Randomized, Cross-over Study Comparing the Effect of Two Alcohol-free Beers With Different Carbohydrates Composition on Lipid and Glycemic Metabolism in Subjects With Prediabetes and Recently Diagnosed Diabetes and Overweight or Obesity
Phase: NA
Conditions: Glucose Metabolism Disorders (Including Diabetes Mellitus), Overweight and Obesity
Sponsor: Instituto Aragones de Ciencias de la Salud

 
 
 
Study title: Randomized, cross-over study comparing the effect of two alcohol-free beers 
with different carbohydrates composition on lipid and glycemic metabolism in subjects 
with prediabetes and recently diagnosed diabetes and overweight or obesity.  
 
 
NCT number: Not yet assigned. 
 
 
 
Date of the document: 08/NOV/2017 
 

Title 
Randomized, cross-over study comparing the effect of two alcohol-free beers with 
different carbohydrates composition on lipid and glycemic metabolism in subjects with 
prediabetes and recently diagnosed diabetes and overweight or obesity.  
 
Brief title: Effect of two alcohol-free beers with different carbohydrates composition on 
lipids and glucose metabolism.  
 
Objective:  
Primary: To determine the effect of an alcohol-free beer with low glycemic index 
carbohydrates (isomaltulose) and a resistant maltodextrin, comparing to an alcohol-free 
beer with regular composition, on glycemic metabolism (glucose, glycated hemoglobin, 
insulin and HOMA index) in subjects with recently diagnosed diabetes mellitus and 
overweight or obesity.  
Secondary: To determine the effect of an alcohol-free beer with low glycemic index 
carbohydrates (isomaltulose) and a resistant maltodextrin, comparing to an alcohol-free 
beer with regular composition, on: a) lipid profile (total cholesterol, LDL cholesterol, 
HDL cholesterol, triglycerides and apolipoproteins A and B); b) body weight and waist 
circumference; c) inflammatory biomarkers (C reactive protein); d) intestinal microbiota 
in a subgroup of participants.  
 
Inclusion criteria: 
- Aged between 18 and 80 years. 
- To provide informed consent in writing of voluntary participation in the study after 
having read the participant information sheet, and having consulted the doubts that may 
arise from it. 
- Diagnosis of prediabetes or diabetes mellitus type 2 defined as: a) fasting glucose ≥ 100 
mg/dL in the last 3 months; b) glycated hemoglobin ≥ 5.7% and ≤ 6.5%. 

Exclusion criteria: 
- 
Gluten intolerance.  
- 
Taking lipid-lowering drugs. 
- 
Taking antidiabetic drugs, except for metformin in a stable dose in the last 3 months. 
- 
To be under treatment with insulin. 
- 
Presence of uncontrolled endocrinological disease by including hypothyroidism. 
- 
Regular intake of functional foods with plant sterols in the past 6 weeks. 
- 
Intake of vitamin supplements. 
- 
Hormone replacement therapy. 
- 
High intake of alcohol (> 30 g ethanol) on a regular basis. 
- 
Pregnancy or intention of pregnancy during the study since the proposed nutritional 
intervention may not be suitable for this situation. 
- 
Serious illness of any type with less than 1-year life expectancy or if, in the opinion 
of the investigators, it would limit a stable diet throughout the study. 
- 
To be under treatment with corticosteroids, hormonal treatment or antibiotics the 3 
months prior to randomization. 
- 
To take prebiotics, probiotics, vitamin supplements and any other drug that could 
influence the intestinal microbiota, in the 3 months prior to randomization. 
- 
Any other circumstances which, according to researcher’ s assessment, could interfere 
with the correct development of nutritional intervention (e.g.: frequent trips during 
the study, failure to attend visits by personal or business circumstances, etc.). 
 
Brief Summary: 
This a controlled, double-blind, randomized, cross designed study to determine the effect 
of an alcohol-free beer with low glycemic index carbohydrates (isomaltulose) and a 
resistant maltodextrin, comparing to an alcohol-free beer with regular composition, on 
glycemic metabolism (glucose, glycated hemoglobin, insulin and HOMA index) in 
subjects with recently diagnosed diabetes mellitus and overweight or obesity. We include 
44 subjects who are randomized to consume for 10 weeks: a) two alcohol-free beers with 
regular carbohydrates composition per day; b) two alcohol-free beers with modified 
carbohydrates composition per day. Those subjects randomized to begin with A beer 

during 10 weeks will change to B beer during the second phase for 10 weeks and vice 
versa. There is a 4-8 weeks wash-out period between two phases.  
 
Study Detailed Description: 
The study involves a nutritional intervention with a controlled, double-blind, randomized, 
cross design. It includes 44 healthy subjects with a total duration of 20 weeks with a 
"wash-out/stabilization" period for 2-4 weeks before randomization. Subjects are 
randomized in two groups: (1) those who begin drinking 2 alcohol-free beers (33 cl each 
one) that are enriched in a resistant maltodextrin and isomaltulose during 10 weeks and 
continue drinking 2 alcohol-free beers (33 cl each one) with regular composition during 
the next 10 weeks following; (2) those who will follow the same previous intervention 
but in reverse, beginning with standard alcohol-free beer for 10 weeks, followed by 
resistant maltodextrin and isomaltulose-enriched beer for the remaining 10 weeks. There 
is a washout period between both phases to facilitate adherence to nutritional intervention, 
since we consider that a period of 20 consecutive weeks could be difficult to assume for 
the participants. Participants and the research team are "blind" to the type of beer that 
subjects are taking in each phase. Only one person of the company that provide beers, 
which does not directly participate in the clinic visits or in the analysis of the data, is 
aware of this information. Clinical staff performed the randomization based on a 
computerized method.   
Among those subjects included in the study, microbiota sub-study is proposed which 
require a specific authorization within informed consent. Among all subjects that are 
included in this substudy and that have completed the whole nutritional intervention, 10 
subjects (5 from each randomized group) will be selected to microbiota determination.  
 
