Clinical trial NCT05329610: β-alanine Supplementation in Adults With Overweight/Obesity
Official title: β-alanine Supplementation in Adults With Overweight or Obesity (BASA-O): A Randomised Controlled Feasibility Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prediabetes
Hyperglycemia
Overweight or Obesity
Keywords: Prediabetes
Hyperglycemia
Carnosine
Overweight
Obesity
Lead sponsor: Nottingham Trent University
Sponsor class: OTHER
Collaborators: name: Aston University
First posted: 2022-04-15
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A double-blinded, randomised, placebo-controlled, parallel group, feasibility trial. The allocation ratio of treatment to placebo will be 1:1.
Primary purpose: OTHER

Brief 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.

Detailed 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.

Eligibility criteria: 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 β-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

Primary outcomes:
measure: Adherence to the intervention
timeFrame: 3-months (endpoint)
Secondary outcomes:
measure: Recruitment
timeFrame: Baseline
measure: Attrition rate
timeFrame: 3-months (endpoint)
measure: Side effects
timeFrame: Baseline and 3-months (endpoint)
measure: Blinding to the intervention
timeFrame: 3-months (endpoint)
Other outcomes:
measure: Body weight (kg)
timeFrame: Baseline and 3-months (endpoint)
measure: BMI (kg/m2)
timeFrame: Baseline and 3-months (endpoint)
measure: Waist circumference (cm)
timeFrame: Baseline and 3-months (endpoint)
measure: Hand grip strength (kg)
timeFrame: Baseline and 3-months (endpoint)
measure: HbA1c (glycated haemoglobin)
timeFrame: Baseline and 3-months (endpoint)
measure: Fasting plasma glucose
timeFrame: Baseline and 3-months (endpoint)
measure: Fasting plasma insulin
timeFrame: Baseline and 3-months (endpoint)
measure: Plasma C-peptide
timeFrame: Baseline and 3-months (endpoint)
measure: Homeostatic model assessment of insulin sensitivity (HOMA2-S%)
timeFrame: Baseline and 3-months (endpoint)
measure: Homeostatic model assessment of beta-cell function (HOMA2-β%)
timeFrame: Baseline and 3-months (endpoint)
measure: Quantitative insulin sensitivity check index (QUICKI)
timeFrame: Baseline and 3-months (endpoint)
measure: Plasma fructosamine
timeFrame: Baseline and 3-months (endpoint)
measure: Plasma C-reactive protein
timeFrame: Baseline and 3-months (endpoint)
measure: Plasma lipids and profile
timeFrame: Baseline and 3-months (endpoint)
measure: Plasma apolipoprotein A-1
timeFrame: Baseline and 3-months (endpoint)
measure: Plasma apolipoprotein B
timeFrame: Baseline and 3-months (endpoint)
measure: Plasma and urine markers of carnosine and carnosinase metabolism
timeFrame: Baseline and 3-months (endpoint)
measure: Plasma and urine markers of oxidative stress, glycation, and lipid peroxidation
timeFrame: Baseline and 3-months (endpoint)
measure: Liver function: alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma-glutamyl transferase, lactate dehydrogenase, creatine kinase (U/L).
timeFrame: Baseline and 3-months (endpoint)
measure: Liver function: albumin and total protein (g/L)
timeFrame: Baseline and 3-months (endpoint)
measure: Kidney and liver function: serum creatinine and total bilirubin (µmol/L)
timeFrame: Baseline and 3-months (endpoint)
measure: Kidney function: urea (mmol/L)
timeFrame: Baseline and 3-months (endpoint)
measure: Estimated glomerular filtration rate (eGFR) (mL/min/1.73m2).
timeFrame: Baseline and 3-months (endpoint)
measure: Urinary albumin:creatinine ratio (mg/mmol)
timeFrame: Baseline and 3-months (endpoint)
measure: N-terminal pro-brain natriuretic peptide (NT-proBNP)
timeFrame: Baseline and 3-months (endpoint)
measure: Diastolic, systolic, and meal arterial blood pressures (mmHg)
timeFrame: Baseline and 3-months (endpoint)
measure: Cardiac output (L/min)
timeFrame: Baseline and 3-months (endpoint)
measure: Stroke volume index (mL/m2)
timeFrame: Baseline and 3-months (endpoint)
measure: Cardiac index (L/min/m2)
timeFrame: Baseline and 3-months (endpoint)
measure: Systemic vascular resistance (SVR) (dyne*s/cm5)
timeFrame: Baseline and 3-months (endpoint)
measure: Systemic vascular resistance (SVR) (dyne*s*m2/cm5)
timeFrame: Baseline and 3-months (endpoint)
measure: Isovolumetric contraction and relaxation times (IVCT/IVRT) (ms)
timeFrame: Baseline and 3-months (endpoint)
measure: Left ventricular ejection fraction and systolic function (LVEF/LVSF) (%)
timeFrame: Baseline and 3-months (endpoint)
measure: End systolic and diastolic volumes (mL)
timeFrame: Baseline and 3-months (endpoint)
measure: Left ventricle systolic and diastolic diameters (mm)
timeFrame: Baseline and 3-months (endpoint)
measure: Myocardial performance index (MPI) (also known as Tei Index; TI)
timeFrame: Baseline and 3-months (endpoint)
measure: Ejection time (ms)
timeFrame: Baseline and 3-months (endpoint)
measure: Aortic blood flow and A-Vmax (cm/s)
timeFrame: Baseline and 3-months (endpoint)
measure: E wave deceleration time (DT) (ms)
timeFrame: Baseline and 3-months (endpoint)
measure: E wave (m/s)
timeFrame: Baseline and 3-months (endpoint)
measure: A wave (m/s)
timeFrame: Baseline and 3-months (endpoint)
measure: E/A ratio
timeFrame: Baseline and 3-months (endpoint)
measure: E'
timeFrame: Baseline and 3-months (endpoint)
measure: e/e'
timeFrame: Baseline and 3-months (endpoint)
measure: Left and right ventricular dimensions (mm)
timeFrame: Baseline and 3-months (endpoint)
measure: Left and right ventricular areas and atrial area (cm/2)
timeFrame: Baseline and 3-months (endpoint)
measure: Left and right ventricular outflow tract views (LVOT/RVOT) (mm or cm)
timeFrame: Baseline and 3-months (endpoint)
measure: Left and right diastolic function (cm/s)
timeFrame: Baseline and 3-months (endpoint)
measure: Right ventricular fractional area change (RVFAC) (%)
timeFrame: Baseline and 3-months (endpoint)
measure: Left and right ventricle tissue doppler imaging (LVTDI/RVTDI) (cm/s)
timeFrame: Baseline and 3-months (endpoint)
measure: Left ventricle longitudinal, circumferential, and radial strain
timeFrame: Baseline and 3-months (endpoint)
measure: Left ventricle twist and untwist mechanics
timeFrame: Baseline and 3-months (endpoint)
measure: Right ventricle longitudinal strain
timeFrame: Baseline and 3-months (endpoint)
measure: Tricuspid annual plane systolic excursion (TAPSE) (mm)
timeFrame: Baseline and 3-months (endpoint)
measure: Fractional shortening (%)
timeFrame: Baseline and 3-months (endpoint)
Locations:
city: Nottingham
country: United Kingdom
facility: Nottingham Trent University
state: Nottinghamshire
city: Birmingham
country: United Kingdom
facility: Aston University
state: West Midlands
Study officials:
affiliation: Nottingham Trent University
name: Craig Sale, PhD
role: PRINCIPAL_INVESTIGATOR
References: