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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02917928




Registration number
NCT02917928
Ethics application status
Date submitted
19/09/2016
Date registered
28/09/2016
Date last updated
16/08/2018

Titles & IDs
Public title
The Potential of Carnosine Supplementation in Optimising Cardiometabolic Health
Scientific title
The Potential of Carnosine Supplementation in Optimising Cardiometabolic Health in Patients With Prediabetes and Type 2 Diabetes: a Randomsied, Double-blinded, Placebo-controlled Trial
Secondary ID [1] 0 0
16061AI
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Poor Glycemic Control 0 0
Cardiovascular Risk Factors 0 0
Cognitive Function 1, Social 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - carnosine
Treatment: Drugs - Placebo

Active Comparator: Intervention - Each participant will be given a daily oral dose 2 g of carnosine (4 tablets of 500mg each) for 14 weeks

Placebo Comparator: Control - Each participant will be given a daily oral dose 2 g of placebo (4 tablets of 500mg each) for 14 weeks


Other interventions: carnosine
Each participant will be given a daily oral dose 2 g of carnosine (4 tablets of 500mg each) for 14 weeks

Treatment: Drugs: Placebo
Each participant will be given a daily oral dose 2 g of placebo (4 tablets of 500mg each) for 14 weeks

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in Oral Glucose Tolerance Test - After a 10-12 h overnight fast, participants will ingest 75g of glucose over 2 mins. Blood samples will be drawn at 0, 30, 60, 90 and 120 min for plasma glucose and insulin concentrations. We will evaluate the area under the curve.
Timepoint [1] 0 0
baseline and 14 weeks
Secondary outcome [1] 0 0
Change in HbA1c - Blood samples will be measured using High Performance Liquid Chromatography.
Timepoint [1] 0 0
baseline and 14 weeks
Secondary outcome [2] 0 0
Change in lipid profile - Blood samples will be analysed using High Performance Liquid Chromatography
Timepoint [2] 0 0
baseline and 14 weeks
Secondary outcome [3] 0 0
Change in systolic and diastolic blood pressure - Resting systolic and diastolic blood pressure and pulse rate will be measured using an automated oscillometric measurement system (Dinamap, USA) after a 30 minute rest.
Timepoint [3] 0 0
baseline and 14 weeks
Secondary outcome [4] 0 0
Change in arterial stiffness and central blood pressure - Aortic (carotid-femoral) pulse wave velocity (aPWV) will be measured using the non-invasive Complior device (Alam Medical, French).
Timepoint [4] 0 0
baseline and 14 weeks
Secondary outcome [5] 0 0
Change in markers of endothelial dysfunction - This is done using non-invasive peripheral arterial tomography (PAT; endothelium-dependent digital pulse amplitude testing (EndoPAT), Itamar Medical Ltd, Israel), which records continuous plethysmographic signals of the finger arterial pulse wave. Finger plethysmographic probes are placed on each index finger; and after a 5 min equilibration period, a blood pressure cuff on the non-dominant arm is inflated to 60 mmHg above systolic for 5 min and then deflated to induce reactive hyperaemia. Measurements of post-occlusion changes (reactive hyperaemia PAT: RH-PAT) are continued for 10 min. Results are normalised to the non-occluded arm, compensating for potential systemic changes (RH-PAT ratio).
Timepoint [5] 0 0
baseline and 14 weeks
Secondary outcome [6] 0 0
Change in heart rate variability - The Zephyr Biomodule BH3 (Black Sensor, produced by Zephyr Technology) will be used to measure heart rate and heart rate variability for three consecutive days.
Timepoint [6] 0 0
baseline and 14 weeks
Secondary outcome [7] 0 0
Change in interleukins - Interleukins will be measured by quantitative sandwich enzyme immunoassays (R & D Systems Inc, USA).
Timepoint [7] 0 0
baseline and 14 weeks
Secondary outcome [8] 0 0
Change in tumour necrosis factor a - Tumour necrosis factor a (TNFa) will be measured by quantitative sandwich enzyme immunoassays (R & D Systems Inc, USA).
Timepoint [8] 0 0
baseline and 14 weeks
Secondary outcome [9] 0 0
Change in macrophage migration inhibitory factor - Macrophage migration inhibitory factor will be measured by quantitative sandwich enzyme immunoassays (R & D Systems Inc, USA).
Timepoint [9] 0 0
baseline and 14 weeks
Secondary outcome [10] 0 0
Change in plasma C- reactive protein - Plasma C- reactive protein (hsCRP) will be measured using high sensitivity assay (BN-II nephelometer; Dade Behring Diagnostics, NSW).
Timepoint [10] 0 0
baseline and 14 weeks
Secondary outcome [11] 0 0
Change in plasma and urinary advanced glycation end products - Measured by liquid chromatography-tandem mass spectrometry and ELISA tests. Circulating receptor for AGEs will be measured by ELISA. Protein modifications and the effect of carnosine supplementation will be determined by proteomic approaches.
Timepoint [11] 0 0
baseline and 14 weeks
Secondary outcome [12] 0 0
Change in plasma and urinary advanced lipoxidation end products - This will be determined by measuring the advanced oxidation protein products and by measuring the cysteinate form of albumin by mass spectrometry. Mercapturic acid adducts with the main reactive carbonyls species will also be quantitatively determined by liquid chromatography electrospray ionization mass spectrometry/mass spectrometry analysis (LC-MS/MS).
Timepoint [12] 0 0
baseline and 14 weeks
Secondary outcome [13] 0 0
Change in general cognitive function - Participants' cognitive function will be assessed using Cambridge Neuropsychological Test Automated Battery (CANTAB) battery for Prodromal Alzheimer's disease, Victoria Stroop test, Trail Making Test and Digit Symbol Substitution Test.
Timepoint [13] 0 0
baseline and 14 weeks

