Insulin SensitivityNCT02686996
The Potential of Carnosine Supplementation in Reducing the Cardiometabolic Risk
A study testing carnosine in people with Insulin Sensitivity, run by Monash University at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Insulin Sensitivity
- What is being tested?
- carnosine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 1 siteAustralia
- Study dates
- 13 Feb 2017to 12 Jun 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Australia1 site, 1 recruiting
- Recruiting
Monash Centre for Health Research and Implementation
Melbourne, Victoria, 3168
Barbora de Courten, MD,PHD,MPH, +61 3 9594 7086, barbora.decourten@monash.edu
Barbora de Courten, MD,PHD,MPH
About this study
Official title: The Potential of Carnosine Supplementation in Reducing the Cardiometabolic Risk: a Double-blind, Placebo-controlled Trial
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).
Read more
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:
- Reducing diabetes risk (insulin sensitivity; secretory function and glucose tolerance)
- Improving cardiovascular risk factors (lipids; arterial (aortic) stiffness; central blood pressure (cBP); endothelial function).
- Decreasing the CLI, oxidative stress, AGEs, and ALEs, and increase detoxification of reactive carbonyl species (RCSs).
Read the 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.
- Conditions
- Insulin Sensitivity
- Being tested
- carnosine, Placebo
- Keywords
- carnosine, Insulin sensitivity, low grade inflammation, Oxidative stress, Advanced glycation, Type 2 diabetes, Cardiovascular disease
- Medical subject headings
- Insulin Resistance, Diabetes Mellitus, Type 2, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
carnosineDietary supplement
Carnosine capsules (2g) twice per day for 14 weeks
PlaceboOther
Placebo (methylcellulose) capsules for control group identical to intervention capsules and dose
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Active comparator | Each participant will be given a daily oral dose 2 g of carnosine (2 tablets twice daily) for 14 weeks Receives: Dietary Supplement: carnosine |
| Control | Placebo comparator | Each participant will be given a daily oral dose 2 g of identical placebo tablets ( 2 tablets twice daily) for 14 weeks Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in insulin sensitivity measured by euglycaemic glucose clamp
The clamp will be used to measure insulin sensitivity. The clamp is initiated by an intravenous bolus injection of insulin (9milliUnit/kg). Insulin is then constantly infused at a rate of 40 milliUnit.m-2.min-1 for 120 min into an arm vein, whilst glucose is variably infused to maintain euglycaemia. Plasma glucose values will be monitored every 5 minutes during the clamp and the variable infusion rate of glucose is adjusted to maintain blood glucose at a constant value of 5mmol/L.
Measured: From baseline to 14 weeks
Secondary outcomes (3)
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 plethysmo¬graphic signals of the finger arterial pulse wave. Finger plethysmographic probes are placed on each index finger; and after a 5 min equilib¬ration 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).
Measured: From baseline to 14 weeks
Change in Acute Insulin Secretory Response - Intravenous Glucose Tolerance Test
This will be measured in response to 25g intravenous glucose and calculated as the average incremental plasma insulin level from the third to the fifth minute after the glucose bolus.
Measured: From baseline to 14 weeks
Change in Resting 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.
Measured: From baseline to 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2016 (estimated)
- Study start13 Feb 2017
- Primary completion13 Feb 2020 (estimated)
- Study completion12 Jun 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Insulin SensitivityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 84 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Monash University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Barbora de Courten, Monash University
- Investigators
- Barbora de courten, MD,PHD,MPH, Principal investigator, Monash University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02686996
- Sponsor's protocol ID
- 16061A
- Status last verified
- Mar 2018
- First submitted
- 9 Feb 2016
- Last updated
- 22 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33986049
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Potential of Carnosine Supplementation in Reducing the Cardiometabolic Risk: a Double-blind, Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT02686996
- Acronym / sponsor ID
- 16061A
- Conditions
- Insulin Sensitivity
- Keywords
- carnosine, Insulin sensitivity, low grade inflammation, Oxidative stress, Advanced glycation, Type 2 diabetes, Cardiovascular disease
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 84 participants (estimated)
- Lead sponsor
- Monash UniversityUniversity, hospital or other
- Study start
- 13 Feb 2017 (actual)
- Primary completion
- 13 Feb 2020 (estimated)
- Study completion
- 12 Jun 2020 (estimated)
- First posted
- 22 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Reducing diabetes risk (insulin sensitivity; secretory function and glucose tolerance)
- Improving cardiovascular risk factors (lipids; arterial (aortic) stiffness; central blood pressure (cBP); endothelial function).
- 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Active comparator | Dietary Supplement: carnosineEach participant will be given a daily oral dose 2 g of carnosine (2 tablets twice daily) for 14 weeks |
| Control | Placebo comparator | Other: PlaceboEach participant will be given a daily oral dose 2 g of identical placebo tablets ( 2 tablets twice daily) for 14 weeks |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| carnosineCarnosine capsules (2g) twice per day for 14 weeks | Dietary supplement | Intervention |
| PlaceboPlacebo (methylcellulose) capsules for control group identical to intervention capsules and dose | Other | Control |
Primary outcome
Change in insulin sensitivity measured by euglycaemic glucose clamp
Time frame: From baseline to 14 weeks
The clamp will be used to measure insulin sensitivity. The clamp is initiated by an intravenous bolus injection of insulin (9milliUnit/kg). Insulin is then constantly infused at a rate of 40 milliUnit.m-2.min-1 for 120 min into an arm vein, whilst glucose is variably infused to maintain euglycaemia. Plasma glucose values will be monitored every 5 minutes during the clamp and the variable infusion rate of glucose is adjusted to maintain blood glucose at a constant value of 5mmol/L.
3 secondary outcomes
Change in markers of endothelial dysfunction
Time frame: From baseline to 14 weeks
Change in Acute Insulin Secretory Response - Intravenous Glucose Tolerance Test
Time frame: From baseline to 14 weeks
Change in Resting systolic and diastolic blood pressure
Time frame: From baseline to 14 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2018.
- Derived from this study: PubMed 33986049Menon 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.
- Individual participant dataSharing planned: No
Related trials for Insulin Sensitivity
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Improving Sleep Health and Circadian Timing to Support Cardiometabolic Health in Adolescents
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Not yet recruitingObservational study
Clinical Research Trial to Study Insulin Sensitivity Using Automated Glucose Clamp Technology
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Barbora de courten, MD,PHD,MPH principal investigator
Monash University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing carnosine in people with Insulin Sensitivity, run by Monash University at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Barbora de Courten, MD,PHD,MPH (+61 385722651, barbora.decourten@monash.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in insulin sensitivity measured by euglycaemic glucose clamp (time frame: From baseline to 14 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02686996, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2018.