β-alanine Supplementation in Adults With Overweight/Obesity

Prediabetes Clinical Trial

— BASA-O  

Official title:

β-alanine Supplementation in Adults With Overweight or Obesity (BASA-O): A Randomised Controlled Feasibility Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05329610
• Other study ID #: 676
• Status: Completed
• Phase: N/A
• Start date: April 5, 2022
• Est. completion date: July 20, 2023

Study information

• Verified date: August 2023
• Source: Nottingham Trent University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will investigate the safety, feasibility, and efficacy of beta-alanine supplementation in adults with overweight or obesity. Beta-alanine is a widely used dietary supplement that can increase the amount of carnosine in skeletal muscle. Both carnosine and beta-alanine occur naturally in animal food products and previous research shows that supplementation with beta-alanine leads to an improvement in exercise performance; more recently, the present investigators have shown that increasing carnosine can also help to improve cardiometabolic health, detoxify skeletal muscle, and improve glucose (sugar) uptake into muscle cells. The investigators will recruit 30 participants (15 per arm) with overweight or obesity who meet the study criteria (this accounts for up to 20% attrition - a minimum of 12 participants per arm). Those who are eligible will be required to receive three short telephone calls and attend three laboratory sessions. Participants will be randomised to receive either beta-alanine or placebo (an inactive sugar pill) for the 3-month study period. To see whether beta-alanine supplementation is feasible in this population the investigators will measure recruitment, adherence (how well people can stick to the supplement regime), the number and nature of side effects, and blinding to the intervention. Markers of cardiac function, glycaemic control, and metabolic health will also be explored. All measurements will take place before and after a 3-month supplementation period. This will provide us with novel information of the role of beta-alanine and carnosine in cardiometabolic health; and will aid in the planning of a larger randomised controlled trial to assess the efficacy of beta-alanine supplementation as a therapeutic strategy.

Description:

Overweight and obesity are major public health problems. Recent estimates show that 64.3% of people in the UK are living with overweight or obesity; this is projected to increase to 71% by 2040, which equates to approx. 42.2 million people (Cancer Research UK, 2022). Overweight and obesity are characterised by excess amounts of adiposity and systemic, chronic, low-grade inflammation, which is associated with a range of metabolic disorders including dyslipidaemia, hypertension, and hyperglycaemia (Calder et al., 2011). This confers an increased risk of developing prediabetes, type-2 diabetes, and cardiovascular disease, as well as associated microvascular complications such as retinopathy, neuropathy, and nephropathy (Brannick et al., 2016). Lifestyle interventions can help delay or prevent the progression of overweight or obesity, thereby reducing morbidity (Lin et al., 2017; Wing et al., 2021). Such interventions, however, can be challenging to implement and a lack of long-term adherence can limit their effectiveness (Fappa et al., 2008). It is therefore important to develop low-cost, novel adjunct therapies to improve cardiometabolic health and help delay or prevent disease progression. The multifunctional dipeptide carnosine has emerged as a candidate for improving glycaemic control and cardiometabolic health. A recent meta-analysis showed that supplementation with carnosine, or its rate-limiting precursor β-alanine, reduces fasting glucose and HbA1c in humans and rodents. Work from our Research Group shows that treatment with carnosine decreases highly toxic lipid peroxidation products in skeletal muscle cells, leading to an increase in insulin-stimulated glucose uptake under glucolipotoxic conditions. A similar role occurs in vivo, where supplementation with β-alanine leads to greater formation of carnosine-adducts in post-exercise skeletal muscle samples. Given that skeletal muscle insulin resistance is a key component of prediabetes and type 2 diabetes, and reactive aldehydes can directly interfere with insulin signalling, carnosine may exert its therapeutic actions in skeletal muscle. There is also emerging evidence that carnosine, and other histidine-containing dipeptides (HCDs), play an important role in Ca2+ handling and excitation-contraction coupling in cardiac muscle, which may have implications for cardiovascular health. A limitation of existing studies is that the low carnosine dose used is likely to have only a modest effect on tissue carnosine content. Supplementation with β-alanine, however, can increase skeletal muscle carnosine content by 60-80% in 4-10 weeks, but it has not yet been trialled in adults with overweight or obesity. Please note: a change was made to the study eligibility criteria, which was approved by the UK Health Research Authority Research Ethics Committee on 01/09/2022.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: July 20, 2023
• Est. primary completion date: July 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Males and females aged 18 to 75 years
• Body Mass Index (BMI) =25 to <40 kg/m2
• Able to provide informed consent

