Clinical trial NCT05689684: Arabinoxylan-oligosaccharides (AXOS) for the Management of Type-2 Diabetes
Official title: Arabinoxylan-oligosaccharides (AXOS) As a Medical Food for Adjuvant Approach in the Management of Type-2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Type 2
Keywords: AXOS
AG
XOS
metformin
gut microbiome
corn bran extract
Lead sponsor: Lund University
Sponsor class: OTHER
Collaborators: name: Carbiotix AB
name: Skane University Hospital
name: Vinnova
First posted: 2023-01-19
Enrollment: 66
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: change in levels of postprandial blood glucose
timeFrame: 0, 2months and 4months
Secondary outcomes:
measure: gastrointestinal symptoms (bloating, abdominal pain, diarrhea, constipation)
timeFrame: 0, 1months, 2months, 3months, 4months
measure: composition and activity of the gut microbiota (genus and species)
timeFrame: 0, 2months and 4months
measure: levels of fasting blood glucose
timeFrame: 0, 2months and 4months
measure: level of Hba1c
timeFrame: 0, 2months and 4months
measure: blood lipid profile
timeFrame: 0, 2months and 4months
measure: immune functions
timeFrame: 0, 2months and 4months
measure: uptake of vitamin B12 and vitamin D
timeFrame: 0, 2months and 4months
measure: systolic and diastolic blood pressure
timeFrame: 0, 2months and 4months
measure: body weight
timeFrame: 0, 2months and 4months
Other outcomes:
Locations:
city: Lund
country: Sweden
facility: Biomedical Nutrition, Lund University and Department of Endocrinology , Lund University Hospital
Study officials:
affiliation: Lund University
name: Lieselotte Cloetens
role: PRINCIPAL_INVESTIGATOR
References:
citation: Boll EV, Ekstrom LM, Courtin CM, Delcour JA, Nilsson AC, Bjorck IM, Ostman EM. Effects of wheat bran extract rich in arabinoxylan oligosaccharides and resistant starch on overnight glucose tolerance and markers of gut fermentation in healthy young adults. Eur J Nutr. 2016 Jun;55(4):1661-70. doi: 10.1007/s00394-015-0985-z. Epub 2015 Jul 14.
citation: Cloetens L, Broekaert WF, Delaedt Y, Ollevier F, Courtin CM, Delcour JA, Rutgeerts P, Verbeke K. Tolerance of arabinoxylan-oligosaccharides and their prebiotic activity in healthy subjects: a randomised, placebo-controlled cross-over study. Br J Nutr. 2010 Mar;103(5):703-13. doi: 10.1017/S0007114509992248. Epub 2009 Dec 10.
citation: Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, Scott K, Stanton C, Swanson KS, Cani PD, Verbeke K, Reid G. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017 Aug;14(8):491-502. doi: 10.1038/nrgastro.2017.75. Epub 2017 Jun 14.
citation: McGovern A, Tippu Z, Hinton W, Munro N, Whyte M, de Lusignan S. Comparison of medication adherence and persistence in type 2 diabetes: A systematic review and meta-analysis. Diabetes Obes Metab. 2018 Apr;20(4):1040-1043. doi: 10.1111/dom.13160. Epub 2017 Dec 12.
citation: Uusitupa M, Khan TA, Viguiliouk E, Kahleova H, Rivellese AA, Hermansen K, Pfeiffer A, Thanopoulou A, Salas-Salvado J, Schwab U, Sievenpiper JL. Prevention of Type 2 Diabetes by Lifestyle Changes: A Systematic Review and Meta-Analysis. Nutrients. 2019 Nov 1;11(11):2611. doi: 10.3390/nu11112611.