Arabinoxylan-oligosaccharides (AXOS) for the Management of Type-2 Diabetes

Study Overview
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Brief Summary
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The project aims to achieve significantly improved clinical care for type 2 diabetes. The current standard treatment metformin has low adherence due to its main side effect gut dysbiosis, which also results in more complications and high overall costs. Prebiotics have been suggested as a medical food and might be helpful as adjuvant management in type 2 diabetes and other metabolic diseases. Carbiotix AB has developed, a corn fiber extract containing arabinoxylan-oligosaccharides (AXOS), which have great potential for improving gut health. In this project, it will be investigated whether the intake of a hybrid product containing AXOS together with metformin can significantly improve glucose metabolism and gut health in patients with type 2 diabetes.

Detailed Description
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The prevalence of type 2 diabetes (T2D) is a high prevalence and the leading cause of death and disability worldwide. The quality of life is significantly decreased in these patients and the costs for medical care are enormous. T2D patients are often treated with metformin, but adherence to the treatment is relatively poor, with gut dysbiosis as a major cause. Gut dysbiosis has not been addressed in the clinical setting although numerous studies support its role in disease development. There is an urgent need to improve existing treatments with metformin to improve adherence to drug therapy and the management of the disease. Prebiotics are dietary fibers that stimulate the growth and activity of beneficial gut microbiota. Prebiotics has been suggested as a medical food and might be very useful as an effective adjuvant approach in the management of T2D and other metabolic diseases. Carbiotix AB, a biotech company based in Lund, has developed a corn fiber extract containing arabinoxylan-oligosaccharides (AXOS), which have great potential for improving gut health. In this project, a clinical trial will be performed to investigate whether the corn fiber extract can significantly increase metformin adherence with improved gut health and glucose metabolism in patients with T2D. To maximize the potential efficacy of the intervention, a Hybrid Product containing arabinogalactan (AG), xylan-oligosaccharides (XOS), and AXOS will be used, building on the XOS and AXOS naturally present in the corn fiber extract. One hundred subjects with T2D and treated with metformin will be recruited for this blind parallel randomized controlled intervention study. After a screening visit, the subjects will be randomized to test the Hybrid Product or placebo (maltodextrin) group. The duration of the intervention is 4 months, and the study subjects will be asked to consume the Hybrid Product or placebo daily (2x 5g). At the start, of week 8 and week 16, the study subjects will visit the study center for the measurement of body weight, waist circumference, and blood pressure. At these 3 visits, fasting blood samples are taken for analysis of glucose and insulin metabolism, blood lipids, and inflammation markers. Fecal samples are also collected to investigate the effect of the Hybrid Product on microbiota composition. At regular times during the study, the subjects must do a 7-point blood glucose monitoring and fill in questionnaires about gastrointestinal symptoms. During the whole study period, all subjects are contacted regularly to follow up on their health status. If the Hybrid Product shows the strong potential to improve adherence to metformin treatment, this will lead to improving diabetes care with reduced economic consequences. The promotion of a healthy gut by consumption of soluble fibers also helps to support immune function, blood sugar regulation, increased nutrient uptake (e.g. vitamin B12), and better body weight control. These health benefits will undoubtedly result in better well-being in private and working life and thus in a significantly improved quality of life for patients with T2D. Furthermore, effective treatment of T2D will also reduce the prevalence of cardiovascular risk factors, which are key targets in the current public health debate.

Official Title
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Arabinoxylan-oligosaccharides (AXOS) as a Medical Food for Adjuvant Approach in the Management of Type-2 Diabetes

Conditions
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Diabetes Type 2

Intervention / Treatment
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* Dietary Supplement: AG+XOS+AXOS
* Dietary Supplement: Placebo Maltodextrin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females with T2D and taking metformin as treatment for at least 6 months Age 50-80 years, at the time of signing the informed consent BMI 25-40 kg/m2 Stable body weight (less than 5% difference during the last 3 months) Willing and able to give written informed consent for participating the study Willing to comply with all study procedures Exclusion Criteria: Hba1c > 60 mmol/L fP-triglycerides > 4 mmol/ L - can be included if stabilized by medication fP total cholesterol >8 mmol/L - can be included if stabilized by medication high blood pressure >160/90 mmHg - can be included if stabilized by medication intake of antibiotics within 4 weeks prior to the start of the study regular intake of probiotics and/or prebiotics within 4 weeks prior to the start of the study alcohol abuse > 40g/d chronical disease (liver, kidney) gastrointestinal disease (ulcerative colitis, Crohn's disease, irritable bowel syndrome) heart disease (within the last 12 months) treatment with corticosteroids of significant degree psychological disease of significant degree cancer of significant degree gastric-bypass operation operation planned during the study period known gluten intolerance, lactose intolerance, milk protein allergy other food allergy special diet (e.g. vegetarian, vegan, LCHF, 5-2) non-Swedish speaking and reading investigator considers the subject unlikely to comply with the study procedures, restrictions, and requirements

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hybrid Product: Aarabinogalactan (AG)+xylan-oligosaccharides (XOS) +AXOS<br>Daily 2x 5g Hybrid Product, produced by Carbiotix AB. Hybrid Product is available as powder, which can be easily dissolved in water. | Dietary Supplement: AG+XOS+AXOS<br>* 4-month parallel randomized controlled study<br>|
| Placebo Comparator: Placebo<br>Daily 2x 5g maltodextrin. Maltodextrin is available as powder, which can be easily dissolved in water. | Dietary Supplement: Placebo Maltodextrin<br>* 4-month parallel randomized controlled study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in levels of postprandial blood glucose | Postprandial blood glucose will be analysed at the university hospital according to standard analytical procedures | 0, 2months and 4months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| gastrointestinal symptoms (bloating, abdominal pain, diarrhea, constipation) | Gastrointestinal symptoms will be measured using a questionnaire with a scale 0-5 | 0, 1months, 2months, 3months, 4months | 
| composition and activity of the gut microbiota (genus and species) | Fecal samples will be analysed to measure microbiota composition using high-throughput next-generation sequencing of 16S rRNA amplicons and quantitative PCR | 0, 2months and 4months | 
| levels of fasting blood glucose | Blood samples will be taken and analysed for glucose at the university hospital according to standard analytical procedures | 0, 2months and 4months | 
| level of Hba1c | Blood samples will be taken and analysed for Hba1c at the university hospital according to standard analytical procedures | 0, 2months and 4months | 
| blood lipid profile | Blood samples will be taken and analysed for total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides at the university hospital according to standard analytical procedures | 0, 2months and 4months | 
| immune functions | Blood samples will be taken and analysed for CRP at the university hospital according to standard analytical procedures | 0, 2months and 4months | 
| uptake of vitamin B12 and vitamin D | Blood samples will be taken and analysed for vitamin B12 and vitamin D at the university hospital according to standard analytical procedures | 0, 2months and 4months | 
| systolic and diastolic blood pressure | Systolic and diastolic blood pressure will be measured twice in sitting position using automatic devices | 0, 2months and 4months | 
| body weight | Body weight will be measured in kg to the nearest 0,1 kg using a digital scale | 0, 2months and 4months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AXOS, AG, XOS, metformin, gut microbiome, corn bran extract