Study visits: 
1. Prescreening visit: Inclusion and exclusion criteria assessment and blood collection if 
glucose or glycated hemoglobin is not available in previous 3 months. Healthy dietary 
and physical activity counselling is provided by a nutritionist; it should be maintained 
during all study. Baseline visit is scheduled in 2-4 weeks after lifestyle stabilization.  

2. Baseline phase 1 visit: Clinical, biochemical, dietary, physical activity and 
anthropometric data are assessed. Computer-based randomization is performed. 
Alcohol-free beer (A or B according to randomization procedures) for the next 10 
weeks is delivered to the participant who has to consume two per day. A nutritionist 
emphasizes healthy lifestyle counselling to the participant. A feces sample is collected 
if subjects accept to be included in microbiota sub study.  
3. Intermediate phase 1 visit: Clinical, biochemical, dietary, physical activity and 
anthropometric data are assessed. Satiety after alcohol-free beer consumption is 
measured by a validated questionnaire. A nutritionist emphasizes healthy lifestyle 
counselling to the participant.  
4.  End of phase 1 visit: Clinical, biochemical, dietary, physical activity and 
anthropometric data are assessed. Satiety after alcohol-free beer consumption is 
measured by a validated questionnaire. A nutritionist emphasizes healthy lifestyle 
counselling to the participant. A wash-out period of 4-8 weeks is scheduled before the 
next phase start. A feces sample is collected if subjects accept to be included in 
microbiota sub study. 
5. Baseline phase 2 visit: Clinical, biochemical, dietary, physical activity and 
anthropometric data are assessed. Alcohol-free beer (A or B: if subjects consumed 
alcohol-free beer A, he/she change to alcohol-free B and vice versa) for the next 10 
weeks is delivered to the participant who has to consume two per day. A nutritionist 
emphasizes healthy lifestyle counselling to the participant. A feces sample is collected 
if subjects accept to be included in microbiota sub study. 
6. Intermediate phase 2 visit: Clinical, biochemical, dietary, physical activity and 
anthropometric data are assessed. Satiety after alcohol-free beer consumption is 
measured by a validated questionnaire. A nutritionist emphasizes healthy lifestyle 
counselling to the participant.  
7. End of phase 2 visit: Clinical, biochemical, dietary, physical activity and 
anthropometric data are assessed. Satiety after alcohol-free beer consumption is 
measured by a validated questionnaire. A nutritionist emphasizes healthy lifestyle 
counselling to the participant. A feces sample is collected if subjects accept to be 
included in microbiota sub study. 
 
 

Study variables: 
- 
Clinical variables: Gender, age, medical records including diseases and medication, 
tobacco consumption and blood pressure. 
- 
Anthropometric variables: Weight, height, body mass index, waist circumference, 
body composition analysis. 
- 
Biochemical variables: Glucose, lipid and iron metabolism are assessed. 
Inflammatory biomarkers, including C reactive protein, are also determined.  
- 
Microbiota: Feces samples are collected to microbiota analysis including Bacteroides, 
Lactobacillus, Enterococcus, Prevotella or Roseburia, among others. 
- 
Dietary and physical activity assessment: Diet and physical activity are assessed by 
validated questionnaires.  
 
Informed consent 
All participants must sign a consent before entering the study. Informed consent is 
obtained by one of the researchers of the study after the patient has carefully reviewed 
the information sheet which explains the objectives, methodology, benefits and 
disadvantages of intervention. The participant is encouraged to ask for any doubt he/she 
has regarding the study before signing the informed consent. Informed consent includes 
a section where participant has to indicate if he/she wants to participate in the microbiota 
substudy. If they do not accept, they are included in the study if meeting eligibility 
criteria, but feces samples are not collected in corresponding visits.  
The study, including protocol, informed consent, information sheet and other documents, 
has been approved by the Ethical Committee of Clinical Research of Aragon (CEICA).  
 
Statistical analysis plan 
The sample size was established by taking as main outcome variable the change of 
glucose concentration, whose clinical variability is estimated at 16 mg/dL in pre-diabetic 
population. This is the estimated value based on the epidemiological study carried out in 
Spanish population (PREDIMED) (Estruch R et al. N Engl J Med 2013;368:1279-90). It 
was expected to find a difference of 12 mg/dL in glucose levels between two intervention 

arms. It was established a confidence level (1-α) of 95% (bilateral Zα = 1,960) and 90% 
of statistical power (1 – β) (bilateral Zβ = 1,282), by obtaining a sample size of 37 
subjects. It was estimated a 25% loss rate, so final sample was 44 subjects. 
Different alcohol-free beers effects on study outcomes will ve evaluated by repeated 
measures ANOVA or the Friedman test, as appropriate. When significant differences are 
detected, multiple comparisons will be made by using the Bonferroni correction for 
normally distributed variables or the Wilcoxon test for paired samples for variables with 
a skewed distribution. Treatment order will be entered in all models as an additional 
factor. Data will be presented as means (±SD) for continuous variables or medians and 
interquartile ranges (IR) for those with a skewed distribution). Statistical analysis will be 
processed using the software SPSS (version 24.0; SPSS, Chicago, Illinois, USA), using a 
significance level of P < 0,05.