hunter New England Area Pathology Services (HNEPS)

Timepoint [4]

At base line (0 week) and post - intervention (12th week)

Secondary outcome [5]

Fasting HDL cholesterol in blood sample
Analysed by Hunter New England Area Pathology Services (HNEPS)

Timepoint [5]

At base line (0 week) and post - intervention (12th week)

Secondary outcome [6]

Fasting LDL cholesterol in blood sample
Analysed by Hunter New England Area Pathology Services (HNEPS)

Timepoint [6]

At base line (0 week) and post - intervention (12th week)

Secondary outcome [7]

Adiponectin (ELISA method)

Timepoint [7]

At base line (0 week) and post - intervention (12th week)

Secondary outcome [8]

Leptin (ELISA method)

Timepoint [8]

At base line (0 week) and post - intervention (12th week)

Secondary outcome [9]

C-Reactive protein in blood sample
Analysed by Hunter New England Area Pathology Services (HNEPS)

Timepoint [9]

At base line (0 week) and post-intervention (12th week)

Secondary outcome [10]

Interleukin - 6 (ELISA method )

Timepoint [10]

At base line (O week) and post intervention (12 week)

Secondary outcome [11]

Insulin Amyloid Polypeptide (IAPP) in the blood samples was analysed using ELISA technique.

Timepoint [11]

At baseline (0 week) and post-intervention(12 week)

Secondary outcome [12]

Glycogen synthase kinase - 3 (GSK-3) in the blood samples was analysed using ELISA technique.

Timepoint [12]

At baseline (0 week) and post-intervention (12 week)

Eligibility

Key inclusion criteria

Age – 30-70; gender – both males and females
No participation in any clinical trial for at least 3 months
An HbA1c of 5.7% - 6.4%
Impaired Glucose Tolerance (IGT):
2-hour OGTT plasma glucose greater than or equal to 7.8 mmol/ Land <11.1 mmol/L
Impaired fasting glucose (IFG):
Fasting plasma venous glucose measurement 6.1–6.9 mmol/L
12 or more score or High risk individuals in AUSDRISK assessment tool
BMI between 25-45

Minimum age

30 Years

Maximum age

70 Years

Sex

Both males and females

Can healthy volunteers participate?

No

Key exclusion criteria

Pregnancy or lactation
Established type 2 diabetes
Allergic to sea foods
People with gall bladder problems
People currently on medication with erythropoietin
People with anaemia
People with pace maker implants
Currently on medication with Aspirin and Warfarin
History of severe neurological diseases or seizures
History of new investigational drug three months prior to this trial
Consuming more than 2 serve of oily fish per week
Taking regular dietary supplements known to influence blood glucose level
People taking regular vitamin C supplements
Unwilling to fast for 10hr before obtaining blood samplePeople currently on medication with clopidogrel, ibuprofen, naproxen, dalteparin, enoxaparin and heparin,

Study design

Purpose of the study

Prevention

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Participants will be recruited from the general public through media advertising, advertisements placed on noticeboards at the University of Newcastle and pharmacies and distributed via departmental email lists. Participants will also be recruited from the Hunter Medical Research Institute (HMRI) Volunteer Register. Participants will complete a health questionnaire and AUSDRISK tool to ensure that inclusion criteria are met. Randomization of participants to one of the group diets will be performed by one of the researchers in the research group. Allocation is not concealed

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Randomization of participants to one of the group diets will be performed by randomization table created by computer software.

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Factorial

Other design features

Phase

Phase 3

Type of endpoint/s

Efficacy

Statistical methods / analysis

With a mean deviation of 0.5 units in HbA1c, a sample size of seventeen participants in each treatment group will give 80% power to detect a 0.5 units drop in HbA1c at type 1 error (alpha)= 0.05. To allow for dropouts we will recruit 4x20 = 80 participants according to the inclusion criteria. Data obtained from all participants will be analysed according to the intention to treat theory. Normality of baseline data will be examined using histograms with a normal distribution curve overlayed and Shapiro Wilk’s test. Based on the distribution of data, the outcome measures will be analysed using ANOVA (normal distribution) or wilcoxon signed rank test (non-parametric data). Two-way ANOVA with post hoc comparisons will be used to determine the effect of intervention on different variables and also to determine synergistic or complimentary effects of two interventions (curcumin and LCn-3PUFA). ANCOVA will be used to assess the effects of confounding factors on treatment that include age, gender, BMI physical activity levels and dietary intake. Significance will be set at P-value <0.05. Statistical analysis will be performed using GraphPad Prism version 6 and IBM SPSS 22 software.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

30/06/2015

Actual

27/07/2015

Date of last participant enrolment

Anticipated

31/07/2017

Actual

25/07/2017

Date of last data collection

Anticipated

31/10/2017

Actual

23/10/2017

Sample size

Target

80

Accrual to date

Final

72

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment postcode(s) [1]

2308 - Newcastle University

Recruitment postcode(s) [2]

2310 - Hunter Region

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

Professor Manohar Garg

Address [1]

305C Medical Science Building
University of Newcastle
Callaghan, NSW 2308
AUSTRALIA

Country [1]

Australia

Primary sponsor type

University

Name

University of Newcastle

Address

University of Newcastle
Callaghan NSW 2308
Australia

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Human Research Ethics Committee (HREC) - University of Newcastle

Ethics committee address [1]

University of Newcastle
Callaghan, NSW 2308
AUSTRALIA

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

08/05/2015

Ethics approval number [1]

H-2014-0385

Ethics committee name [2]

Hunter New England Human Research Ethics Committe

Ethics committee address [2]

Hunter New England Research Support & Development Office
Locked Bag No 1
New Lambton NSW 2305

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

04/02/2016

Approval date [2]

05/04/2016

Ethics approval number [2]

16/03/16/3.02

Summary

Brief summary

Diabetes is a chronic non-communicable and slowly progressing metabolic disease often involving multiple pathological mechanisms. Multiple mechanisms underlie the pathogenesis of diabetes including subclinical inflammation, glucotoxicity and  lipotoxicity. Elevated levels of inflammation, particularly in the adipose tissue, is believed to be the primary trigger preceded by all of the above mentioned pathological mechanisms. Recent scientific literature established a strong link between inflammation and diabetes highlighting the role of inflammation as a primary pathological trigger for development of diabetes and its complications. Current therapies in the diabetes are unidimensional, targeted only to ameliorate the hyperglycaemic conditions. To date little or no attention has been paid to design pharmaceutical strategies to delay or modulate inflammatory pathways involved in reducing insulin secretion and/or action. Moreover current anti-diabetic medications have persistent side effects, such as body weight gain and hypoglycaemia in patients on sulphonylureas and insulin; gastrointestinal problems with metformin and acarbose; weight gain and bone fractures with thiazolidinediones; genital or urinary tract infections predominantly in females with sodium glucose co-transporter inhibitors.  In the light of increasing prevalence and health costs associated with diabetes and its complications, there is a necessity for development of easy to comply strategies to modulate multiple metabolic targets with excellent long-term safety profile. In search of these agents, some bioactive compounds (nutraceuticals) aiming at prevention of diabetes through anti-inflammatory mechanisms have shown promising results. Extensive research has been carried out on anti-inflammatory and anti-hyperglycaemic potential of curcumin. Also the long chain n-3PUFA have been shown to possess lipid-lowering and anti-inflammatory properties by modulating multiple metabolic targets. We propose to evaluate the complimentary and/or synergistic effects of curcumin and/or n-3PUFA on pro-inflammatory mediators and insulin sensitivity in people with pre-diabetes. This is a 2x2 factorial, randomized, double blind, placebo controlled study. Eligible participants will be asked to consume 4 caps daily; placebo, curucmin plus placebo, omega 3 fatty acids plus placebo, curucmin and omega 3 fatty acids combination, for 12 weeks. Participants will be donating blood on the first day and post intervention along with information on 3 day food consumption, physical activity and other medications.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Manohar Garg

Address

Nutraceuticals Research Group
305C Medical Science Building
University of Newcastle
Callaghan, NSW 2308
AUSTRALIA

Country

Australia

Phone

+61 2 4921 5647

Fax

+61 2 4921 2028

Email

manohar.garg@newcastle.edu.au

Contact person for public queries

Name

Rohith N Thota

Address

Nutraceuticals Research Group
MS3-05 Medical Science Building
University of Newcastle
Callaghan, NSW 2308

Country

Australia

Phone

+61-2-4921 5636

Fax

+61 2 4921 2028

Email

rohithnagendra.thota@uon.edu.au

Contact person for scientific queries

Name

Manohar Garg

Address

Nutraceuticals Research Group
305C Medical Science Building
University of Newcastle
Callaghan, NSW 2308
AUSTRALIA

Country

Australia

Phone

+61 2 4921 5647

Fax

Email

manohar.garg@newcastle.edu.au

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Curcumin and long-chain Omega-3 polyunsaturated fatty acids for Prevention of type 2 Diabetes (COP-D): Study protocol for a randomised controlled trial.	2016	https://dx.doi.org/10.1186/s13063-016-1702-9
Embase	Curcumin and/or omega-3 polyunsaturated fatty acids supplementation reduces insulin resistance and blood lipids in individuals with high risk of type 2 diabetes: A randomised controlled trial.	2019	https://dx.doi.org/10.1186/s12944-019-0967-x
Embase	Dietary supplementation with curcumin reduce circulating levels of glycogen synthase kinase-3B and islet amyloid polypeptide in adults with high risk of type 2 diabetes and Alzheimer's disease.	2020	https://dx.doi.org/10.3390/nu12041032
Embase	Efficacy and Safety of Curcumin Supplement on Improvement of Insulin Resistance in People with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.	2021	https://dx.doi.org/10.1155/2021/4471944
Embase	Nrf2: Therapeutic target of islet function protection in diabetes and islet transplantation.	2023	https://dx.doi.org/10.1016/j.biopha.2023.115463

N.B. These documents automatically identified may not have been verified by the study sponsor.