Exclusion Criteria:

• Weight loss or gain =5 kg in the prior 6 months
• Current participation in another clinical research trial
• Substance abuse, presence of an eating disorder or purging behaviour
• Known mental health illness requiring active treatment
• Known cognitive impairment
• Inability to understand conversational English
• Presence of type-1 or type-2 diabetes mellitus
• Use of carnosine or ß-alanine supplements in the prior 6 months
• Current breastfeeding, pregnancy, or consideration of pregnancy
• Known comorbidities which may impact on study aims (e.g., cancer, heart failure, or chronic kidney disease) or measurement of study outcomes (e.g., sickle cell anaemia or previously known haemoglobinopathy)
• Use of weight loss or glucose lowering drugs (e.g., orlistat, thyroxine, metformin, insulin, glucagon-like-peptide-1 analogues), long-term corticosteroids, or other drugs which may impact on measurement of study outcomes

Related Conditions & MeSH terms

• Glucose Intolerance
• Hyperglycemia
• Obesity
• Overweight
• Overweight or Obesity
• Prediabetes
• Prediabetic State

Intervention

Dietary Supplement:
• Beta-alanine
Slow-release beta-alanine.
• Placebo
Taste and appearance-matched placebo (tapioca starch).

Locations

Country	Name	City	State
United Kingdom	Aston University	Birmingham	West Midlands
United Kingdom	Nottingham Trent University	Nottingham	Nottinghamshire

Sponsors (2)