Eligibility
Key inclusion criteria
- Age >=18 or <=70 years

- Weight change < 5 kg in last 6 months

- HbA1c level <= 8%

- Patients with prediabetes (Impaired glucose tolerance and impaired fasting glycaemia)
or type 2 diabetes (diet controlled or on oral therapy)

- Patients will have to be on oral therapy for diabetes (without changes in treatment)
at least for 3 months.

- Patients will be advised not to change their pre-existing therapy for diabetes and
cardiovascular risk factors for the duration of the study if HbA1c is not above 8%

- No recent blood transfusion (3 months)

- No current intake of anti-inflammatory medications and supplements

- No significant kidney, cardiovascular, haematological, respiratory, gastrointestinal,
or central nervous system disease, as well as no psychiatric disorders, no active
cancer within the last five years; no presence of acute inflammation (by history,
physical or laboratory examination)

- Pregnant or lactating
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Age <18 or > 70 years

- HbA1c level of >= 8%

- Weight change > 5 kg in last 6 months

- Morbid obesity (body mass index >40 kg/m2)

- Current smoking habit and high alcohol use

- Patients on insulin

- Taking anti-inflammatory medications or supplements

- Recent blood transfusion history

- Kidney (estimated glomerular filtration rate < 30 ml/min), cardiovascular,
haematological, respiratory, gastrointestinal, or central nervous system disease, as
well as psychiatric disorder, active cancer within the last five years; presence of
acute inflammation (by history, physical or laboratory examination)

- Pregnancy or lactation

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Monash Centre for Health Research and Implementation - Melbourne
Recruitment postcode(s) [1] 0 0
3168 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Monash University
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The investigators hypothesise that carnosine supplementation will improve:

1. glycaemic control

2. cardiovascular risk factors

3. cognitive outcomes

in patients with prediabetes and type 2 diabetes, and this will be modulated by reduction in
chronic low grade inflammation, oxidative stress and circulating advanced glycation end
products levels.

3. Aims

To determine the potential of carnosine supplementation for 14 weeks to improve glycaemic
control in type 2 diabetes, reduce risk factors for cardiovascular disease and improve
cognitive function as well as identify metabolic pathways involved, specifically by:

1. Improving glycaemic control (HBA1c, fasting and 2 hour glucose and glucose area under
the curve after oral glucose tolerance test)

2. Reducing cardiovascular risk factors (lipids; arterial (aortic) stiffness; central blood
pressure (cBP); endothelial function).

3. Improve cognitive function (global cognitive score formed by a composite of 4 cognitive
tests)

4. Decrease the chronic low grade inflammation, oxidative stress, advanced glycation end
products, and advanced lipoxidation end products, and increase detoxification of
reactive carbonyl species (RCSs).
Trial website
https://clinicaltrials.gov/show/NCT02917928
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Barbora de courten, MD,PHD,MPH
Address 0 0
Monash University
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Barbora de Courten, MD,PHD,MPH
Address 0 0
Country 0 0
Phone 0 0
+61 385722651
Fax 0 0
Email 0 0
barbora.decourten@monash.edu
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02917928