Cardiovascular Risk Factors Clinical Trial
Official 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
NCT number | NCT02917928 |
Other study ID # | 16061AI |
Secondary ID | |
Status | Recruiting |
Phase | Phase 2 |
First received | |
Last updated | |
Start date | October 2016 |
Est. completion date | July 2023 |
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).
Status | Recruiting |
Enrollment | 40 |
Est. completion date | July 2023 |
Est. primary completion date | January 2023 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 70 Years |
Eligibility | 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 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 |
Country | Name | City | State |
---|---|---|---|
Australia | Monash Centre for Health Research and Implementation | Melbourne | Victoria |
Lead Sponsor | Collaborator |
---|---|
Monash University |
Australia,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Change in liver stiffness and fat | A non-invasive transient elastography (Fibroscan, EchoSens, Paris) will be used to assess liver fibrosis based on the measurement of liver fat and stiffness | baseline and 14 weeks | |
Other | Change in Serum and urine carnosine | This will be measured by ELISA for human carnosinase 1 (CN1) with a monoclonal antibody (clone ATLAS, Abcam plc) and peroxidase substrate . | baseline and 14 weeks | |
Other | Change in skeletal muscle fat and density | We will also measure the change in muscle and fat tissue density of participants' non-dominant leg using Quantitative Computed Tomography (pQCT). Participants will be seated in their non-dominant leg positioned inside the machine gantry. Muscle cross sectional area (mm2) and muscle density (mg/cm3) will be determined using the manufacturer's algorithms. | baseline and 14 weeks | |
Other | Change in body composition | body composition by dual energy x-ray absorptiometry (DEXA), which is a non-invasive assessment of soft tissue composition by region with a precision of 4-5%; central adiposity assessed in duplicate using a constant-tension tape for taking waist, and hip circumference. Bioimpedance measurement will be also collected for validation purposes. | baseline and 14 weeks | |
Primary | 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. | baseline and 14 weeks | |
Secondary | Change in HbA1c | Blood samples will be measured using High Performance Liquid Chromatography. | baseline and 14 weeks | |
Secondary | Change in lipid profile | Blood samples will be analysed using High Performance Liquid Chromatography | baseline and 14 weeks | |
Secondary | 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. | baseline and 14 weeks | |
Secondary | 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). | baseline and 14 weeks | |
Secondary | 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). | baseline and 14 weeks | |
Secondary | 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. | baseline and 14 weeks | |
Secondary | Change in interleukins | Interleukins will be measured by quantitative sandwich enzyme immunoassays (R & D Systems Inc, USA). | baseline and 14 weeks | |
Secondary | Change in tumour necrosis factor a | Tumour necrosis factor a (TNFa) will be measured by quantitative sandwich enzyme immunoassays (R & D Systems Inc, USA). | baseline and 14 weeks | |
Secondary | Change in macrophage migration inhibitory factor | Macrophage migration inhibitory factor will be measured by quantitative sandwich enzyme immunoassays (R & D Systems Inc, USA). | baseline and 14 weeks | |
Secondary | 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). | baseline and 14 weeks | |
Secondary | 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. | baseline and 14 weeks | |
Secondary | 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). | baseline and 14 weeks | |
Secondary | 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. | baseline and 14 weeks |
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