Clinical trial NCT02686996: The Potential of Carnosine Supplementation in Reducing the Cardiometabolic Risk
Official title: The Potential of Carnosine Supplementation in Reducing the Cardiometabolic Risk: a Double-blind, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Insulin Sensitivity
Keywords: carnosine
Insulin sensitivity
low grade inflammation
Oxidative stress
Advanced glycation
Type 2 diabetes
Cardiovascular disease
Lead sponsor: Monash University
Sponsor class: OTHER
First posted: 2016-02-22
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim of this study is to determine whether carnosine supplementation in overweight/obese individuals can improve insulin secretion and/or insulin resistance by decreasing sub clinical inflammation.

The investigators hypothesise that carnosine supplementation will reduce type 2 diabetes and cardiovascular risk factors by lowering chronic low-grade inflammation (CLI), oxidative stress, advanced glycation end products (AGEs), and advanced lipoxidation end products (ALEs).

Aim :To determine the capacity of carnosine supplementation to decrease major risk factors for type 2 diabetes and cardiovascular disease and identify metabolic pathways involved, specifically by:

1. Reducing diabetes risk (insulin sensitivity; secretory function and glucose tolerance)
2. Improving cardiovascular risk factors (lipids; arterial (aortic) stiffness; central blood pressure (cBP); endothelial function).
3. Decreasing the CLI, oxidative stress, AGEs, and ALEs, and increase detoxification of reactive carbonyl species (RCSs).

Detailed description: Cardiovascular risk factors including type 2 diabetes underpin a major threat to the globe and result in a heavy health and financial burden across the healthcare system. Treating type 2 diabetes and cardiovascular disease is expensive and often unsatisfactory. Current medications bring unwanted side effects, and often merely delay rather than prevent type 2 diabetes complications and cardiovascular disease. As a further concern, the micro- and macrovascular complications of type 2 diabetes often start developing before actual diagnosis. Diabetes prevention and treatment through weight loss and exercise programs is a difficult and costly public health measure, leaving the tidal wave of type 2 diabetes to swell even more. An alternative is urgently needed: a low-cost safe approach, easy to implement at population level.

Could carnosine be that alternative? The evidence suggests carnosine has significant metabolic impact and presents such an alternative. A naturally occurring dipeptide, carnosine is already emerging as a human therapy in exercise physiology, heart failure, cataract prevention and treatment, neurology, and psychiatry. A promising further use may derive from its effect on cardiovascular risk factors. Metabolic research, though confined to animal studies, strongly suggests that carnosine supplementation aids the prevention and treatment of obesity, type 2 diabetes, and cardiovascular disease - by virtue of its anti-inflammatory, antioxidative, and anti-glycating effects. The investigators conducted the first pilot data in human and demonstrate relationships among carnosine, obesity, insulin resistance, and dyslipidemia. Put briefly, the pilot weighs strongly in favour of carnosine as a means of reducing cardiovascular risk in humans.

Too good to be true? Apart from its excellent side-effect profile, carnosine is inexpensive and seemingly safe (available as an over-the-counter food additive), making it prima facie ideal for population use. In this setting research is now urgently needed - to test the significant metabolic potential of carnosine to address a major health problem.

The investigators propose a comprehensive double-blind placebo-controlled human trial to investigate the effects of carnosine supplementation on cardiovascular risk factors. If the investigators demonstrate a role in reducing risk factors for type 2 diabetes and cardiovascular disease in overweight and obese non-diabetic humans, the public health implications will be revolutionary, offering the world a genuine low cost, accessible, intervention to curtail the advance of obesity, type 2 diabetes, and cardiovascular disease.

Eligibility criteria: Inclusion Criteria:

* Age \>18 or \<60 years,
* Weight change \< 5 kg in last 12 months
* BMI \>25kg/m2 but weight \<159kg due to DEXA scan restrictions
* Non-diabetic, no allergy, non-smoker, no high alcohol use
* No current intake of medications including vitamin supplements
* No kidney, cardiovascular, haematological, respiratory, gastrointestinal, endocrine 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)
* Not pregnant or lactating

Exclusion Criteria:

* Age \<18 or \> 60 years
* Weight change \> 5 kg in last 12 months
* Diabetes (diagnosed or oral glucose tolerance test (OGTT), allergy
* Current smoking habit, high alcohol use
* Current intake of medications including vitamin supplements
* Kidney, cardiovascular, haematological, respiratory, gastrointestinal, endocrine 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

Primary outcomes:
measure: Change in insulin sensitivity measured by euglycaemic glucose clamp
timeFrame: From baseline to 14 weeks
Secondary outcomes:
measure: Change in markers of endothelial dysfunction
timeFrame: From baseline to 14 weeks
measure: Change in Acute Insulin Secretory Response - Intravenous Glucose Tolerance Test
timeFrame: From baseline to 14 weeks
measure: Change in Resting systolic and diastolic blood pressure
timeFrame: From baseline to 14 weeks
Other outcomes:
measure: Change in Arterial waveform measurement
timeFrame: From baseline to 14 weeks
measure: Change in Oral Glucose Tolerance Test -OGTT
timeFrame: From baseline to 14 weeks
measure: Change in Measure of Adiposity (DEXA)
timeFrame: From baseline to 14 weeks
measure: Change in plasma and urinary AGEs
timeFrame: From baseline to 14 weeks
measure: Change in plasma and urinary ALEs
timeFrame: From baseline to 14 weeks
measure: Change in inflammatory markers
timeFrame: From baseline to 14 weeks
measure: Change in Carnosine concentrations in skeletal muscle
timeFrame: From baseline to 14 weeks
measure: Change in Serum and urine carnosine
timeFrame: From baseline to 14 weeks
measure: Change in Plasma carnosinase protein content
timeFrame: From baseline to 14 weeks
measure: Change in Other Tissue Analyses
timeFrame: From baseline to 14 weeks
Locations:
city: Melbourne
country: Australia
facility: Monash Centre for Health Research and Implementation
state: Victoria
Study officials:
affiliation: Monash University
name: Barbora de courten, MD,PHD,MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Menon K, Cameron JD, de Courten M, de Courten B. Use of carnosine in the prevention of cardiometabolic risk factors in overweight and obese individuals: study protocol for a randomised, double-blind placebo-controlled trial. BMJ Open. 2021 May 13;11(5):e043680. doi: 10.1136/bmjopen-2020-043680.