Gfree - For Improved Blood Sugar and Reduced Inflammation.

Study Overview
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Brief Summary
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The goal of this clinical trial is to reduce inflammation and improve glycemic control in healthy volunteers, parents, as well as children, adolescents and adults with or without diabetes. The main questions it aims to answer are: • does a reduction wheat gluten improve glycemic control and/or inflammatory biomarkers • does a reduction in certain amino acids (which is most common in wheat gluten) improve glycemic control and/or inflammatory biomarkers • can we identify individuals with an inflammatory response, which leads to poor glycemic control. Participants will eat gluten-free products as well as similar products containing gluten. They will also eat gluten together with probiotics to see if an effect of gluten can be reduced. Researchers will compare everyone with themselves (cross-over design) and if possible individuals with and without diabetes.

Detailed Description
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BACKGROUND AND PURPOSE Many diseases, which are common in high-income countries, have an inflammatory component. In the world's rich countries, about 10% of the population will be diagnosed with a traditional inflammatory autoimmune disease during their lifetime. In an autoimmune disease, the body produces auto-antibodies against the body's own protein and the immune system destroys the body's own tissues. There are hundreds of different types of autoimmune diseases where some of the most common are; celiac disease (gluten intolerance), psoriasis, type 1 diabetes (T1D), multiple sclerosis, rheumatic diseases or thyroid diseases. Diseases such as cardiovascular disease, type 2 diabetes (T2D) and Alzheimer's disease are now also considered to have inflammatory components, and so-called auto-antibodies have been identified that indicate autoimmunity also in these diseases. Autoantibodies have also been identified in COVID-19 patients. To try to understand the biology behind autoimmunity and inflammatory disease, the investigators have analyzed the entire genome of patients with celiac disease as a model for autoimmunity. Celiac disease is a good so-called model disease for autoimmunity because the autoimmune reaction can be switched on and off with the help of gluten in the diet. With a strict gluten-free diet, virtually all signs of illness disappear and the inflammation ceases. The results from our whole genome analysis showed that genes involved in amino acid signaling were important for disease development and pointed to associations between celiac disease, T2D and anorexia. These results were somewhat surprising and the investigators began to look at the role of nutritional signaling and amino acids in inflammatory processes further. The purpose of this study is to test whether a reduction in certain amino acids (which is most common in wheat gluten) can improve glycemic control in healthy volunteers, parents, as well as children, adolescents and adults with diabetes and whether levels of inflammatory amino acids may be one of the factors behind the link between diabetes and severe COVID-19 infection. The participants will, for 4 weeks, eat one week as usual, eat one week wheat gluten-free, one week wheat gluten and one week with gluten and probiotics. The participants will be provided with continuous glucose monitors and activity-tracking bracelets. The investigators will analyze the efficiency of glucose uptake using continuous glucose monitors (CGM). During these four weeks, the research subjects will be admitted for 4 clinical visits (baseline, after 1 week, 2 weeks, 3 weeks) where blood samples will be taken. Also, during these weeks the participant will take capillary blood samples, faeces, urine, buccal swabs and saliva at home and fill out a questionnaire based on diet and risk factors for diabetes and questions about COVID-19. Total number of participants: 60 Sampling occasions per participant: 15 Follow-up period per participant: 4 weeks Number of years for inclusion: 2 years (20221201-20241201)

Official Title
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GFREE - A Study for Improved Blood Sugar Levels, Reduced Inflammation and for Increasing Knowledge of the Connection Between Diabetes and COVID-19.

Conditions
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Diabetes, Celiac Disease, Autoimmunity, Metabolic Disease

Intervention / Treatment
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* Dietary Supplement: gluten-free
* Dietary Supplement: probiotic
* Dietary Supplement: gluten


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - none Exclusion Criteria: - A diagnosis of celiac disease

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Four week crossover trial with three arms, gluten-free, gluten and gluten with probiotic
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: gluten-free<br>The study participants will start the gluten-free diet and be asked to exchange any products they normally buy with similar products. Three days in the week they will eat a meal with gluten free pasta. Two to six hours after the meal they will take samples at home and store until they return to the clinic. | Dietary Supplement: gluten-free<br>* see info in arm description<br>|
| Active Comparator: gluten<br>The study participants will continue the gluten-free diet and be asked to exchange any products they normally buy with similar products. Three days however, in the week they will eat a meal with regular gluten containing pasta. Two to six hours after the meal they will take samples at home and store until they return to the clinic. | Dietary Supplement: gluten-free<br>* see info in arm description<br>Dietary Supplement: gluten<br>* see info in arm description<br>|
| Active Comparator: probiotic<br>The study participants will continue the gluten-free diet and be asked to exchange any products they normally buy with similar products. During the week they will also take probiotic (Probion, Active) every morning and every evening. Three days however, in the week they will eat a meal with regular gluten containing pasta. Two to six hours after the meal they will take samples at home and store until they return to the clinic. | Dietary Supplement: gluten-free<br>* see info in arm description<br>Dietary Supplement: probiotic<br>* see info in arm description<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stabilizing of blood sugar levels | Continuous glucose monitoring (CGM) data will be analysed together with activity level data, lower glucose peaks after a meal, adjusted for activity level. | 0 days to 4 weeks | 
| Amino acid metabolism | Lowering of the aminoacid proline | 0 days to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Lipids | LDL, improved apolipoprotein B (APOB) | 0 days to 4 weeks | 
| Glutathione S Transferases | Relative Glutathione S Transferases expression levels | 0 days to 4 weeks | 
| Fibrinogen | Relative Fibrinogen expression levels | 0 days to 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gluten, probiotics, diet