Lead Sponsor	Collaborator
Nottingham Trent University	Aston University

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Body weight (kg)	Body weight will be measured with minimal clothing, using calibrated scales, and recorded to the nearest 0.1 kg.	Baseline and 3-months (endpoint)
Other	BMI (kg/m2)	Body mass index will be calculated from these measures, using the standard formula: [weight (kg) / height2 (m)].	Baseline and 3-months (endpoint)
Other	Waist circumference (cm)	Waist circumference will be taken as the circumference of the abdomen at its narrowest point, between the lower costal border and the top of the iliac crest.	Baseline and 3-months (endpoint)
Other	Hand grip strength (kg)	Hand grip strength will be measured using the standardised Southampton grip-strength protocol (Roberts et al., 2011).	Baseline and 3-months (endpoint)
Other	HbA1c (glycated haemoglobin)	Analyses will be performed using a Quo-Lab® HbA1c Analyzer (EKF Diagnostics, Germany).	Baseline and 3-months (endpoint)
Other	Fasting plasma glucose	Analyses will be performed using a Clinical Chemistry Analyser (ABX Pentra C400, Bergman Diagnostica, Horiba Medical, France).	Baseline and 3-months (endpoint)
Other	Fasting plasma insulin	Analyses will be performed using commercially available kits (e.g., enzyme-linked immunosorbent assays) and other relevant analytical methods.	Baseline and 3-months (endpoint)
Other	Plasma C-peptide	Analyses will be performed using commercially available kits (e.g., enzyme-linked immunosorbent assays) and other relevant analytical methods.	Baseline and 3-months (endpoint)
Other	Homeostatic model assessment of insulin sensitivity (HOMA2-S%)	HOMA2-S% will be used to estimate insulin sensitivity using the Oxford computer method (available from https://dtu.ox.ac.uk/homacalculator/) (Wallace et al., 2004).	Baseline and 3-months (endpoint)
Other	Homeostatic model assessment of beta-cell function (HOMA2-ß%)	HOMA2-ß% will be used to estimate ß-cell function using the Oxford computer method (available from https://dtu.ox.ac.uk/homacalculator/) (Wallace et al., 2004).	Baseline and 3-months (endpoint)
Other	Quantitative insulin sensitivity check index (QUICKI)	The QUICKI will be used as an additional measure of insulin sensitivity, using the standard formula: QUICKI = 1 / [log(fasting insulin) + log(fasting glucose)] (Katz et al., 2000).	Baseline and 3-months (endpoint)
Other	Plasma fructosamine	Analyses will be performed using a Clinical Chemistry Analyser (ABX Pentra C400, Bergman Diagnostica, Horiba Medical, France).	Baseline and 3-months (endpoint)
Other	Plasma C-reactive protein	Analyses will be performed using a Clinical Chemistry Analyser (ABX Pentra C400, Bergman Diagnostica, Horiba Medical, France).	Baseline and 3-months (endpoint)
Other	Plasma lipids and profile	High density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol (TC), triglycerides, LDL:HDL, and TC:HDL. Analyses will be performed using a Clinical Chemistry Analyser (ABX Pentra C400, Bergman Diagnostica, Horiba Medical, France).	Baseline and 3-months (endpoint)
Other	Plasma apolipoprotein A-1	Analyses will be performed using a Clinical Chemistry Analyser (ABX Pentra C400, Bergman Diagnostica, Horiba Medical, France), commercially available kits (e.g., enzyme-linked immunosorbent assays) and other relevant analytical methods.	Baseline and 3-months (endpoint)
Other	Plasma apolipoprotein B	Analyses will be performed using a Clinical Chemistry Analyser (ABX Pentra C400, Bergman Diagnostica, Horiba Medical, France), commercially available kits (e.g., enzyme-linked immunosorbent assays) and other relevant analytical methods.	Baseline and 3-months (endpoint)
Other	Plasma and urine markers of carnosine and carnosinase metabolism	Blood and urine analyses will be performed using commercially available kits (e.g., enzyme-linked immunosorbent assays) and other relevant analytical methods.	Baseline and 3-months (endpoint)
Other	Plasma and urine markers of oxidative stress, glycation, and lipid peroxidation	Blood and urine analyses will be performed using commercially available kits (e.g., enzyme-linked immunosorbent assays) and other relevant analytical methods.	Baseline and 3-months (endpoint)
Other	Liver function: alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma-glutamyl transferase, lactate dehydrogenase, creatine kinase (U/L).	Blood analyses will be performed using a Clinical Chemistry Analyser (ABX Pentra C400, Bergman Diagnostica, Horiba Medical, France); commercially available kits (e.g., enzyme-linked immunosorbent assays); and other relevant analytical methods.	Baseline and 3-months (endpoint)
Other	Liver function: albumin and total protein (g/L)	Blood analyses will be performed using a Clinical Chemistry Analyser (ABX Pentra C400, Bergman Diagnostica, Horiba Medical, France); commercially available kits (e.g., enzyme-linked immunosorbent assays); and other relevant analytical methods.	Baseline and 3-months (endpoint)
Other	Kidney and liver function: serum creatinine and total bilirubin (µmol/L)	Blood analyses will be performed using a Clinical Chemistry Analyser (ABX Pentra C400, Bergman Diagnostica, Horiba Medical, France); commercially available kits (e.g., enzyme-linked immunosorbent assays); and other relevant analytical methods.	Baseline and 3-months (endpoint)
Other	Kidney function: urea (mmol/L)	Blood analyses will be performed using a Clinical Chemistry Analyser (ABX Pentra C400, Bergman Diagnostica, Horiba Medical, France); commercially available kits (e.g., enzyme-linked immunosorbent assays); and other relevant analytical methods.	Baseline and 3-months (endpoint)
Other	Estimated glomerular filtration rate (eGFR) (mL/min/1.73m2).	Calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, which uses serum creatinine (µmol/L), age, sex, and race.	Baseline and 3-months (endpoint)
Other	Urinary albumin:creatinine ratio (mg/mmol)	Calculated from measurements of urine albumin (mg/L) and urine creatinine (µmol/L).	Baseline and 3-months (endpoint)
Other	N-terminal pro-brain natriuretic peptide (NT-proBNP)	Analyses will be performed using commercially available kits (e.g., enzyme-linked immunosorbent assays) and other relevant analytical methods.	Baseline and 3-months (endpoint)
Other	Diastolic, systolic, and meal arterial blood pressures (mmHg)	Non-invasive continuous haemodynamic measurements will be recorded using the CNAP Monitor (CNSystems, Graz; Austria), which uses fingertip plethysmography to accurately measure the beat-to-beat blood pressure wave form; or SBP/DBP will be measured using an automated sphygmomanometer.	Baseline and 3-months (endpoint)
Other	Cardiac output (L/min)	Calculated from measurements of stroke volume (mL) and heart rate (bpm), using the CNAP Monitor (CNSystems, Graz; Austria); and/or from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer.	Baseline and 3-months (endpoint)
Other	Stroke volume index (mL/m2)	Calculated using body index from measurements using the CNAP Monitor (CNSystems, Graz; Austria); and/or from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer.	Baseline and 3-months (endpoint)
Other	Cardiac index (L/min/m2)	Calculated using body index from measurements using the CNAP Monitor (CNSystems, Graz; Austria); and/or from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer.	Baseline and 3-months (endpoint)
Other	Systemic vascular resistance (SVR) (dyne*s/cm5)	Calculated using cardiac output (L/min) and mean arterial pressure (mmHg).	Baseline and 3-months (endpoint)
Other	Systemic vascular resistance (SVR) (dyne*s*m2/cm5)	Calculated using cardiac output (L/min), mean arterial pressure (mmHg), and body index.	Baseline and 3-months (endpoint)
Other	Isovolumetric contraction and relaxation times (IVCT/IVRT) (ms)	Calculated from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer.	Baseline and 3-months (endpoint)
Other	Left ventricular ejection fraction and systolic function (LVEF/LVSF) (%)	Calculated from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer.	Baseline and 3-months (endpoint)
Other	End systolic and diastolic volumes (mL)	Calculated from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer.	Baseline and 3-months (endpoint)
Other	Left ventricle systolic and diastolic diameters (mm)	Calculated from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer.	Baseline and 3-months (endpoint)
Other	Myocardial performance index (MPI) (also known as Tei Index; TI)	Calculated from the sum of isovolumic contraction time (ICT) and isovolumic relaxation time (IRT) divided by ejection time (ET).	Baseline and 3-months (endpoint)
Other	Ejection time (ms)	Calculated from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer.	Baseline and 3-months (endpoint)
Other	Aortic blood flow and A-Vmax (cm/s)	Calculated from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer.	Baseline and 3-months (endpoint)
Other	E wave deceleration time (DT) (ms)	Calculated from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer.	Baseline and 3-months (endpoint)
Other	E wave (m/s)	Calculated from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer.	Baseline and 3-months (endpoint)
Other	A wave (m/s)	Calculated from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer.	Baseline and 3-months (endpoint)
Other	E/A ratio	Calculated from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer.	Baseline and 3-months (endpoint)
Other	E'	Calculated from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer.	Baseline and 3-months (endpoint)
Other	e/e'	Calculated from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer.	Baseline and 3-months (endpoint)
Other	Left and right ventricular dimensions (mm)	Calculated from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer.	Baseline and 3-months (endpoint)
Other	Left and right ventricular areas and atrial area (cm/2)	Calculated from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer.	Baseline and 3-months (endpoint)
Other	Left and right ventricular outflow tract views (LVOT/RVOT) (mm or cm)	Calculated from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer.	Baseline and 3-months (endpoint)
Other	Left and right diastolic function (cm/s)	Calculated from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer.	Baseline and 3-months (endpoint)
Other	Right ventricular fractional area change (RVFAC) (%)	Calculated from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer.	Baseline and 3-months (endpoint)
Other	Left and right ventricle tissue doppler imaging (LVTDI/RVTDI) (cm/s)	Calculated from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer.	Baseline and 3-months (endpoint)
Other	Left ventricle longitudinal, circumferential, and radial strain	Calculated from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer. Reported as % or % per second.	Baseline and 3-months (endpoint)
Other	Left ventricle twist and untwist mechanics	Calculated from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer. Reported as degrees or degrees per second.	Baseline and 3-months (endpoint)
Other	Right ventricle longitudinal strain	Calculated from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer. Reported as % or % per second.	Baseline and 3-months (endpoint)
Other	Tricuspid annual plane systolic excursion (TAPSE) (mm)	Calculated from resting transthoracic echocardiographic (TTE) measurements using a portable ultrasound system (Siemens, USA) and a 4 mHz cardiac transducer.	Baseline and 3-months (endpoint)
Other	Fractional shortening (%)	The reduction of the length of the end-diastolic diameter that occurs by the end of systole, calculated as: (((LVEDD - LVESD) / LVEDD)) * 100).	Baseline and 3-months (endpoint)
Primary	Adherence to the intervention	Probability that a randomised participant receives the assigned intervention.	3-months (endpoint)
Secondary	Recruitment	Probability an eligible participant consents and is randomised.	Baseline
Secondary	Attrition rate	Probability that a randomised participant is evaluated for baseline and follow-up.	3-months (endpoint)
Secondary	Side effects	Data collected using the GASE questionnaire.	Baseline and 3-months (endpoint)
Secondary	Blinding to the intervention	Assessed using the -1, 0, +1 scale (Bang et al., 2004).	3-months (endpoint)